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Hepatic Lipid Peroxidation (hepatic + lipid_peroxidation)
Selected AbstractsThe effects of N-acetylcysteine on the expression of matrix metalloproteinase-2 and tissue inhibitor of matrix metalloproteinase-2 in hepatic fibrosis in bile duct ligated ratsHEPATOLOGY RESEARCH, Issue 12 2008Arezou Rezaei Aim:, N-acetylcysteine can inhibit the formation of intracellular reactive oxygen intermediates. Cellular redox state plays a role in regulating the secretion of matrix metalloproteinase-2. We investigated the effects of N-acetylcysteine on the expression of matrix metalloproteinase-2 and tissue inhibitor of matrix metalloproteinase-2. Methods:, Bile duct ligated rats were used as a model of hepatic fibrosis. We compared the level of gene expression (using real-time reverse transcription polymerase chain reaction [RT,PCR]), liver function parameters, hepatic reactive oxygen production, lipid peroxidation and glutathione state in experimental groups. Results:, N-acetylcysteine treatment significantly improved liver function parameters including the plasma levels of aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase and bilirubin. In addition, significant improvement of glutathione state and reactive oxygen production were observed. Hepatic lipid peroxidation was reversed by N-acetylcysteine treatment. Although N-acetylcysteine treatment did not completely normalize the increased matrix metalloproteinase-2 expression, it significantly decreased its level by 65%. N-acetylcysteine treatment also significantly decreased matrix metalloproteinase-2 activity and normalized tissue inhibitor of matrix metalloproteinase-2 expression. Conclusion:, Collectively, N-acetylcysteine showed inhibition of matrix metalloproteinase-2 expression and activity. In addition, administration of N-acetylcysteine was associated with downregulation of the expression of tissue inhibitor of matrix metalloproteinase-2 and amelioration of oxidative stress in the liver of bile duct ligated rats. [source] Amelioration of oxidative stress by dandelion extract through CYP2E1 suppression against acute liver injury induced by carbon tetrachloride in sprague-dawley ratsPHYTOTHERAPY RESEARCH, Issue 9 2010Chung Mu Park Abstract The protective effects of common dandelion leaf water extract (DLWE) were investigated by carbon tetrachloride (CCl4) induced hepatitis in Sprague-Dawley rats. The animals were divided into five groups: normal control, DLWE control, CCl4 control, and two DLWE groups (0.5 and 2,g/kg bw). After 1 week of administering corresponding vehicle or DLWE, a single dose of CCl4 (50% CCl4/olive oil; 0.5,mL/kg bw) was administered 24,h before killing in order to produce acute liver injury. The DLWE treatment significantly decreased CCl4 -induced hepatic enzyme activities (AST, ALT and LDH) in a dose dependent manner. Also, the obstructed release of TG and cholesterol into the serum was repaired by DLWE administration. Hepatic lipid peroxidation was elevated while the GSH content and antioxidative enzyme activities were reduced in the liver as a result of CCl4 administration, which were counteracted by DLWE administration. Furthermore, the hepatocytotoxic effects of CCl4 were confirmed by significantly elevated Fas and TNF-? mRNA expression levels, but DLWE down-regulated these expressions to the levels of the normal control. Highly up-regulated cytochrome P450 2E1 was also lowered significantly in the DLWE groups. These results indicate that DLWE has a protective effect against CCl4 -induced hepatic damage with at least part of its effect being attributable to the attenuation of oxidative stress and inflammatory processes resulting from cytochrome P450 activation by CCl4. Copyright © 2010 John Wiley & Sons, Ltd. [source] The influence of curcumin and manganese complex of curcumin on cadmium-induced oxidative damage and trace elements status in tissues of miceJOURNAL OF APPLIED TOXICOLOGY, Issue 3 2006Vladislav Eybl Abstract Curcumin (diferuoyl methane) from turmeric is a well-known biologically active compound. It has been shown to ameliorate oxidative stress and it is considered to be a potent cancer chemopreventive agent. In our previous study the antioxidative effects of curcumin in cadmium exposed animals were demonstrated. Also manganese exerts protective effects in experimental cadmium intoxication. The present study examined the ability of the manganese complex of curcumin (Mn-curcumin) and curcumin to protect against oxidative damage and changes in trace element status in cadmium-intoxicated male mice. Curcumin or Mn-curcumin were administered at equimolar doses (0.14 mmol/kg b.w.) for 3 days, by gastric gavages, dispersed in methylcellulose. One hour after the last dose of antioxidants, cadmium chloride (33 µmol/kg) was