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Acute Liver Injury (acute + liver_injury)
Kinds of Acute Liver Injury Selected AbstractsProtective effects of N-acetyl- L -cysteine against acute carbon tetrachloride hepatotoxicity in ratsCELL BIOCHEMISTRY AND FUNCTION, Issue 1 2008Yu. Z. Maksimchik Abstract In recent years, N-acetyl- L -cysteine (NAC) has been widely investigated as a potentially useful protective and antioxidative agent to be applied in many pathological states. The aim of the present work was further evaluation of the mechanisms of the NAC protective effect under carbon tetrachloride-induced acute liver injuries in rats. The rat treatment with CCl4 (4,g/kg, intragastrically) caused pronounced hepatolysis observed as an increase in blood plasma bilirubin levels and hepatic enzyme activities, which agreed with numerous previous observations. The rat intoxication was accompanied by an enhancement of membrane lipid peroxidation (1.4-fold) and protein oxidative damage (protein carbonyl group and mixed protein-glutathione disulphide formations) in the rat liver. The levels of nitric oxide in blood plasma and liver tissue significantly increased (5.3- and 1.5-fold, respectively) as blood plasma triacylglycerols decreased (1.6-fold). The NAC administration to control and intoxicated animals (three times at doses of 150,mg/kg) elevated low-molecular-weight thiols in the liver. The NAC administration under CCl4 -induced intoxication prevented oxidative damage of liver cells, decreased membrane lipid peroxidation, protein carbonyls and mixed protein-glutathione disulphides formation, and partially normalized plasma triacylglycerols. At the same time the NAC treatment of intoxicated animals did not produce a marked decrease of the elevated levels of blood plasma ALT and AST activities and bilirubin. The in vitro exposure of human red blood cells to NAC increased the cellular low-molecular-weight thiol levels and retarded tert -butylhydroperoxide-induced cellular thiol depletion and membrane lipid peroxidation as well as effectively inhibited hypochlorous acid-induced erythrocyte lysis. Thus, NAC can replenish non-protein cellular thiols and protect membrane lipids and proteins due to its direct radical-scavenging properties, but it did not attenuate hepatotoxicity in the acute rat CCl4 -intoxication model. Copyright © 2007 John Wiley & Sons, Ltd. [source] Constitutive androstane receptor (CAR) ligand, TCPOBOP, attenuates Fas-induced murine liver injury by altering Bcl-2 proteins,HEPATOLOGY, Issue 1 2006Edwina S. Baskin-Bey The constitutive androstane receptor (CAR) modulates xeno- and endobiotic hepatotoxicity by regulating detoxification pathways. Whether activation of CAR may also protect against liver injury by directly blocking apoptosis is unknown. To address this question, CAR wild-type (CAR+/+) and CAR knockout (CAR,/,) mice were treated with the CAR agonist 1,4-bis[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP) and then with the Fas agonist Jo2 or with concanavalin A (ConA). Following the administration of Jo2, hepatocyte apoptosis, liver injury, and animal fatalities were abated in TCPOBOP-treated CAR+/+ but not in CAR,/, mice. Likewise, acute and chronic ConA-mediated liver injury and fibrosis were also reduced in wild-type versus CAR,/, TCPOBOP-treated mice. The proapoptotic proteins Bak (Bcl-2 antagonistic killer) and Bax (Bcl-2-associated X protein) were depleted in livers from TCPOBOP-treated CAR+/+ mice. In contrast, mRNA expression of the antiapoptotic effector myeloid cell leukemia factor-1 (Mcl-1) was increased fourfold. Mcl-1 promoter activity was increased by transfection with CAR and administration of TCPOBOP in hepatoma cells, consistent with a direct CAR effect on Mcl-1 transcription. Indeed, site-directed mutagenesis of a putative CAR consensus binding sequence on the Mcl-1 promoter decreased Mcl-1 promoter activity. Mcl-1 transgenic animals demonstrated little to no acute liver injury after administration of Jo2, signifying Mcl-1 cytoprotection. In conclusion, these observations support a prominent role for CAR cytoprotection against Fas-mediated hepatocyte injury via a mechanism involving upregulation of Mcl-1 and, likely, downregulation of Bax and Bak. (HEPATOLOGY 2006;44:252,262.) [source] Neutrophil depletion protects against murine acetaminophen hepatotoxicity,,HEPATOLOGY, Issue 6 2006Zhang-Xu Liu We previously reported that liver natural killer (NK) and NKT cells play a critical role in mouse model of acetaminophen (APAP)-induced liver injury by producing interferon gamma (IFN-,) and modulating chemokine production and subsequent recruitment of neutrophils into the liver. In this report, we