Myeloperoxidase Activity (myeloperoxidase + activity)

Distribution by Scientific Domains
Distribution within Medical Sciences

Selected Abstracts

The role of erythropoietin in the protection of gastric mucosa from indometacin-induced gastric injury and its relationship with oxidant and antioxidant parameters in rats

Fatih Albayrak
Abstract Objectives Erythropoietin has anti-oxidative and anti-inflammatory activity. We wanted to evaluate its activity in preventing damage to the gastric mucosa. Methods We examined the protective effect of erythropoietin on indometacin-induced gastric mucosa damage in the rat stomach and compared its potency with that of famotidine. We also measured effects on oxidant and antioxidant parameters in the rat stomach. Key findings Famotidine and erythropoietin 2500 and 5000 IU/kg reduced the ulcer area by 98%, 31% and 58%, respectively, compared with the indometacin group. Superoxide dismutase activity and glutathione level were decreased and myeloperoxidase activity increased in the indometacin group compared with healthy rats. Famotidine and erythropoietin at all doses increased superoxide dismutase and glutathione levels significantly compared with the indometacin group. Myeloperoxidase activity was decreased by erythropoietin and famotidine. Conclusions These results support the view that erythropoietin counteracts the effects of indometacin in inducing gastric ulcer and could be used as a an antiulcer compound. Its antiulcer effect is less potent than that of famotidine. The antiulcerogenic effects of erythropoietin may be related to its intrinsic ability to sustain the activities of free-radical scavenging enzymes and the bioavailability of glutathione. [source]

FR183998, a Na+/H+ exchange inhibitor, suppresses both IL-8 content and myocardial infarct size in a cardiac ischaemia-reperfusion model in rats

F. Ohara
The aim of this study was to determine the effect of FR183998 (5-(2,5-dichlorothiophen-3-yl)-3-[(2-dimethylaminoethyl)carbamoyl]benzoylguanidine dihydrochloride), an Na+/H+ exchange inhibitor, on myocardial interleukin-8 (IL-8) content and myocardial infarct size in a rat ischaemia and reperfusion model. Rats underwent30 min of ischaemia followed by 1 to 24 h of reperfusion. IL-8 content rapidly increased in reperfused rat hearts. The maximum increase in IL-8 was obtained after 3 h of reperfusion. Intravenous administration of FR183998 at 1 and 3.2 mg kg,1, 5 min before ischaemia, significantly reduced the IL-8 level after 3 h of reperfusion (122 ± 16 and 149 ± 23 pg mg,1 protein, respectively), compared with that of the saline-treated group (258 ± 27 pg mg,1 protein). Myeloperoxidase activity after 3 h of reperfusion was also reduced by FR183998 (from 0.83 ± 0.19 unit g,1 weight of tissue in the saline-treated group to 0.36 ± 0.09 and 0.33 ± 0.06 unit g,1 weight of tissue in FR183998-treated groups at 1.0 and 3.2 mg kg,1, respectively). Myocardial infarction induced by 30 min of ischaemia and 24 h of reperfusion was significantly suppressed by the same doses of FR183998 (14.0 ± 1.5,13.5 ± 1.9% at 1.0 and 3.2 mg kg,1), compared with 22.2 ± 2.7% in the saline-treated group. These results suggest that IL-8 may contribute to the generation of myocardial infarction in an ischaemia and reperfusion model in rats. [source]

Baicalin attenuates air embolism-induced acute lung injury in rat isolated lungs

Min-Hui Li
Background and purpose:, Baicalin has been reported to have anti-inflammatory effects and protect against various tissue injuries. However, the effect of baicalin on air embolism-induced acute lung injury has not been tested yet. Experimental approach:, Acute lung injury was induced by infusion of air at a rate of 0.25 mL·min,1 for 1 min into the pulmonary artery of rat isolated lungs. At the end of the experiment, samples were collected for assessment of lung injury, biochemical analysis and histology. Different doses of baicalin (1, 2 and 4 mg·kg,1) were given into the perfusate before air infusion. Key results:, Air embolism elicited a significant increase in microvascular permeability (Kf), lung weight gain, wet/dry weight ratio, pulmonary artery pressure and protein concentration in the bronchoalveolar lavage fluid. Levels of the cytokines, tumour necrosis factor , and cytokine-induced neutrophil chemoattractant-1 in perfusate, and malondialdehyde levels and myeloperoxidase activities in lung tissue were also significantly increased. In addition, histological examination showed increased neutrophil infiltration in lung tissues. Furthermore, nuclear factor-,B activity and degradation of I,B-, were significantly increased in lungs. Pretreatment of the lungs with baicalin (4 mg·kg,1) showed a statistically significant difference in all of the assessed parameters, except for alteration in the pulmonary artery pressure. Conclusions and implications:, Our study suggests that baicalin attenuated air embolism-induced acute lung injury and may be considered a useful adjunct drug therapy in this clinical condition. [source]

Effects of a selective Rho-kinase inhibitor Y-27632 on oxidative stress parameters in acute dichlorvos poisoning in rats

N. Gunay
Abstract This study examined the effects of Y-27632, a selective Rho-kinase inhibitor, on organophosphate-induced acute toxicity in rats. Rats were randomly divided into four groups as control (corn oil), dichlorvos (30,mg,kg,1 i.p.), 1 and 10,mg,kg,1 Y-27632,+,dichlorvos groups. Cholinergic signs (fatigue, tremor, cyanosis, hyper-secretion, fasciculations) were observed in all the rats in the dichlorvos group and the mortality rate was 50%. No cholinergic findings and deaths were observed in the control and Y-27632 groups. Plasma cholinesterase activities were suppressed with dichlorvos and these reductions were attenuated with Y-27632 pretreatment. There was a marked increase in plasma malondialdehyde level in the dichlorvos group, but Y-27632 pretreatment abolished this elevation. Dichlorvos markedly depressed cardiac paraoxonase activity, but these changes were not markedly modified with Y-27632. Total antioxidant capacities, total oxidant status, oxidative stress index, total free sulfhydryl groups and catalase activities in plasma and cardiac tissues were not markedly different between the groups. No significant changes were observed with cardiac myeloperoxidase activities or plasma arylesterase and ceruloplasmin activities. In conclusion, our results suggest that Rho-kinase pathway is involved in organophosphate intoxication, and a decrease in cardiac paraoxonase activities may play a role in the pathogenesis of acute organophosphate poisoning in rats. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Protective effect of curcumin, a Curcuma longa constituent, in early colonic inflammation in rats,