administered subcutaneously. Both curcumin and Mn-curcumin prevented the increase of hepatic lipid peroxidation , expressed as MDA level, induced by cadmium intoxication and attenuated the Cd-induced decrease of hepatic GSH level. No change in hepatic glutathione peroxidase or catalase activities was found in Cd-exposed mice. A decreased GSH-Px activity was measured in curcumin and Mn-curcumin alone treated mice. Neither curcumin nor Mn-curcumin treatment influenced cadmium distribution in the tissues and did not correct the changes in the balance of essential elements caused by Cd-treatment. The treatment with Mn-curcumin increased the Fe and Mn content in the kidneys of both control and Cd-treated mice and Fe and Cu content in the brain of control mice. In conclusion, regarding the antioxidative action, introducing manganese into the curcumin molecule does not potentiate the studied effects of curcumin. Copyright © 2005 John Wiley & Sons, Ltd. [source] Galactosamine-induced hepatotoxic effect and hepatoprotective role of a protein isolated from the herb Cajanus indicus L in vivo,JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 1 2007Prasenjit Manna Abstract dd(+)-Galactosamine is a well-known experimental hepatotoxin. The present study was conducted to determine the protective role of a 43-kD protein isolated from the leaves of the herb Cajanus indicus L against dd(+)-galactosamine (GalN) induced liver damage in mice. Both preventive and curative effects of the protein have been investigated in the study. The protein was administered intraperitoneally at a dose of 2 mg/kg body weight for 4 days before and after GalN intoxication at a dose of 800 mg/kg body weight for 3 days. The increased activities of serum marker enzymes, alanine aminotransferase, and alkaline phosphatase because of GalN administration, were significantly reduced by the protein treatment. The protein also normalized the altered activities of antioxidant enzymes superoxide dismutase, catalase, glutathione reductase, and glutathione- S -transferase as well as the levels of cellular metabolites, reduced glutathione, glutathione disulfide, and total thiols. In addition, the enhanced hepatic lipid peroxidation because of GalN intoxication was also effectively inhibited by the protein treatment. Results suggest that GalN caused hepatic damages via oxidative insult and that the protein provided protection through its antioxidant mechanism. © 2007 Wiley Periodicals, Inc. J Biochem Mol Toxicol 21:13,23, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20154 [source] Effects of benzo[a]pyrene on tissue activities of metabolizing enzymes and antioxidant system in normal and protein-malnourished ratsJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 2 2003Osama A. Badary Abstract The effects of benzo[a]pyrene (B[a]P) on some drug-metabolizing and antioxidant systems in liver, lung, and stomach were investigated in normal and protein malnutrition (PM) rats. PM significantly inhibited tissue glutathione (GSH) content and increased hepatic lipid peroxidation. Cytochrome P450 isoform CYP1A1 was significantly increased in various tissues (42,73%). Also, lung glutathione S-transferase (GST) activity was significantly decreased (19%) in PM rats. On the other hand, B[a]P significantly induced tissue GSH of control and PM rats. Also, hepatic lipid peroxidation were significantly increased in control rats treated with B[a]P. Superoxide dismutase (SOD) activity was decreased by B[a]P treatment in PM rat stomach. B[a]P significantly induced both quinone reductase (QR) (in all tissues) and hepatic GST of control and PM rats. GST activity in PM rat liver was significantly higher than that of control rat liver after B[a]P treatment. Also, B[a]P induced hepatic CYP1A1 by 32-fold and 27-fold (P , 0.05) in control and PM rats, respectively. Stomach and hepatic UDP-glucuronosyltransferase activities were significantly decreased (34%) and increased (74%), respectively by B[a]P in PM rats. The results suggest that PM status has a modifying effect on the response of some antioxidant and metabolizing systems to a well-known carcinogen risk. © 2003 Wiley Periodicals, Inc. J Biochem Mol Toxicol 17:86,91, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10064 [source] Effects of quercetin on antioxidant defense in streptozotocin-induced diabetic ratsJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 3 2001Ruth A. Sanders Abstract In light of evidence that some complications of diabetes mellitus may be caused or exacerbated by oxidative damage, we investigated the effects of subacute treatment with the antioxidant quercetin on tissue antioxidant defense systems in streptozotocin-induced diabetic Sprague-Dawley rats (30 days after streptozotocin induction). Quercetin, 