examined the role of neutrophils in the progression of APAP hepatotoxicity. C57BL/6 mice were given an intraperitoneal toxic dose of APAP (500 mg/kg), which caused severe acute liver injury characterized by significant elevation of serum ALT, centrilobular hepatic necrosis, and increased hepatic inflammatory cell accumulation. Flow cytometric analysis of isolated hepatic leukocytes demonstrated that the major fraction of increased hepatic leukocytes at 6 and 24 hours after APAP was neutrophils (Mac-1+Gr-1+). Depletion of neutrophils by in vivo treatment with anti-Gr-1 antibody (RB6-8C5) significantly protected mice against APAP-induced liver injury, as evidenced by markedly reduced serum ALT levels, centrilobular hepatic necrosis, and improved mouse survival. The protection was associated with decreased FasL-expressing cells, cytotoxicity against hepatocytes, and respiratory burst in hepatic leukocytes. In intracellular adhesion molecule (ICAM)-1,deficient mice, APAP caused markedly reduced liver injury when compared with wild-type mice. The marked protection in ICAM-1,deficient mice was associated with decreased accumulation of neutrophils in the liver. Hepatic GSH depletion and APAP-adducts showed no differences among the antibody-treated, ICAM-1,deficient, and normal mice. In conclusion, accumulated neutrophils in the liver contribute to the progression and severity of APAP-induced liver injury. (HEPATOLOGY 2006;43:1220,1230.) [source] Roles of AKT and sphingosine kinase in the antiapoptotic effects of bile duct ligation in mouse liver,HEPATOLOGY, Issue 6 2005Yosuke Osawa Tumor necrosis factor (TNF) receptor, and Fas-mediated apoptosis are major death processes of hepatocytes in liver disease. Although antiapoptotic effects in the injured liver promote chronic hepatitis and carcinogenesis, scant information is known about these mechanisms. To explore this issue, we compared acute liver injury after TNF-, or anti-Fas antibody (Jo2) between livers from sham-operated mice and chronic injured liver via bile duct ligation (BDL). BDL inhibited hepatocyte apoptosis induced by TNF-, but not by Jo2. On the other hand, BDL inhibited the massive hemorrhage seen in livers treated with either TNF-, or Jo2. Inactivation of AKT blocked the antiapoptotic effect of BDL. Sphingosine kinase knockout mice also lost the antihemorrhagic effect of BDL and attenuated the antiapoptotic effects of BDL. In bile duct,ligated livers, hepatic stellate cells (HSCs) were activated and produced tissue inhibitor of metalloproteinase 1 in a sphingosine kinase (SphK)-1,dependent mechanism. In conclusion, BDL exerts antiapoptotic effects that appear to require activation of AKT in hepatocytes and SphK in HSCs.(HEPATOLOGY 2005;42:1320,1328.) [source] Differential regulation of TGF-, signal in hepatic stellate cells between acute and chronic rat liver injuryHEPATOLOGY, Issue 1 2002Yoshiya Tahashi During chronic liver injury, transforming growth factor , (TGF-,) plays a prominent role in stimulating liver fibrogenesis by myofibroblast-like cells derived from hepatic stellate cells (HSCs). On the other hand, Smad 7 was recently shown to antagonize the TGF-,,induced activation of signal-transducing Smads (2 and 3). In this study, we investigated the regulatory mechanisms of the TGF-, signals in rat HSCs during acute liver injury and myofibroblasts (MFBs) during chronic liver injury, focusing on the roles of Smad 2 and antagonistic Smad 7. In acute liver injury, HSC-derived TGF-, increased plasminogen activator inhibitor type 1 (PAI-1) and ,2(I) procollagen (COL1A2) transcripts. Smad 2 in HSCs during liver injury and primary cultured HSCs were activated by an autocrine mechanism, because high levels of Smad 2 phosphorylation and induction of PAI-1 transcript by TGF-, were observed in HSCs. Thereafter, Smad 7 induced by TGF-, negatively regulated the Smad 2 action. These results indicated that endogenous TGF,,mediated Smad 7 in HSCs terminated the fibrotic signals mediated by signal-transducing Smads, and might be involved in the transient response to autocrine TGF-, signal after acute liver injury. By contrast, Smad 7 was not induced by the autocrine TGF-, signal, and constitutive Smad 2 activation was observed in MFBs throughout chronic liver injury, although Smad 7 could inhibit the TGF-, signal requiring Smad 2 phosphorylation by activated TGF-, receptor in cultured MFBs. This constitutive phosphorylation of Smad 2 by endogenous TGF-, under a low level of Smad 7 could be involved in the progression of liver fibrosis. [source] Differential expression of the genes involved in amino acids and nitrogen metabolisms during liver regeneration of miceHEPATOLOGY RESEARCH, Issue 3 2009Yunsheng