Juan Manuel Sánchez-Calvo
Abstract Curcumin, a polyphenol derived from the plant, Curcuma longa, has a variety of pharmacological effects, including chemotherapeutic, anti-inflammatory, antiangiogenic, and antioxidant activities. To gain a better understanding of the effects and mechanisms of action of curcumin on the acute injury caused by intra-colonic administration of acetic acid (AA) in rats, inflammation was assessed by histology and myeloperoxidase activity (MPO; an index of neutrophil infiltration in the mucosa); Th1 and Th2 cytokine production; histological and histochemical analysis of the lesions; nitrite production in colon mucosa; and the expression of iNOS, COX-1 and -2 using Western blotting and inmmunohistochemistry. We also studied the involvement of the p38 MAPK/JNK signalling pathway in the protective effect of curcumin in acute colonic inflammation. Curcumin (50,100,mg/kg/day) reduced the degree of colonic injury, the index of neutrophil infiltration and Th1 cytokine secretion, and increased IL-10 production, reduced colonic levels of nitrites, and reduced COX-2 and iNOS overexpression. A reduction in the activation of p38 and JNK MAPKs was also observed. Thus, we show that the widely used food additive, curcumin reduced the development of AA-induced colitis and alleviated the inflammatory response. Inhibition of MAPK signalling by curcumin could explain the changes on the cytokine Th1/Th2 profile, the reduction of COX-2 and iNOS signaling, as well as the decreased nitrite production in colonic mucosa, suggesting that curcumin may be useful in the treatment of ulcerative colitis. Drug Dev Res, 2009. © 2009 Wiley-Liss, Inc. [source]

Role of osteopontin in neutrophil function

IMMUNOLOGY, Issue 4 2007
Adeline Koh
Summary Osteopontin (OPN) is important for the function of fibroblasts, macrophages and lymphocytes during inflammation and wound healing. In recent studies of experimental colitis we demonstrated exacerbated tissue destruction in OPN-null mice, associated with reduced tumour necrosis factor-, expression and increased myeloperoxidase activity. The objective of this investigation therefore was to determine the importance of OPN expression in neutrophil function. Although, in contrast to macrophages, neutrophils expressed low levels of OPN with little or no association with the CD44 receptor, intraperitoneal recruitment of neutrophils in OPN-null mice was impaired in response to sodium periodate. The importance of exogenous OPN for neutrophil recruitment was demonstrated by a robust increase in peritoneal infiltration of PMNs in response to injections of native or recombinant OPN. In vitro, OPN,/, neutrophils exhibited reduced chemokinesis and chemotaxis towards N -formyl methionyl leucyl phenylalanine (fMLP), reflecting a reduction in migration speed and polarization. Exogenous OPN, which was chemotactic for the neutrophils, rescued the defects in polarization and migration speed of the OPN,/, neutrophils. In contrast, the defensive and cytocidal activities of OPN,/, neutrophils, measured by assays for phagocytosis, generation of reactive oxygen species, cytokine production and matrix metalloproteinase-9, were not impaired. These studies demonstrate that, while exogenous OPN may be important for the recruitment and migration of neutrophils, expression of OPN by neutrophils is not required for their destructive capabilities. [source]

Activation of the cannabinoid 2 receptor (CB2) protects against experimental colitis

Martin A. Storr MD
Abstract Background: Activation of cannabinoid (CB)1 receptors results in attenuation of experimental colitis. Our aim was to examine the role of CB2 receptors in experimental colitis using agonists (JWH133, AM1241) and an antagonist (AM630) in trinitrobenzene sulfonic acid (TNBS)-induced colitis in wildtype and CB2 receptor-deficient (CB mice. Methods: Mice were treated with TNBS to induce colitis and then given intraperitoneal injections of the CB2 receptor agonists JWH133, AM1241, or the CB2 receptor antagonist AM630. Additionally, CB mice were treated with TNBS and injected with JWH133 or AM1241. Animals were examined 3 days after the induction of colitis. The colons were removed for macroscopic and microscopic evaluation, as well as the determination of myeloperoxidase activity. Quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) for CB2 receptor was also performed in animals with TNBS and dextran sodium sulfate colitis. Results: Intracolonic installation of TNBS caused severe colitis. CB2 mRNA expression was significantly increased during the course of experimental colitis. Three-day treatment with JWH133 or AM1241 significantly reduced colitis; AM630 exacerbated colitis. The effect of JWH133 was abolished when animals were pretreated with AM630. Neither JWH133 nor AM1241 had effects in CB mice. Conclusions: We show that activation of the CB2 receptor protects against experimental colitis in mice. Increased expression of CB2 receptor mRNA and aggravation of colitis by AM630 suggests a role for this receptor in normally limiting the development of colitis. These results support the idea that the CB2 receptor may be a possible novel therapeutic target in inflammatory bowel disease. (Inflamm Bowel Dis 2009) [source]

Proteinase-activated receptor-1 is an anti-inflammatory signal for colitis mediated by a type 2 immune response

Nicolas Cenac PhD
Abstract Background: Activation of colonic proteinase activated receptor-1 (PAR1) provokes colonic inflammation and increases mucosal permeability in mice. The mechanism of inflammation is not neurogenic like in the paw of rats but depends on PAR1 -mediated activation monocytic cells. PAR1 activation in the colon increases the release of lymphocyte T helper-1 (TH1) cytokines. Moreover, PAR1 expression is increased in biopsies from patients with inflammatory bowel disease, and its activation during TH1-mediated colitis in mice increases all of the hallmarks of inflammation. Methods: This study aimed to characterize the effects of PAR1 activation in oxazolone-mediated colitis, involving a TH2 cytokine profile. Results: Intracolonic administration of oxazolone increased myeloperoxidase activity, damage score, and interleukin (IL)-4, IL-10, tumor necrosis factor ,, and IL-1, mRNA expression but lowered interferon-, mRNA expression, indicating colonic inflammation of a TH2 profile. The concurrent intracolonic administration of a PAR1 agonist in oxazolone-treated mice inhibited colitis, resulting in a reduction of myeloperoxidase activity, damage score, and inflammatory cytokine mRNA expression. Using PAR1 -deficient mice, we confirmed that the anti-inflammatory effects of PAR1 agonists were mediated by PAR1. Moreover, in PAR1 -deficient mice or in mice treated with a PAR1 antagonist, oxazolone-induced colitis was exacerbated, showing an endogenous modulatory role for PAR1 in this TH2 cytokine profile of colitis. Conclusions: Thus, as opposed to a previously shown proinflammatory role for PAR1 in a TH1 cytokine-mediated colitis, our new data show anti-inflammatory role for PAR1 activation in the setting of TH2 cytokine colitis model. [source]