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-1-benzopyran-4-one, was administered at a dose of 10mg/kg/day, ip for 14 days, after which liver, kidney, brain, and heart were assayed for degree of lipid peroxidation, reduced and oxidized glutathione content, and activities of the free-radical detoxifying enzymes catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase. Treatment of normal rats with quercetin increased serum AST and increased hepatic concentration of oxidized glutathione. All tissues from diabetic animals exhibited disturbances in antioxidant defense when compared with normal controls. Quercetin treatment of diabetic rats reversed only the diabetic effects on brain oxidized glutathione concentration and on hepatic glutathione peroxidase activity. By contrast, a 20% increase in hepatic lipid peroxidation, a 40% decline in hepatic glutathione concentration, an increase in renal (23%) and cardiac (40%) glutathione peroxidase activities, and a 65% increase in cardiac catalase activity reflect intensified diabetic effects after treatment with quercetin. These results call into question the ability of therapy with the antioxidant quercetin to reverse diabetic oxidative stress in an overall sense. © 2001 John Wiley & Sons, Inc. J Biochem Mol Toxicol 15:143,149, 2001 [source] The pharmacological potential of Sorbus commixta cortex on blood alcohol concentration and hepatic lipid peroxidation in acute alcohol-treated ratsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2006Syng-Ook Lee The effect of Sorbus commixta cortex, a traditional herbal medicine used for the treatment of bronchitis, gastritis and dropsy, on blood alcohol concentration (BAC) and hepatic lipid peroxidation was examined in acute alcohol-treated rats. A 30-min pretreatment with a methanol extract of S. commixta cortex (SC) at concentrations higher than 200 mg kg,1 resulted in a significant decrease in BAC and the ethyl acetate fraction (SE) of the extract showed the highest potency, with a maximum of a 46% decrease at 150 mg kg,1 2h after alcohol administration (3.0 g kg,1) compared with the control group (P < 0.005). The rapid reduction in BAC did not appear to be due to the protection or activation of hepatic alcohol dehydrogenase (ADH) activity by SE. Hepatic malondialdehyde (MDA) levels were significantly increased by acute alcohol administration within 6h, although pretreatment with the SE caused a significant decrease in MDA levels compared with alcohol treatment alone. Hepatic glutathione (GSH) levels and superoxide dismutase (SOD) activity remained unchanged by alcohol, SE alone or by the combined treatment of alcohol and SE. However, catalase activity was significantly reduced by acute alcohol administration and pretreatment with the SE led to significant protection of its activity. These results suggest that pretreatment with SE reduces hepatic lipid peroxidation by decreasing the bioavailability of alcohol and its oxidative metabolites, such as H2O2, at least partly, through the protection of hepatic catalase in acute alcohol-treated rats. [source] Mechanisms of protection by melatonin against acetaminophen-induced liver injury in miceJOURNAL OF PINEAL RESEARCH, Issue 3 2006Tatsuya 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] Immunohistochemical Characterization of Hepatic Malondialdehyde and 4-Hydroxynonenal Modified Proteins During Early Stages of Ethanol-Induced Liver InjuryALCOHOLISM, Issue 6 2003Brante P. Sampey Background: Chronic ethanol consumption is associated with hepatic lipid peroxidation and the deposition or retention of aldehyde-adducted proteins postulated to be involved in alcohol-induced liver injury. The purpose of this study was to characterize hepatocellular formation of aldehyde-protein adducts during early stages of alcohol-induced liver injury. Methods: Female Sprague Dawley® rats were subjected to the intragastric administration of a low-carbohydrate/high-fat total enteral nutrition diet or a total enteral nutrition diet containing ethanol for a period of 36 days. Indexes of hepatic responses to ethanol were evaluated in terms of changes in plasma alanine aminotransferase activity, hepatic histopathologic analysis, and induction of cytochrome P-4502E1 (CYP2E1). Immunohistochemical methods were used to detect hepatic proteins modified with malondialdehyde (MDA) or 4-hydroxynonenal (4-HNE) for subsequent quantitative image analysis. Results: After 36 days of treatment, rats receiving the alcohol-containing diet displayed hepatic histopathologies characterized by marked micro- and macrosteatosis associated with only minor inflammation and necrosis. Alcohol administration resulted in a 3-fold elevation of plasma alanine aminotransferase activity and 3-fold increases (p < 0.01) in hepatic CYP2E1 apoprotein and activity. Quantitative immunohistochemical