Yuan Aim:, Liver regeneration is a highly coordinated response to hepatic injury or resection that is controlled by the body's overall requirement for liver function. The level of circulating amino acids in blood increases after acute liver injury and administration of amino acid mixtures induces hepatic DNA replication. These findings suggest a close connection between amino acid metabolism and hepatic proliferation. However, the underlying molecular mechanisms have not been completely elucidated. Here, we applied a cDNA micro-array technique to analyze expression profiles of the genes associated with nitrogen and amino acid metabolism during liver regeneration in mice following treatment with CCl4. Methods:, Seventy-nine genes were identified for their significantly altered expression patterns at different stages of liver damage and regeneration. Results:, We observed that the numbers of down-regulated genes were remarkably higher than that of up-regulated genes at 1.5 days following carbon tetrachloride administration when hepatic DNA replication was most active, indicating the existence of a counter balance between cell proliferation and liver metabolism functions. Conclusions:, Our results suggest that suppression of amino acids metabolism after acute liver injury results in the accumulation of amino acids in plasma that serves as a driving force for liver regeneration. [source] Protective effect of non-mitogenic human acidic fibroblast growth factor on hepatocyte injuryHEPATOLOGY RESEARCH, Issue 10 2007Hua Xu Aim:, To study whether non-mitogenic human acidic fibroblast growth factor (nm-haFGF) has protective effects on H2O2 -induced hepatocyte injury in vitro and CCl4 -induced hepatocyte injury in vivo. Methods:, (i) HL-7702 hepatocytes were incubated with different concentrations of nm-haFGF for 12 h, and then the activity of lactate dehydrogenase (LDH) in culture medium was detected, and genomic DNA electrophoresis analysis was observed after being exposed to H2O2 (8 mmol/L) for 4 h. Proximately, apoptotic rates and protein expressions of Bcl-2 and Bax of HL-7702 cell were detected after being exposed to H2O2 (0.2 mmol/L) for 20 h. (ii) Being injected intraperitoneally with nm-haFGF, mice were treated with CCl4 intraperitoneally to induce hepatic injury. Twenty-four hours later, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured and histopathologic changes were evaluated. Results:, (i) In vitro tests: LDH activities and apoptotic rates decreased, the protein expression of Bcl-2 increased and Baxdecreased in nm-haFGF-treated groups at the concentrations of 100 150 and 200 ng/mL, compared with that in the model control group, which was treated with H2O2 alone. The genomic DNA remained nearly intact at the concentrations of 150 and 200 ng/mL. (ii) In vivo tests: serum ALT and AST in nm-haFGF-treated groups (10 ,g/kg and 20 ,g/kg) were much lower as compared to the model control group, which was treated with CCl4 alone. Histological examination showed that nm-haFGF markedly ameliorated hepatocytes vacuolation, cloudy swelling and inflammatory cells infiltration induced by CCl4. Conclusion:, nm-haFGF had protective effects against H2O2 -induced hepatocyte injury in vitro and CCl4 -induced acute liver injury in vivo. [source] Single dose intravenous thioacetamide administration as a model of acute liver damage in ratsINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2008Tse-Min Chen Summary Thioacetamide (TAA) has been used extensively in the development of animal models of acute liver injury. Frequently, TAA is administered intraperitoneally to induce liver damage under anaesthesia. However, it is rarely administered by intravenous injection in conscious rats. The experiments in this study were designed to induce acute liver damage by single intravenous injection of TAA (0, 70 and 280 mg/kg) in unrestrained rats. Biochemical parameters and cytokines measured during the 60-h period following TAA administration, included white blood cells (WBC), haemoglobulin (Hb), platelet, aspartate transferase (GOT), alanine transferase (GPT), total bilirubin (TBIL), direct bilirubin (DBI), albumin, ammonia (NH3), r-glutamyl transpeptidase (r-GT), tumour necrosis factor-, (TNF-,) and interleukin-6 (IL-6). Rats were sacrificed by decapitation 60 h after TAA administration and livers were removed immediately for pathology and immunohistochemical (IHC) examination. Another group of rats were sacrificed by decapitation 1, 6 and 24 h after TAA administration and livers were removed immediately for time course change of pathology and IHC examination. TAA significantly increased blood WBC, GOT, GPT, TBIL, DBIL, NH3, r-GT, TNF-, and IL-6 levels but