Gliotoxin, an inhibitor of nuclear factor-kappa B, attenuates peptidoglycan-polysaccharide-induced colitis in rats

Dr. Leo R. Fitzpatrick
Abstract Gliotoxin is a fungal metabolite that has immunosuppressive properties. First, we determined if gliotoxin could inhibit bacterial peptidoglycan,polysaccharide-stimulated tumor necrosis factor-, production, as well as nuclear factor-kappa B (NF-,B), in a rat macrophage (NR8383) cell line. Next, the apoptosis-inducing potential of gliotoxin was also evaluated in this cell line. Finally, we evaluated whether gliotoxin could reduce peptidoglycan,polysaccharide-induced colitis in rats. Gliotoxin (2 mg/kg/day) was dosed from day 14 after the initial intramural colonic injection of peptidoglycan,polysaccharide until day 21. A gross colonic injury score, myeloperoxidase activity, and cytokine levels were all evaluated on day 21. Gliotoxin dose dependently inhibited cytokine production, as well as NF-,B, and also induced apoptosis in the NR8383 cell line. On day 21, gliotoxin significantly reduced gross colonic injury (adhesions, nodules, mucosal lesions) in rats. Gliotoxin-treated rats also had partially normalized biochemical indices of colitis, such as colonic cytokine levels. The colonic level of NF-,B was also partially normalized in gliotoxin treated rats. Gliotoxin also exhibited an antiarthritis effect in peptidoglycan,polysaccharide-treated rats. In summary, gliotoxin effectively attenuated the chronic reactivation phase of peptidoglycan,polysaccharide-induced colitis. This anticolitis effect may be related to the inhibition of NF-,B in Lewis rats. [source]

Hydroquinone and its analogues in dermatology , a potential health risk

W Westerhof
Summary Hydroquinone has been used for decades as a skin lightening agent. Since January 1, 2001, its use in cosmetics has been banned. This ban is as a result of mid-term effects such as leukoderma-en-confetti/occupational vitiligo and exogenous ochronosis. However, a recent literature search on hydroquinone as a skin lightening agent suggests that possible long-term effects such as carcinogenesis may be expected as well. Metabolites of hydroquinone formed in the liver, e.g., p-benzoquinone and glutathione conjugates of hydroquinone, are mainly responsible for this. In the bone marrow, hydroquinone is oxidized into p-benzoquinone because of the high myeloperoxidase activity. Topically applied hydroquinone-containing creams may give rise to accumulation of these compounds, which can cause DNA damage and mutations. They also have the capability to disrupt protective mechanisms, whereby they facilitate further development of cancer. In the bone marrow, long-term effects such as aplastic anemia and acute myeloid leukemias may occur. Most of the evidence stems from research on benzene toxicity, which appears to arise via its metabolite hydroquinone. There is no report yet demonstrating carcinogenesis resulting from the application of hydroquinone-containing creams. However doctors should be aware of these potential health risks which were up until now disregarded. [source]

The role of erythropoietin in the protection of gastric mucosa from indometacin-induced gastric injury and its relationship with oxidant and antioxidant parameters in rats

Fatih Albayrak
Abstract Objectives Erythropoietin has anti-oxidative and anti-inflammatory activity. We wanted to evaluate its activity in preventing damage to the gastric mucosa. Methods We examined the protective effect of erythropoietin on indometacin-induced gastric mucosa damage in the rat stomach and compared its potency with that of famotidine. We also measured effects on oxidant and antioxidant parameters in the rat stomach. Key findings Famotidine and erythropoietin 2500 and 5000 IU/kg reduced the ulcer area by 98%, 31% and 58%, respectively, compared with the indometacin group. Superoxide dismutase activity and glutathione level were decreased and myeloperoxidase activity increased in the indometacin group compared with healthy rats. Famotidine and erythropoietin at all doses increased superoxide dismutase and glutathione levels significantly compared with the indometacin group. Myeloperoxidase activity was decreased by erythropoietin and famotidine. Conclusions These results support the view that erythropoietin counteracts the effects of indometacin in inducing gastric ulcer and could be used as a an antiulcer compound. Its antiulcer effect is less potent than that of famotidine. The antiulcerogenic effects of erythropoietin may be related to its intrinsic ability to sustain the activities of free-radical scavenging enzymes and the bioavailability of glutathione. [source]

Mechanisms of protection by melatonin against acetaminophen-induced liver injury in mice

Tatsuya Matsura
Abstract:, The present study was performed to determine whether melatonin protects mouse liver against severe damage induced by acetaminophen (APAP) administration and where melatonin primarily functions in the metabolic pathway of APAP to protect mouse liver against APAP-induced injury. Treatment of mice with melatonin (50 or 100 mg/kg, p.o.) 8 or 4 hr before APAP administration (750 mg/kg, p.o.) suppressed the increase in plasma alanine aminotransferase and aspartate aminotransferase activities in a dose- and a time-dependent manner. Melatonin treatment (100 mg/kg, p.o.) 4 hr before APAP administration remarkably inhibited centrilobular hepatic necrosis with inflammatory cell infiltration and increases in hepatic lipid peroxidation and myeloperoxidase activity, an index of tissue neutrophil infiltration, as well as release of nitric oxide and interleukin-6 into blood circulation at 9 hr after APAP administration. However, melatonin neither affected hepatic reduced glutathione (GSH) content nor spared hepatic GSH consumption by APAP treatment. Moreover, pretreatment with melatonin 4 hr before APAP administration did not influence the induction of hepatic heat shock protein 70 (HSP70) by APAP and melatonin alone did not induce HSP70 in mouse liver. These results indicate that exogenously administered melatonin exhibits a potent hepatoprotective effect against APAP-induced hepatic damage probably downstream of the activity of cytochrome P450 2E1, which works upstream of GSH conjugation in the pathway of APAP metabolism, via its anti-nitrosative and anti-inflammatory activities in addition to its antioxidant activity. [source]

Melatonin protects against pressure ulcer-induced oxidative injury of the skin and remote organs in rats