analysis revealed significant (p < 0.01) 5-fold increases in MDA- and 4-HNE modified proteins in liver sections prepared from rats treated with alcohol. The MDA- or 4-HNE modified proteins were contained in hepatocytes displaying intact morphology and were colocalized primarily with microvesicular deposits of lipid. Aldehyde-modified proteins were not prevalent in parenchymal or nonparenchymal cells associated with foci of necrosis or inflammation. Conclusions: These results suggest that alcohol-induced lipid peroxidation is an early event during alcohol-mediated liver injury and may be a sensitizing event resulting in the production of bioactive aldehydes that have the potential to initiate or propagate ensuing proinflammatory or profibrogenic cellular events. [source] Carbon Monoxide has Antioxidative Properties in the Liver Involving p38 MAP Kinase Pathway in a Murine Model of Systemic InflammationMICROCIRCULATION, Issue 7 2010JÜRGEN BRUGGER Please cite this paper as: Brugger, Schick, Brock, Baumann, Muellenbach, Roewer and Wunder (2010). Carbon Monoxide has Antioxidative Properties in the Liver Involving p38 MAP Kinase Pathway in a Murine Model of Systemic Inflammation. Microcirculation17(7), 504,513. Abstract Objective:, Reactive oxygen species (ROS) are important in the hepatocellular injury process during a systemic inflammation. We examined the role of carbon monoxide (CO) on the hepatic generation of ROS with in-vivo and in-vitro models of systemic inflammation. Methods:, Using a murine model of bilateral hindlimb ischemia-reperfusion (I/R) we examined the effect of CO treatment on hepatic ROS formation, oxidative status, and cell injury. Cultured HUVEC were used to investigate intracellular pathways. Results:, CO treatment reduced hepatic lipid peroxidation, re-established total hepatic glutathione and glutathione disulfide (GSH/GSSG) levels and reduced hepatocellular injury. Inhibition of heme oxygenase (HO) during treatment with CO during hindlimb I/R failed to alter the antioxidant qualities provided by CO. The production of ROS after tumor necrosis factor-, (TNF-,) stimulation in HUVEC was diminished after exposure to CO. Treatment with CO during HO inhibition reduced both ROS formation and cell injury. Inhibiting the p38 MAPK (mitogen-activated protein kinase) pathway with pyridinyl imidazol (SB203580) revealed that the antioxidant potential of CO involved the activation of p38 MAPK. Conclusions:, CO has direct antioxidant potential independently of any HO activity during systemic inflammation. The antioxidant effects afforded by CO involve the activation of the p38 MAPK pathway. [source] Hypocholesterolaemic and antioxidant effects of Glycyrrhiza glabra (Linn) in ratsMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 11 2006Nishant P. Visavadiya Abstract The hypocholesterolaemic and antioxidant effects of Glycyrrhiza glabra (GG) root powder were examined in hypercholesterolaemic male albino rats. A 4-week administration of GG root powder (5 and 10 gm% in diet) to hypercholesterolaemic rats resulted in significant reduction in plasma, hepatic total lipids, cholesterol, triglycerides and plasma low-density lipoprotein and VLDL-cholesterol accompanied by significant increases in HDL-cholesterol levels. Furthermore, significant increases in fecal cholesterol, neutral sterols and bile acid excretion along with an increase in hepatic HMG-CoA reductase activity and bile acid production were observed in these animals. The root powder administration to hypercholesterolaemic rats also decreased hepatic lipid peroxidation with a concomitant increase in superoxide dismutase (SOD) and catalase activities and total ascorbic acid content. Thus, the hypocholesterolaemic and antioxidant effects of GG root appeared to be mediated via (i) accelerated cholesterol, neutral sterol and bile acid elimination through fecal matter with an increased hepatic bile acid production and (ii) improving the activities of hepatic SOD, catalase and increasing the ascorbic acid content. The normo-cholesterolaemic animals when fed with GG root powder at 10 gm% level, registered a significant decline in plasma lipid profiles and an increase in HDL-cholesterol content. The antioxidant status of these animals also was improved upon treatment. [source] The effect of Anethum graveolens L. (dill) on corticosteroid induced diabetes mellitus: involvement of thyroid hormonesPHYTOTHERAPY RESEARCH, Issue 12 2008Sunanda Panda Abstract An investigation was made to evaluate the role of Anethum graveolens L. (dill) leaf extract in the regulation of corticosteroid-induced type 2 diabetes mellitus in female rats. In dexamethasone-treated animals (1 mg/kg for 22 days) an increase in serum concentration of insulin and glucose and in hepatic lipid peroxidation (LPO) was observed. However, there