decreased the blood Hb, platelet and albumin level. The levels of histopathological damage in the liver after intravenous TAA administration were also increased with a dose-dependent trend and more increased at 60 h after TAA administration. The levels of inducible nitric oxide synthase (iNOS) and nuclear factor-,B (NF-,B) detected by IHC in the liver after intravenous TAA administration were also increased with a dose-dependent trend and more increased at 1 h after TAA administration. Single intravenous TAA administration without anaesthesia is a restorable animal model which may be used to investigate acute liver damage. [source] Vascular endothelial growth factor reduces Fas-mediated acute liver injury in miceJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7pt2 2008Yoichi Tanaka Abstract Background and Aim:, Fulminant hepatitis is still a fatal liver disease, and no specific treatment for it has been available. Vascular endothelial growth factor (VEGF) is the focus of attention because of its various actions. We investigated the effect of vascular endothelial growth factor (VEGF) on Fas-induced fulminant hepatic failure (FHF). Method:, Male Balb/c mice were treated with an intraperitoneal injection of an anti-Fas antibody (Jo-2 Ab) with or without premedication with intraperitoneally administered human recombinant VEGF. Results:, The serum level of alanine aminotransferase (ALT) was up to 300 times higher that of normal mice following the Jo-2 Ab injection, and histological analysis revealed hepatic injury and massive hepatocyte apoptosis. The VEGF significantly suppressed an elevation in serum ALT levels and hepatocyte apoptosis. Immunohistochemically, VEGF-treated mice showed that Bcl-xL in hepatocytes was strongly expressed. Conclusions:, Since hepatocytes do not express VEGF receptors, we speculated that VEGF acts on sinusoidal endothelial cells (SECs) and promotes production of cytokines such as hepatocyte growth factor in SECs, resulting in reducing apoptosis through an increase expression of Bcl-xL in hepatocytes. We suggest that VEGF has a potent antiapoptotic effect on hepatocytes through cell,cell interaction between SECs and hepatocytes. [source] Protective effect of total flavonoids from Bidens bipinnata L. against carbon tetrachloride-induced liver injury in miceJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2007Ming-mei Zhong Bidens bipinnata L. is well known in China as a traditional Chinese medicine. This study was designed to evaluate the hepatoprotective activity of the total flavonoids of B. bipinnata L. (TFB) against carbon tetrachloride (CCI4)-induced acute liver injury in mice and to determine its mechanism of action. Oral administration of TFB at doses of 50, 100 and 200 mg kg,1 for 7 days significantly reduced the elevated relative values of liver weight, serum transaminases (alanine aminotransferase and aspartate aminotransferase) and the hepatic morphologic changes induced by CCl4 in mice. In addition, TFB markedly inhibited CCl4 -induced lipid peroxidation and enhanced the activity of the antioxidant enzymes superoxide dismutase and glutathione peroxidase. Moreover, pretreatment with TFB suppressed nitric oxide production and nuclear factor- kB activation in CCl4 -treated mice. The results suggest that TFB has significant hepatoprotective activity and its mechanism is related, at least in part, to its antioxidant properties. Further research is required to investigate the detailed mechanism of the protective effect of TFB on acute liver injury. [source] In vivo study on the protection of indole-3-carbinol (I3C) against the mouse acute alcoholic liver injury by micro-Raman spectroscopyJOURNAL OF RAMAN SPECTROSCOPY, Issue 5 2009Aiguo Shen Abstract Micro-Raman spectroscopy (MRS) was utilized for the first time to evaluate the effect of indole-3-carbinol (I3C) on acute alcoholic liver injury in vivo. In situ Raman analysis of tissue sections provided distinct spectra that can be used to distinguish alcoholic liver injury as well as ethanol-induced liver fibrosis from the normal state. Sixteen mice with liver diseases including acute liver injury and chronic liver fibrosis, and eight mice with normal liver tissues, and eight remedial mice were studied employing the Raman spectroscopic technique in conjunction with biomedical assays. The biochemical changes in mouse liver tissue when liver injury/fibrosis occurs such as the loss of reduced glutathione (GSH), and the increase of collagen (,-helix protein) were observed by MRS. The intensity ratio of two Raman peaks (I1450/I666) and in combination with statistical analysis of the entire Raman spectrum was found capable of classifying liver tissues with different