Abstract:, Pressure ulcers (PU) cause morphological and functional alterations in the skin and visceral organs; the damage is believed to be due to ischemia/reperfusion (I/R) injury. In this study, we examined the role of oxidative damage in PU and the beneficial effect of treatment with the antioxidant melatonin. PU were induced by applying magnets over steel plates that were implanted under the skin of rats; this compressed the skin and caused ischemia. Within a 12-hr period, rats were subjected to five cycles of I/R (2 and 0.5 hr respectively), followed by an additional 12 hr of ischemia (to simulate the period at sleep at night). This protocol was repeated for 3 days. In treatment groups, twice a day during reperfusion periods, melatonin (5 mg per rat) was either applied locally as an ointment on skin, or administered i.p. (10 mg/kg). At the end of the experimental period, blood and tissue (skin, liver, kidney, lung, stomach, and ileum) samples were taken for determination of biochemical parameters and for histological evaluation. Local treatment with melatonin inhibited the increase in malondialdehyde levels; an index of lipid peroxidation, myeloperoxidase activity; an indicator of tissue neutrophil infiltration, and the decrease in glutathione; a key antioxidant, in the skin induced by PU, but was less efficient in preventing the damage in visceral organs. However, systemic treatment prevented the damage in the visceral organs. Significant increases in creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and collagen levels in animals with PU were prevented by melatonin treatment. The light microscopic examination exhibited significant degenerative changes in dermis and epidermis in the PU rats. Tissue injury was decreased especially in the locally treated group. Findings of the present study suggest that local and/or systemic melatonin treatment may prove beneficial in the treatment of PU. [source]

Melatonin treatment protects against ischemia/reperfusion-induced functional and biochemical changes in rat urinary bladder

Göksel, ener
Abstract: Reactive oxygen metabolites play important roles in ischemia/reperfusion (I/R) injury in several systems. The aim of this study was to investigate the role of melatonin against I/R injury of the rat urinary bladder. The abdominal aorta was clamped to induce ischemia for 30 min, then the animals were subjected to 60 min of reperfusion. Melatonin (10 mg/kg, i.p.) or the vehicle (control 1% alcohol i.p.) was administered before I/R. After decapitation, the bladder was removed and the tissue was either used for functional studies or stored for measurement of products of lipid peroxidation (LP), glutathione (GSH) levels and myeloperoxidase activity (MPO). Bladder strips were suspended in oxygenated Tyrode's buffer at 37°C and isometric contractions to carbachol (CCh; 10,8,10,4 m) were recorded. In the I/R group, the contractile responses of the bladder strips were lower than those of the control group (P < 0.01,0.001) and were reversed by treatment with melatonin (P < 0.05,0.001). LP which was higher in I/R group compared with control (27.68 ± 1.69 and 10.59 ± 1.27 nmol/g, respectively; P < 0.001) was partially reversed by melatonin (19.01 ± 1.85 nmol/g; P < 0.01). Similarly, GSH showed a decrease in the I/R group compared with controls (0.27 ± 0.03 and 0.43 ± 0.04 ,mol/g, respectively; P < 0.05) and melatonin prevented this effect completely (0.45 ± 0.04 , mol/g; P < 0.05). MPO activity in the I/R group (4.19 ± 0.08 U/g) was significantly higher than that of the control group (1.41 ± 0.08 U/g; P < 0.001) and melatonin treatment reduced MPO levels compared with I/R alone (3.16 ± 0.07; P < 0.001). Melatonin almost completely reversed the low contractile responses of rat urinary bladder strips to CCh and prevented oxidative tissue damage following I/R. [source]

Nitric Oxide-Mediated Intestinal Injury Is Required for Alcohol-Induced Gut Leakiness and Liver Damage

ALCOHOLISM, Issue 7 2009
Yueming Tang
Background:, Alcoholic liver disease (ALD) requires endotoxemia and is commonly associated with intestinal barrier leakiness. Using monolayers of intestinal epithelial cells as an in vitro barrier model, we showed that ethanol-induced intestinal barrier disruption is mediated by inducible nitric oxide synthase (iNOS) upregulation, nitric oxide (NO) overproduction, and oxidation/nitration of cytoskeletal proteins. We hypothesized that iNOS inhibitors [NG-nitro- l -arginine methyl ester (l -NAME), l -N6 -(1-iminoethyl)-lysine (l -NIL)] in vivo will inhibit the above cascade and liver injury in an animal model of alcoholic steatohepatitis (ASH). Methods:, Male Sprague,Dawley rats were gavaged daily with alcohol (6 g/kg/d) or dextrose for 10 weeks ± l -NAME, l -NIL, or vehicle. Systemic and intestinal NO levels were measured by nitrites and nitrates in urine and tissue samples, oxidative damage to the intestinal mucosa by protein carbonyl and nitrotyrosine, intestinal permeability by urinary sugar tests, and liver injury by histological inflammation scores, liver fat, and myeloperoxidase activity. Results:, Alcohol caused tissue oxidation, gut leakiness, endotoxemia, and ASH. l -NIL and l -NAME, but not the d -enantiomers, attenuated all steps in the alcohol-induced cascade including NO overproduction, oxidative tissue damage, gut leakiness, endotoxemia, hepatic inflammation, and liver injury. Conclusions:, The mechanism we reported for alcohol-induced intestinal barrier disruption in vitro , NO overproduction, oxidative tissue damage, leaky gut, endotoxemia, and liver injury , appears to be relevant in vivo in an animal model of alcohol-induced liver injury. That iNOS inhibitors attenuated all steps of this cascade suggests that prevention of this cascade in alcoholics will protect the liver against the injurious effects of chronic alcohol and that iNOS may be a useful target for prevention of ALD. [source]

Acute Alcohol Intoxication During Hemorrhagic Shock: Impact on Host Defense From Infection