was a decrease in serum concentration of thyroid hormones and in the endogenous antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) in liver. In animals treated with an equivalent amount of dexamethasone for a similar period (22 days) when received the leaf extract (100 mg/kg b.wt/d.) for last 15 days a decrease in the concentration of both serum glucose and insulin was observed, indicating the potential of the plant extract in the regulation of corticosteroid-induced diabetes. Dexamethasone-induced alterations in the levels of thyroid hormones as well as in hepatic LPO, SOD, CAT and GSH were also reversed by the plant extract. Copyright © 2008 John Wiley & Sons, Ltd. [source] Evaluation of the antithyroid, antioxidative and antihyperglycemic activity of scopoletin from Aegle marmelos leaves in hyperthyroid ratsPHYTOTHERAPY RESEARCH, Issue 12 2006Sunanda Panda Abstract Scopoletin (7-hydroxy-6-methoxy coumarin) was isolated from the leaves of Aegle marmelos and evaluated for its potential to regulate hyperthyroidism, lipid peroxidation and hyperglycemia in levo-thyroxine-induced hyperthyroid rats. Scopoletin (1.00 mg/kg, p.o.) administered daily for 7 days to levo-thyroxine-treated animals decreased the levels of serum thyroid hormones and glucose as well as hepatic glucose-6-phosphatase activity, demonstrating its potential to regulate hyperthyroidism and hyperglycemia. Scopoletin also inhibited hepatic lipid peroxidation and increased the activity of antioxidants, superoxide dismutase and catalase. Compared with the standard antithyroid drug, propylthiouracil, scopoletin exhibited a superior therapeutic activity, since unlike propylthiouracil, it also inhibited hepatic lipid peroxidation. These findings indicate that scopoletin has the potential to inhibit thyroid function and hyperglycemia without hepatotoxicity. Copyright © 2006 John Wiley & Sons, Ltd. [source] Protective effect of binaphthyl diselenide, a synthetic organoselenium compound, on 2-nitropropane-induced hepatotoxicity in ratsCELL BIOCHEMISTRY AND FUNCTION, Issue 4 2010Mohammad Ibrahim Abstract Organoselenides have been documented as promising pharmacological agents against a number of diseases associated with oxidative stress. Here we have investigated, for the first time, the potential antioxidant activity of binaphthyl diselenide ((NapSe)2; 50,mg,kg,1, p.o.) against the 2-nitropropane (2-NP)-induced hepatoxicity in rats, using different end points of toxicity (liver histopathology, plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatinine). In addition, in view of the association of oxidative stress with 2-NP exposure, hepatic lipid peroxidation, ascorbic acid levels, ,-aminolevulinate dehydratase (,-ALA-D) and catalase (CAT) activities were evaluated. 2-NP caused an increase of AST, ALT and hepatic lipid peroxidation. 2-NP also caused hepatic histopathological alterations and ,-ALA-D inhibition. (NapSe)2 (50,mg,kg,1) prevented 2-NP-induced changes in plasmatic ALT and AST activities and also prevented changes in hepatic histology, ,-ALA-D and lipid peroxidation. Results presented here indicate that the protective mechanism of (NapSe)2 against 2-NP hepatotoxicity is possibly linked to its antioxidant activity. Copyright © 2010 John Wiley & Sons, Ltd. [source] Effect of selenium on N-nitrosodiethylamine-induced multistage hepatocarcinogenesis with reference to lipid peroxidation and enzymic antioxidantsCELL BIOCHEMISTRY AND FUNCTION, Issue 1 2001C. Thirunavukkarasu Abstract We have studied the relationship between antioxidant and anticancer properties of selenium (Se) in multistage hepatocarcinogenesis induced by N-nitrosodiethylamine (DEN). In this study we have observed an increased level of lipid peroxide (LPO) products and decreased antioxidant enzyme activities (superoxide dismutase and catalase) in hepatoma and surrounding liver tissues of cancer-bearing animals. Selenium (Se) was supplemented either before initiation or during initiation and selection/promotion phases of hepatocarcinogenesis and was found to be effective in altering hepatic lipid peroxidation and antioxidant enzyme activities to a statistically significant level measured either in the hepatoma or in the surrounding liver tissues. These alterations inclined towards normal in a time-dependent manner on selenium supplementation. Furthermore, increased levels of lipid peroxidation and decreased levels of antioxidants (superoxide dismutase and catalase) were also observed in distant organs of cancer-bearing rats other than the tumour-bearing site. These alterations are brought back to normal levels upon Se treatment. Our results confirm the fact that Se is particularly protective in limiting the action of DEN by its antioxidant property. Copyright © 2001 John Wiley & Sons, Ltd. [source] | ||||||||||||||||