pathological features. Raman spectroscopy therefore is an important candidate for a nondestructive in vivo screening of the effect of drug treatment on liver disease, which potentially decreases the time-consuming clinical trials. Copyright © 2008 John Wiley & Sons, Ltd. [source] Long-term prognosis for transplant-free survivors of paracetamol-induced acute liver failureALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2010P. Jepsen Aliment Pharmacol Ther 2010; 32: 894,900 Summary Background, The prognosis for transplant-free survivors of paracetamol-induced acute liver failure remains unknown. Aim, To examine whether paracetamol-induced acute liver failure increases long-term mortality. Methods, We followed up all transplant-free survivors of paracetamol-induced acute liver injury, hospitalized in a Danish national referral centre during 1984,2004. We compared age-specific mortality rates from 1 year post-discharge through 2008 between those in whom the liver injury led to an acute liver failure and those in whom it did not. Results, We included 641 patients. On average, age-specific mortality rates were slightly higher for the 101 patients whose paracetamol-induced liver injury had caused an acute liver failure (adjusted mortality rate ratio = 1.70, 95% CI 1.02,2.85), but the association was age-dependent, and no survivors of acute liver failure died of liver disease, whereas suicides were frequent in both groups. These observations speak against long-term effects of acute liver failure. More likely, the elevated mortality rate ratio resulted from incomplete adjustment for the greater prevalence of substance abuse among survivors of acute liver failure. Conclusions, Paracetamol-induced acute liver failure did not affect long-term mortality. Clinical follow-up may be justified by the cause of the liver failure, but not by the liver failure itself. [source] Albumin dialysis in cirrhosis with superimposed acute liver injury: possible impact of albumin dialysis on hospitalization costsLIVER INTERNATIONAL, Issue 2003T. Hassanein Abstract Albumin dialysis using the Molecular Adsorbents Recirculating System (MARS) has been found to be beneficial in the treatment of cirrhotic patients with acute decompensation to improve survival as well as reduce associated complications. The present study attempts to analyze the costs involved, and compare it to the benefit as a result of the MARS therapy, thus evaluating its cost-effectiveness. Using the results of a study by Kim et al. (Hepatology 2001) describing the effects of complications on the cost of hospitalization in alcoholic liver disease patients, the expenditure incurred in a group of 11 patients treated with standard medical therapy (five survivors) and a group of 12 patients treated with MARS in addition (11 survivors) (Heemann et al., Hepatology 2002) were analyzed. MARS resulted in a reduction of in-hospital deaths, as well as liver disease-related complications. Both these factors led to a substantial reduction of costs in the MARS group, which was enough to counterbalance the extra costs associated with extra-corporeal therapy. In the control group, the total hospitalization cost per survivor were calculated to be at $35 904. In the MARS group, the overall expenditure per survivor including standard medical therapy plus additional MARS liver support therapy were $32 036 , a saving of nearly $4000 compared to the control group. Therefore, it appears that the benefits of MARS therapy are enough to justify the cost of treatment and safe hospital costs, at least in the described population. However, further studies are needed to confirm these results. [source] A novel role of alkaline phosphatase in protection from immunological liver injury in miceLIVER INTERNATIONAL, Issue 1 2002Qiang Xu Abstract:Aims/Background: Little is known about the role of alkaline phosphatase (AP) in liver diseases, except for its elevation in jaundice or cholestasis. Its substrate, endotoxin, is usually elevated in patients as well as animals with liver damage. This study aimed to provide evidence for its new role as protection against immunological liver damage. Methods: Liver injury was induced in mice by delayed-type hypersensitivity to picryl chloride. AP activity was measured using a commercial kit. Results: In acute liver injury, a significant decrease in AP activity in serum was observed but there was an increase in liver tissue. Single administration of cyclophosphamide before sensitization with picryl chloride exacerbated the liver injury, with more serious AP changes, while consecutive use after the sensitization alleviated the injury with a recovery from the changes. When liver injury proceeded for 1 