ALCOHOLISM, Issue 4 2004
K. L. Zambell
Abstract: Background: Acute alcohol intoxication is a frequent underlying condition associated with traumatic injury. Our studies have demonstrated that acute alcohol intoxication significantly impairs the immediate hemodynamic, metabolic, and inflammatory responses to hemorrhagic shock. This study investigated whether acute alcohol intoxication during hemorrhagic shock would alter the outcome from an infectious challenge during the initial 24 hr recovery period. Methods: Chronically catheterized male Sprague Dawley® rats were randomized to acute alcohol intoxication (EtOH; 1.75 g/kg bolus followed by a constant 15 hr infusion at 250,300 mg/kg/hr) or isocaloric isovolemic dextrose infusion (dex; 3 ml + 0.375 ml/hr). EtOH and dex were assigned to either fixed-volume (50%) hemorrhagic shock followed by fluid resuscitation with Ringer's lactate (EtOH/hem, dex/hem) or sham hemorrhagic shock (EtOH/sham, dex/sham). Indexes of circulating neutrophil function (apoptosis, phagocytosis, oxidative burst) were obtained at baseline, at completion of hemorrhagic shock, and at the end of fluid resuscitation. Bacterial clearance, lung cytokine expression, and myeloperoxidase activity were determined at 6 and 18 hr after an intratracheal challenge with Klebsiella pneumoniae (107 colony-forming units). Results: Mean arterial blood pressure was significantly lower in acute alcohol intoxication-hemorrhagic shock animals throughout the hemorrhagic shock. In sham animals, acute alcohol intoxication alone did not produce significant changes in neutrophil apoptosis or phagocytic activity but significantly suppressed phorbol myristic acid (PMA)-stimulated oxidative burst. Hemorrhagic shock produced a modest increase in neutrophil apoptosis and suppression of neutrophil phagocytic capacity but significantly suppressed PMA-stimulated oxidative burst. Acute alcohol intoxication exacerbated the hemorrhagic shock-induced neutrophil apoptosis and the hemorrhagic shock-induced suppression of phagocytosis without further affecting PMA-stimulated oxidative burst. Fluid resuscitation did not restore neutrophil phagocytosis or oxidative burst. Acute alcohol intoxication decreased (,40%) 3-day survival from K. pneumoniae in hemorrhagic shock animals, impaired bacterial clearance during the first 18 hr postinfection, and prolonged lung proinflammatory cytokine expression. Conclusions: These results demonstrate that the early alterations in metabolic and inflammatory responses to hemorrhagic shock produced by acute alcohol intoxication are associated with neutrophil dysfunction and impaired host response to a secondary infectious challenge leading to increased morbidity and mortality. [source]

The membrane attack complex (C5b-9) in liver cold ischemia and reperfusion injury

Constantino Fondevila
Activation of the complement cascade represents an important event during ischemia/reperfusion injury (IRI). This work was designed to investigate the role of the membrane attack complex (MAC; C5b-9) in the pathogenesis of hepatic IRI. Livers from B&W/Stahl/rC6(+) and C6(,) rats were harvested, stored for 24 hours at 4°C, and then transplanted [orthotopic liver transplantation (OLT)] to syngeneic recipients. There were 4 experimental groups: (1) C6(+),C6(+), (2) C6(+),C6(,), (3) C6(,),C6(+), and (4) C6(,),C6(,). At day +1, C6(,) OLTs showed decreased vascular congestion/necrosis, contrasting with extensive necrosis in C6(+) livers, that was independent of the recipient C6 status (Suzuki score: 7.2 ± 0.9, 7.3 ± 1.3, 4.5 ± 0.6, and 4.8 ± 0.4 for groups 1-4, respectively, P < 0.05). The liver function improved in recipients of C6(,) grafts (serum glutamic oxaloacetic transaminase: 2573 ± 488, 1808 ± 302, 1170 ± 111, and 1188 ± 184 in groups 1-4, respectively, P < 0.05). Intragraft macrophage infiltration (ED-1 immunostaining) and neutrophil infiltration (myeloperoxidase activity) were reduced in C6(,) grafts versus C6(+) grafts (P = 0.001); these data were confirmed by esterase staining (naphthol). The expression of proinflammatory interferon-,, interleukin-1,, and tumor necrosis factor messenger RNA/protein was also reduced in C6(,) OLTs in comparison with C6(+) OLTs. Western blot,assisted expression of proapoptotic caspase-3 was decreased in C6(,) OLTs versus C6(+) OLTs (P = 0.006), whereas antiapoptotic Bcl-2/Bag-1 was enhanced in C6(,) OLTs compared with C6(+) OLTs (P = 0.001). Terminal deoxynucleotidyl transferase,mediated dUTP nick end-labeling staining of apoptotic cells was enhanced (P < 0.05) in C6(+) OLTs compared with C6(,) OLTs. Thus, the terminal products of the complement system are essential in the mechanism of hepatic IRI. This is the first report using a clinically relevant liver cold ischemia model to show that local MAC inhibition attenuates IRI cascade in OLT recipients. Liver Transpl 14:1133,1141, 2008. © 2008 AASLD. [source]

Polaprezinc attenuates the Helicobacter pylori -induced gastric mucosal leucocyte activation in Mongolian gerbils,a study using intravital videomicroscopy

H. Suzuki
Background: We previously demonstrated that Helicobacter pylori colonization evokes gastric mucosal inflammation and an extensive increase in lipid peroxides and glutathione in Mongolian gerbils. Zinc and its derivative, polaprezinc, have been reported to be potent antioxidants in gastric mucosa. Aim: To examine the effect of polaprezinc on gastric mucosal oxidative inflammation in H. pylori -colonized Mongolian gerbils. Methods: Sixty-eight male Mongolian gerbils were orally inoculated with H. pylori (ATCC43504, 5 × 108 CFUs/gerbil; H. pylori group) and 35 gerbils were inoculated with the culture media (control group). Twenty-two gerbils in the H. pylori and 13 gerbils in the control group were fed with diets containing polaprezinc (0.06%, 100 mg/kg, 10 times the usual clinical dose) (H. pylori + polaprezinc group, polaprezinc group). The remaining gerbils were fed a standard laboratory chow diet. Neutrophil infiltration, assessed histologically and by the activity of myeloperoxidase, the contents of CXC-chemokine (GRO/CINC-1-like protein) and the contents of thiobarbituric acid-reactive substances, was evaluated in each group 12 weeks after the inoculation. Separately, gastric mucosal leucocyte activation and capillary perfusion were also assessed using intravital microscopy 2, 4, 8 and 12 weeks after the inoculation. Results: In all H. pylori -inoculated animals, the bacterial infection persisted throughout the experimental period. Gastric mucosal lesion formation in the H. pylori group was significantly inhibited in the H. pylori + polaprezinc group. Elevated levels of myeloperoxidase activity, GRO/CINC-1 and thiobarbituric acid-reactive substances in the H. pylori group at 12 weeks were attenuated significantly by polaprezinc treatment. Enhanced levels of venular leucocyte activation observed in the H. pylori group were attenuated significantly in the H. pylori + polaprezinc group during both the early phase (2 weeks) and late phase (12 weeks). Conclusion: Polaprezinc inhibited H. pylori -associated gastric mucosal oxidative inflammation, including initial micro-vascular leucocyte activation, in Mongolian gerbils. [source]