week, both serum and liver showed decreased AP activity. Lipopolysaccharide facilitated alanine transaminase release from levamisole-pretreated but not non-treated hepatocytes from naive mice. However, the release was confirmed from liver slices of mice with liver injury proceeding for 1 week, even without levamisole pretreatment. Conclusion: The development of liver injury may lead to a dysfunction in AP synthesis and release. Levamisole may make normal hepatocytes, like the hepatocytes from liver-injured mice, highly sensitive to lipopolysaccharide through inhibiting AP synthesis. The findings obtained in this study suggest that AP may contribute to protection from injury by a mechanism involving neutralization of endotoxin. [source] The safety of rosuvastatin in comparison with other statins in over 100,000 statin users in UK primary care,,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 10 2008Luis Alberto García-Rodríguez MD Abstract Purpose To compare mortality and the incidence of hospitalization for myopathy, rhabdomyolysis, acute renal failure and acute liver injury in patients receiving rosuvastatin and those taking other statins. Methods Patients prescribed a statin that they had not used before were selected from the UK General Practice Research Database (GPRD) and followed up from 1 April 2003 to 31 December 2005. Results We studied 10,289 patients on rosuvastatin and 117,102 taking other statins. No cases of myopathy, rhabdomyolysis or acute liver injury occurred among rosuvastatin users. In those taking statins other than rosuvastatin, the incidence of myopathy was 0.4 (95% confidence interval (CI): 0.1,0.9), of rhabdomyolysis was 0.4 (95%CI: 0.1,0.9) and of acute liver injury was 0.4 (95%CI: 0.2,1.0), per 10,000 person-years. Fourteen cases of acute renal failure were identified (two among rosuvastatin users and 12 among other statin users). Among current users, the relative risk (RR) of acute renal failure in rosuvastatin users compared with other statin users was 1.16 (95%CI: 0.15,9.03). We identified 3232 deaths during the study period (173 in the rosuvastatin-treated group and 3059 in the other statin group). The RR of death associated with current use of rosuvastatin compared with other statins was 0.55 (95%CI: 0.44,0.68). Conclusions We found no evidence that patients prescribed rosuvastatin were at greater risk of these outcomes than patients prescribed other statins. There was no evidence of increased mortality among patients taking rosuvastatin, even after allowing for age, sex and prior statin use. Copyright © 2008 John Wiley & Sons, Ltd. [source] The safety of rosuvastatin in comparison with other statins in over 25,000 statin users in the Saskatchewan Health Databases,,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 10 2008Luis Alberto García-Rodríguez MD Abstract Purpose To compare mortality and the incidence of hospitalization for myopathy, rhabdomyolysis, acute renal failure and acute liver injury in patients receiving rosuvastatin and those taking other statins. Methods Patients prescribed a statin that they had not used before were selected from the Saskatchewan Health Databases (SHD) and followed up from 1 July 2003 until 31 March 2005. Results We studied 10,384 patients on rosuvastatin and 14,854 taking other statins. Two cases of myopathy were identified (one on rosuvastatin, one on another statin). The relative risk (RR) of myopathy in patients currently taking rosuvastatin compared with other statins was 1.31 (95% confidence interval [CI]: 0.13,13.41). Two cases of rhabdomyolysis were detected among current rosuvastatin users (incidence: 2.9 [95% CI: 0.8,10.7] per 10,000 person-years). No cases of acute liver injury occurred among rosuvastatin patients. Seventeen cases of acute renal failure were identified (five among rosuvastatin users, 12 taking other statins). The RR of acute renal failure in current rosuvastatin users compared with other statins was 0.49 (95% CI: 0.16,1.50). We identified 285 deaths during the study period (87 among rosuvastatin users, 198 taking other statins). The RR of death in current rosuvastatin users compared with other statins was 0.42 (95% CI: 0.32,0.57). Conclusions We found no evidence that patients prescribed rosuvastatin were at greater risk of the study outcomes than patients prescribed other statins. There was no evidence of increased mortality among patients taking rosuvastatin, even after allowing for age, sex and prior statin use. Copyright © 2008 John Wiley & Sons, Ltd. [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] Chemoprotective effects of a protein from the red algae Porphyra yezoensis on acetaminophen-induced liver injury in ratsPHYTOTHERAPY RESEARCH, Issue 9 2008Hye-Jung Hwang Abstract Seaweeds contribute to the maintenance of health through their nutritional and medicinal properties. The effects of PYP, a 14 kDa protein isolated from a hot-water extract of the marine alga Porphyra yezoensis, on AAP-induced liver injury in rats was evaluated. AAP induced acute liver injury and AAP-induced hepatotoxicity is the leading cause of liver failure. In this study, male Sprague,Dawley rats were assigned to one of three treatment groups: control, AAP, or AAP + PYP. Compared with the control group, liver tissue from the AAP group showed increased levels of caspase-3 activity and DNA fragmentation, decreased levels of GSH and increased serum GOT/GPT levels. In contrast, treatment with AAP + PYP produced levels of caspase-3 activity, DNA fragmentation, GSH and GOT/GPT that matched the values seen in the control group. It is concluded that PYP may prevent AAP-induced liver injury. Copyright © 2008 John Wiley & Sons, Ltd. [source] Antioxidative effects of pumpkin seed (Cucurbita pepo) protein isolate in CCl4-Induced liver injury in low-protein fed ratsPHYTOTHERAPY RESEARCH, Issue 11 2006C. Z. Nkosi Abstract The effects of pumpkin seed (Cucurbita pepo) protein isolate on the plasma activity levels of catalase (CA), superoxide dismutase (SOD), glutathione peroxidase (GSHpx) and total antioxidant capacity (TAC) as well as glucose-6-phosphatase (G6Pase) in liver homogenates and lipid peroxidation (LPO-malondialdehyde-MDA) levels in liver homogenates and liver microsomal fractions against carbon tetrachloride (CCl4)-induced acute liver injury in low-protein fed Sprague-Dawley rats (Rattus norvegicus) were investigated. A group of male Sprague-Dawley rats maintained on a low-protein diet for 5 days were divided into three subgroups. Two subgroups were injected with carbon tetrachloride and the other group with an equivalent amount of olive oil. Two hours after CCl4 intoxication one of the two subgroups was administered with pumpkin seed protein isolate and thereafter switched onto a 20% pumpkin seed protein isolate diet. The other two groups of rats were maintained on the low-protein diet for the duration of the investigation. Groups of rats from the different subgroups were killed at 24, 48 and 72 h after their respective treatments. After 5 days on the low-protein diet the activity levels of all the enzymes as well as antioxidant levels were significantly lower than their counterparts on a normal balanced diet. However, a low-protein diet resulted in significantly increased levels of lipid peroxidation. The CCl4 intoxicated rats responded in a similar way, regarding all the variables investigated, to their counterparts on a low-protein diet. The administration of pumpkin seed protein isolate after CCl4 intoxication resulted in significantly increased levels of all the variables investigated, with the exception of the lipid peroxidation levels which were significantly decreased. From the results of the present study it is concluded that pumpkin seed protein isolate administration was effective in alleviating the detrimental effects associated with protein malnutrition and CCl4 intoxication. It is therefore apparent that pumpkin seed protein isolate has components that have antiperoxidative properties. Copyright © 2006 John Wiley & Sons, Ltd. [source] Effect of pumpkin seed (Cucurbita pepo) protein isolate on the activity levels of certain plasma enzymes in CCl4 -induced liver injury in low-protein fed ratsPHYTOTHERAPY RESEARCH, Issue 4 2005C. Z. Nkosi Abstract The effects of pumpkin seed (Cucurbita pepo) protein isolate on the activity levels of lactate dehydrogenase (LD), alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) against carbon tetrachloride (CCl4)-induced acute liver injury in low-protein fed rats were investigated. A group of male Sprague-Dawley rats maintained on a low-protein diet for 5 days were divided into three subgroups. Two subgroups were injected with carbon tetrachloride and the other group with an equivalent amount of olive oil. Two hours after CCl4 intoxication one of the two subgroups was administered with pumpkin seed protein isolate. All three subgroups of rats were maintained on the low-protein diet for the duration of the investigation. Groups of rats from the different subgroups were killed at 24, 48 and 72 h after their respective treatments. After 5 days on the low-protein diet the activity levels of all four enzymes were significantly higher than their counterparts on a normal balanced diet. CCl4 intoxication resulted in significant increases in the activity levels of all four enzymes investigated. The administration of pumpkin seed protein isolate after CCl4 