Brain Endothelial Adhesion Molecule Expression in Experimental Colitis

ABSTRACT Objectives: 1) To determine if endothelial expression of adhesion molecules involved in leukocyte recruitment is increased in the brain and other organs in four different models of experimental colitis, and 2) to investigate whether leukocyte infiltration occurs in the brain of colitic animals. Methods: Endothelial vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) expression was quantified, using the dual radiolabeled antibody technique in rats with trinitrobenzenesulfonic acid (TNBS)-induced colitis, in mice with dextran sulfate sodium (DSS)-induced colitis, in SCID mice reconstituted with CD45RBhigh T-cells, and in IL-10,/, mice. Leukocyte infiltration in the brain of TNBS-induced colitic rats was assessed by myeloperoxidase activity and immunohistochemical staining with anti-CD45 monoclonal antibody. Results: Marked upregulation of brain endothelial VCAM-1 (2- to 5.5-fold) was consistently found in colitic animals in the four models studied. Brain VCAM-1 strongly correlated with colon VCAM-1 and colon weight. By contrast, upregulation of brain ICAM-1 in colitic animals was only observed in the CD45RBhigh transfer (3-fold) and the TNBS-induced (1.5-fold models). Heart and muscle VCAM-1 and ICAM-1 were not upregulated in colitic animals in the majority of models studied. There was no leukocyte infiltration into the brain of TNBS-induced colitic rats. Conclusions: Our study demonstrates a marked and specific upregulation of endothelial VCAM-1 in the brain of colitic animals. This activation of cerebral endothelial cells was not associated with an infiltration of leukocytes into brain tissue. [source]

Endogenous and exogenous ghrelin enhance the colonic and gastric manifestations of dextran sodium sulphate-induced colitis in mice

B. De Smet
Abstract, Ghrelin is an important orexigenic peptide that not only exerts gastroprokinetic but also immunoregulatory effects. This study aimed to assess the role of endogenous and exogenous ghrelin in the pathogenesis of colitis and in the disturbances of gastric emptying and colonic contractility during this process. Dextran sodium sulphate colitis was induced for 5 days in (i) ghrelin+/+ and ghrelin,/, mice and clinical and histological parameters were monitored at days 5, 10 and 26 and (ii) in Naval Medical Research Institute non-inbred Swiss (NMRI) mice treated with ghrelin (100 nmol kg,1) twice daily for 5 or 10 days. Neural contractility changes were measured in colonic smooth muscle strips, whereas gastric emptying was measured with the 14C octanoic acid breath test. Inflammation increased ghrelin plasma levels. Body weight loss, histological damage, myeloperoxidase activity and IL-1, levels were attenuated in ghrelin,/, mice. Whereas absence of ghrelin did not affect changes in colonic contractility, gastric emptying in the acute phase was accelerated in ghrelin+/+ but not in ghrelin,/, mice. In agreement with the studies in ghrelin knockout mice, 10 days treatment of NMRI mice with exogenous ghrelin enhanced the clinical disease activity and promoted infiltration of neutrophils and colonic IL-1, levels. Unexpectedly, ghrelin treatment decreased excitatory and inhibitory neural responses in the colon of healthy but not of inflamed NMRI mice. Endogenous ghrelin enhances the course of the inflammatory process and is involved in the disturbances of gastric emptying associated with colitis. Treatment with exogenous ghrelin aggravates colitis, thereby limiting the potential therapeutic properties of ghrelin during intestinal inflammation. [source]

Neural mechanisms of early postinflammatory dysmotility in rat small intestine

I. Demedts
Abstract, Although human postinflammatory dysmotility is known, so far animal studies have primarily investigated changes during inflammation. Here, we focused on postinflammatory changes in rat jejunal myenteric plexus and jejunal motility. Evolution of ethanol/2,4,6-tri-nitrobenzene sulphonic acid (TNBS)-induced inflammation was assessed histologically and by measuring myeloperoxidase activity (MPO). Electromyography and immunohistochemistry were performed 1 week after ethanol/TNBS and also after NG -nitro- l -arginine methyl ester (l -NAME) administration. Ethanol/TNBS induced a transient inflammation, with normalization of MPO and histological signs of an early phase of recovery after 1 week. The number of cholinergic neurones was not altered, but myenteric neuronal nitric oxide synthase (nNOS)-immunoreactivity was significantly lower in the early phase of recovery after TNBS compared with water (1.8 ± 0.2 vs 3.5 ± 0.2 neurones ganglion,1, P < 0.001). Interdigestive motility was disrupted with a loss of phase 1 quiescence, an increase of migrating myoelectric complex cycle length, a higher number of non-propagated activity fronts and a decrease of adequately propagated phase 3 s after TNBS. Administration of l -NAME resulted in a similar disruption of interdigestive motility patterns. In the early phase of recovery after ethanol/TNBS-induced jejunal inflammation, a loss of motor inhibition occurs due to a decrease of myenteric nNOS activity. These observations may provide a model for early postinflammatory dysmotility syndromes. [source]

Effects of a herbal gel containing carvacrol and chalcones on alveolar bone resorption in rats on experimental periodontitis

Marco Antonio Botelho
Abstract Carvacrol and dimeric chalcones are the respective bioactive components of Lippia sidoides and Myracrodruon urundeuva, popular medicinal plants of Northeastern Brazil with proven antimicrobial and antiinflammatory properties. Periodontal disease is associated with inflammation and microbiological proliferation, thus the study aimed to investigate the effect of a topical gel based on carvacrol and chalcones in the experimental periodontal disease (EPD) in rats. Animals were treated with carvacrol and/or chalcones gel, immediately after EPD induction, three times a day for 11 days. Appropriate controls were included in the study. Animals were weighed daily. They were killed on day 11, the mandibles dissected and alveolar bone loss was measured. The periodontium were examined at histopathology and the neutrophil influx into the gingiva was assayed using myeloperoxidase activity. The bacterial flora were assessed through culture of the gingival tissue. Alveolar bone loss was significantly (p < 0.05) inhibited by combined carvacrol and chalcones gel, compared with the vehicle and non-treated groups. The treatment with the combined gel reduced tissue lesion at histopathology, decreased myeloperoxidase activity in gingival tissue and inhibited the growth of oral microorganisms as well as the weight loss. Carvacrol and chalcones combination gel has a beneficial effect upon EPD in this model. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Myeloperoxidase response to peritonitis in an experimental model

Veronica Yao
Introduction: Patients with peritonitis often exhibit systemic manifestations of sepsis, especially in the lungs. The aim of the present study was to evaluate the local and systemic effects of the neutrophil response to peritonitis in a rat model. Methods: Fifty Wistar rats were randomized to either a control group or a peritonitis group (5 mg zymosan intraperitoneal). Groups of five animals were killed at 4, 18, 24, 48 and 96 h for evaluation of the morphology of the peritoneum (mesothelial imprint), the number and phenotype of cells within peritoneal fluid (flow cytometry), and myeloperoxidase activity within the peritoneal fluid and distant organs (enzyme assay). Results: Zymosan produced macroscopic evidence of peritonitis and on microscopy there was disruption of peritoneal mesothelial cells. This was accompanied by an influx of neutrophils between 4 and 48 h (P < 0.001) and macrophages between 48 and 96 h (P < 0.001). There was also an increase in myeloperoxidase activity within peritoneal fluid between 4 and 48 h (P < 0.05), the lung at 4 h (P < 0.01) and the liver at 48 h (P < 0.001). Conclusion: The present study has confirmed the validity of using zymosan to create a low-morbidity model of peritonitis. Besides the anticipated peritoneal response, there were distant effects of neutrophil activation within the lungs and liver. In the future, strategies that modulate neutrophil activation within these organs might play a useful adjunctive role in the management of patients with peritonitis. [source]

Modulation of the innate immune response of rohu Labeo rohita (Hamilton) by experimental freshwater lice Argulus siamensis (Wilson) infection

Shailesh Saurabh
Abstract The study was undertaken to determine the modulation in innate immune response of rohu (Labeo rohita) during experimental freshwater lice Argulus siamensis infection. Results showed that serum ,-2 macroglobulin (,-2M) activity, ceruloplasmin level and alternative complement activity were significantly (P<0.05) lower in fish at different degrees of lice infection in comparison with uninfected control. No significant difference (P>0.05) in haemagglutination titre was observed in fish with low- and high-degree lice infections as compared with uninfected control. The serum lysozyme level was significantly (P<0.05) lower in low degree of lice infection as compared with control fish. The total serum antiprotease, myeloperoxidase activity and total protein level were not significantly different (P>0.05) in different degrees of lice-infected fish with respect to the control fish. The study indicated that A. siamensis infection modulated the immune system of rohu by suppressing the ,-2M, serum complement activities and ceruloplasmin level and through induction of stress response. The baseline data obtained in the present study have tremendous importance in understanding the susceptibility of rohu to different degrees of parasitosis and might be useful in controlling this dreaded ectoparasitic infection in fish. [source]

Attenuation of Bleomycin-Induced Lung Fibrosis by Oxymatrine Is Associated with Regulation of Fibroblast Proliferation and Collagen Production in Primary Culture

Xiaohong Chen
Oxymatrine is an alkaloid extracted from the Chinese herb Sophora japonica (Sophora flavescens Ait.) with capacities of anti-inflammation, inhibition of immune reaction, antivirus, protection against acute lung injury and antihepatic fibrosis. In this study, the effect of oxymatrine on pulmonary fibrosis was investigated using a bleomycin-induced pulmonary fibrosis mouse model. The results showed that bleomycin challenge provoked severe pulmonary fibrosis with marked increase in hydroxyproline content of lung tissue and lung fibrosis fraction, which was prevented by oxymatrine in a dose-dependent manner. In addition, bleomycin injection resulted in a marked increase of myeloperoxidase activity and malondialdehyde level that was attenuated by oxymatrine. Administration of oxymatrine inhibited the proliferation of murine lung fibroblasts, arrested the cells at G0/G1 phase and reduced the expression of cell cycle regulatory protein, cyclin D1 in vitro. Furthermore, the steady-state production of collagen and the expression of ,1(I) pro-collagen and ,2(I) pro-collagen mRNA in fibroblasts were inhibited by oxymatrine in a dose-dependent manner. These results suggested that oxymatrine may attenuate pulmonary fibrosis induced by bleomycin in mice, partly through inhibition of inflammatory response and lipid peroxidation in lung induced by bleomycin and reduction of fibroblast proliferation and collagen synthesis. [source]

The protective and healing effects of a natural antioxidant formulation based on ubiquinol and Aloe vera against dextran sulfate-induced ulcerative colitis in rats

BIOFACTORS, Issue 1-4 2003
Ludmila Korkina
Abstract Oxygen/nitrogen reactive species (ROS/RNS) are currently implicated in the pathogenesis of ulcerative colitis, drawing attention on the potential prophylactic and healing properties of antioxidants, scavengers, chelators. We evaluated the possible protective/curative effects of a natural antioxidant preparation based on Aloe vera and ubiquinol, against intestinal inflammation, lesions, and pathological alterations of the intestinal electrophysiological activity and motility, in a rat model of DSS-induced colitis. 5% dextrane sulfate (DDS) (3 days), followed by 1% DSS (4 days) was administered in drinking water. The antioxidant formulation (25 mg/kg) was delivered with a pre-treatment protocol, or simultaneously or post-colitis induction. Spontaneous and acetylcholine-stimulated electrical activity were impaired in the small intestine and in distal colon, upon exposure to DSS only. Severe inflammation occurred, with increased myeloperoxidase activity, and significant alterations of the oxidant/antioxidant status in colonic tissue and peritoneal cells. Lipoperoxidation, superoxide production, glutathione peroxidase and glutathione-S-transferase activities, and reduced glutathione content increased, whilst superoxide dismutase and catalase activities were sharply suppressed in colon tissue. ROS/RNS formation in peritoneal cells was strongly inhibited. Inflammation, electrical/mechanical impairment in the gut, and a great majority of oxidative stress parameters were improved substantially by pre-treatment with the antioxidant preparation, but not by simultaneous administration or post-treatment. [source]

Anti-inflammatory actions of aprotinin provide dose-dependent cardioprotection from reperfusion injury