intoxication resulted in significantly reduced activity levels of all four enzymes. It is concluded that pumpkin seed protein isolate administration was effective in alleviating the detrimental effects associated with protein malnutrition. Copyright © 2005 John Wiley & Sons, Ltd. [source] Acute Hepatitis Associated with Treatment of Peyronie's Disease with Potassium Para-Aminobenzoate (Potaba)THE JOURNAL OF SEXUAL MEDICINE, Issue 12 2008Joey Roy ABSTRACT Introduction., Potassium para-aminobenzoate is an agent used in the treatment of sclerotic diseases including Peyronie's disease of the penis. It has been reported that this medication may have been responsible for cases of acute liver injury. Aim., To inform clinicians of the possibility of an adverse drug event associated with the oral intake of potassium para-aminobenzoate by reporting an additional case and compiling information from previous reports. Methods., The affected patient's medical records were diligently reviewed; all available and relevant information pertaining to this adverse event is reported. Similar case reports were analyzed and compared, and relevant information was compiled in this report. Results., The patient enjoyed a full biochemical recovery from his hepatitis 4 months after discontinuation of potassium para-aminobenzoate. Conclusion., To date, the oral use of potassium para-aminobenzoate has been reported to be linked to acute liver injury in six individuals. Appropriate management of this adverse drug event is the immediate discontinuation of the offending drug and general patient support measures. Roy J, and Carrier S. Acute hepatitis associated with treatment of Peyronie's disease with potassium para-aminobenzoate (Potaba). J Sex Med **;**:**,**. [source] The effects of dietary flaxseed on the Fischer 344 rat.CELL BIOCHEMISTRY AND FUNCTION, Issue 6 2005Abstract The hepatotoxic effect of carbon tetrachloride (CCl4) administered by gavage at 0.25,ml CCl4 (1:1 in olive oil) per 100,g body weight was examined 24,h later in regular chow fed (RC) and 10% flax chow fed (FC) male and female Fischer 344 rats. CCl4 -treated RC rats were subdued, lethargic and unkempt. CCl4 -treated FC rats were much less affected. CCl4 treatment resulted in loss of weight in RC and FC rats. In males, the weight loss was 6.7% body mass in RC rats compared to 5.6% body mass in FC rats. In females, the weight loss was 7.5% body mass in both RC and FC rats. While CCl4 treatment increased the level of the liver injury marker plasma alanine aminotransferase (ALT) in RC rats, this CCl4 effect was significantly attenuated in FC rats. In male rats, the ALT increase was 435-fold in RC rats and 119-fold in FC rats, over that of their respective controls. In female rats, the ALT increase was 454-fold in RC rats and 381-fold in FC rats, over that of their respective controls. These results provide evidence that flax consumption protects the liver against injury and that the extent of the protection is sex dependent. CCl4 had no effect on the plasma level of ,-glutamyltranspeptidase (,GT) in RC and FC rats supporting the contention that plasma ,GT is not a useful marker for acute liver injury which is seen in this model. The activity of ,GT was increased in the livers of FC rats compared to RC rats: 2.7-fold in males and 1.5-fold in females. In RC rats, the activity of liver ,GT was decreased by CCl4 treatment: 70% in the male and 25% in the female. However, this CCl4 effect was reversed or abolished by flax consumption. Compared to RC rats: in male FC rats, CCl4 actually increased the activity of liver ,GT 1.28-fold; while in female FC rats, the depressing effect of CCl4 treatment was abolished. The flax-induced preservation of ,GT in the liver in response to injury may be involved in the observed hepatoprotection through generation of GSH. In RC male rats, CCl4 treatment effected a 25% reduction in plasma glucose levels. There was no decrease in CCl4 -treated FC male rats. In female rats, CCl4 treatment effected a 21% decrease in plasma glucose levels in both RC and FC rats. In conclusion, multiple parameters for acute CCl4 -induced injury were attenuated in the FC compared to the RC rat. That flaxseed consumption conferred greater protection against liver injury in the male than in the female suggests an involvement of the estrogenic lignan component of flaxseed. We discuss the possibility that this hepatoprotection is through a flax lignan-induced increase in reduced glutathione related to a flax effect on the activity of liver ,GT in the resting state and the maintenance of its activity in response to injury. Copyright © 2005 John Wiley & Sons, Ltd. 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