J M Carter
Background and purpose: Myocardial injury following ischaemia and reperfusion has been attributed to activation and transmigration of polymorphonuclear leukocytes (PMNs) with release of mediators including oxygen-derived radicals and proteases causing damage. Experimental approach: We studied the serine protease inhibitor aprotinin in an in vivo rabbit model of 1 h of myocardial ischaemia followed by 3 h of reperfusion (MI+R). Aprotinin (10 000 Ukg,1) or its vehicle were injected 5 min prior to the start of reperfusion. Key results: Myocardial injury was significantly reduced with aprotinin treatment as indicated by a reduced necrotic area (11±2.7% necrosis as percentage of area at risk after aprotinin; 24±3.1% after vehicle; P<0.05) and plasma creatine kinase activity (12.2±1.5 and 17.3±2.3 IU g,1 protein in aprotinin and vehicle groups, respectively, P<0.05). PMN infiltration (assessed by myeloperoxidase activity) was significantly decreased in aprotinin-treated animals compared to vehicle (P<0.01). Histological analysis also revealed a substantial increase in PMN infiltration following MI+R and this was significantly reduced by aprotinin therapy (44±15 vs 102±2 PMN mm2 in aprotinin vs vehicle-treated animals, P<0.05). In parallel in vitro experiments, aprotinin inhibited neutrophil-endothelium interaction by reducing PMN adhesion on isolated, activated aortic endothelium. Finally, immunohistochemical analysis illustrated aprotinin significantly reduced myocardial apoptosis following MI+R. Conclusions and implications: Inhibition of serine proteases by aprotinin inhibits an inflammatory cascade initiated by MI+R. The cardioprotective effect appears to be at least partly due to reduced PMN adhesion and infiltration with subsequently reduced myocardial necrosis and apoptosis. British Journal of Pharmacology (2008) 155, 93,102; doi:10.1038/bjp.2008.223; published online 9 June 2008 [source]

Hypertonic saline attenuates end-organ damage in an experimental model of acute pancreatitis

C. J. Shields
Background Hypertonic saline (HTS) has been noted previously to reduce neutrophil activation. The aim of this study was to elucidate the effect of hypertonic resuscitation on the development of end-organ damage in an animal model of pancreatitis. Methods Pancreatitis was induced in Sprague,Dawley rats by intraperitoneal injection of 20 per cent l -arginine. Animals were randomized into four groups (each n = 8): controls; pancreatitis without intervention; pancreatitis plus intravenous resuscitation with normal saline (0·9 per cent sodium chloride 2 ml/kg) at 24 and 48 h; or HTS (7·5 per cent sodium chloride 2 ml/kg) at these time points. Pulmonary endothelial leakage was assessed by measurement of lung wet: dry ratios, bronchoalveolar lavage protein and myeloperoxidase activity. Results Animals that received HTS showed less pancreatic damage than those resuscitated with normal saline (1·0 versus 3·0; P = 0·04). Lung injury scores were also significantly diminished in the HTS group (1·0 versus 3·5; P = 0·03). Pulmonary neutrophil sequestration (myeloperoxidase activity 1·80 units/g) and increased endothelial permeability (bronchoalveolar lavage protein content 1287 ,g/ml) were evident in animals resuscitated with normal saline compared with HTS (1·22 units/g and 277 ,g/ml respectively; P < 0·02). Conclusion HTS resuscitation results in a significant attenuation of end-organ injury following a systemic inflammatory response to severe pancreatitis. © 2000 British Journal of Surgery Society Ltd [source]

Resuscitation with Na+/H+ exchanger inhibitor in traumatic haemorrhagic shock: Cardiopulmonary performance, oxygen transport and tissue inflammation

Dongmei Wu
Summary 1. The aim of the present study was to examine the effects of inhibition of the Na+/H+ exchanger (NHE-1) on cardiopulmonary performance, oxygen carrying capacity and tissue inflammation in a pig model of traumatic haemorrhage,resuscitation. 2. In 12 instrumented anaesthetized pigs, traumatic haemorrhage was modelled by producing tibia fractures, followed by haemorrhage of 25 mL/kg for 20 min, and then a 4 mm hepatic arterial tear with surgical repair after 20 min. Animals then underwent low-volume fluid resuscitation with either Hextend (vehicle; n = 6; Hospira, Lake Forest, IL, USA) or 3 mg/kg BIIB513 (an NHE-1 inhibitor) + Hextend (n = 6). The experiment was terminated 6 h after the beginning of resuscitation. 3. Compared with vehicle-treated controls, the addition of NHE-1 inhibition with BIIB513 significantly improved the left ventricle stroke work index and attenuated increases in pulmonary arterial pressure and pulmonary vascular resistance. Furthermore, BIIB513 treatment significantly increased the oxygenated haemoglobin ratio, blood oxygen content and mixed venous blood oxygen saturation and improved blood oxygen delivery. In addition, BIIB513 treatment reduced lung tissue levels of interleukin-6 by 80%, tumour necrosis factor-, by 37% and myeloperoxidase activity by 38%. Nuclear factor-,B DNA binding activity in the lung was also slightly and significantly attenuated following BIIB513 treatment. 4. In conclusion, the present study shows that NHE-1 inhibition facilitates the response to fluid resuscitation after traumatic haemorrhage by improving cardiac function, pulmonary vascular function and oxygen carrying capacity, which results in reduced tissue inflammatory injury. [source]

Bacterial translocation in a non-lethal rat model of peritonitis

V. Yao
Background Bacterial translocation from the gut may occur under a variety of different clinical circumstances and has been implicated in the development of multiple organ failure. The aim of this study was to determine the distribution of bacterial translocation occurring in a model of chemically induced peritonitis. We also sought to document the degree of the associated immune and inflammatory response. Methods Though a midline laparotomy, rats were injected with 5 mg of zymosan (in 0.2 ml of saline) into the subomental space. After 4, 18, 24, 48 and 96 h, a number of endpoints evaluated: intraperitoneal cellular influx, TNF-, and interleukin-6 concentrations and myeloperoxidase activity. Bacterial cultures were initiated from the free peritoneal fluid, mesenteric lymph nodes, liver, lung, and kidney. Imprints were also made of the peritoneal mesothelial surface to determine its integrity. Results When comparing rats injected with zymosan with the controls, there was evidence of a peritoneal inflammatory response within 4 hours. Facultative gram negative bacteria were found to be growing in the mesenteric lymph nodes and in the peritoneal fluid at 48 h. Anaerobic organisms were also cultured from the peritoneal fluid at 48 h. No organisms were cultured from the liver, lung or kidneys. In addition there was a significant increase in intraperitoneal cell numbers (predominantly neutrophils, P < 0.05), myeloperoxidase activity (P < 0.05) and TNF-, and IL-6 concentrations (P < 0.05). There was extensive loss of the peritoneal mesothelial cells. The peritoneal inflammatory changes and bacterial translocation had resolved by 96 h. Conclusion Bacterial translocation can be induced by the presence of an acute inflammatory focus in the peritoneal cavity. The translocation and inflammatory changes were associated with extensive loss of mesothelial cells. Nonetheless, these changes all resolved, indicating that the peritoneal cavity has a significant capacity to deal with such insults. A clearer understanding of the cellular and molecular events involved in the resolution phase could lead to improvements in the treatment of peritonotis. [source]