allopurinol and Hepatitis

Topics: Allopurinol; Chemical and Drug Induced Liver Injury; Cholestasis; Chronic Disease; Female; Granuloma; Hepatitis; Humans; Indoles; Liver Cirrhosis; Methyldopa; Nitrofurantoin; Oxyphenisatin Acetate; Phenylbutazone

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver-related morbidity and mortality disease in the world. However, no effective pharmacological treatment for NAFLD has been found. In this study, we used a high fat diet (HFD)-induced NAFLD model to investigate hepatoprotective effect of apigenin (API) against NAFLD and further explored its potential mechanism. Our results demonstrated that gavage administration of API could mitigate HFD-induced liver injury, enhance insulin sensitivity and markedly reduce lipid accumulation in HFD-fed mice livers. In addition, histological analysis showed that hepatic steatosis and macrophages recruitment in the API treatment group were recovered compared with mice fed with HFD alone. Importantly, API could reverse the HFD-induced activation of the NLRP3 inflammasome, further reduced inflammatory cytokines IL-1β and IL-18 release, accompanied with the inhibition of xanthine oxidase (XO) activity and the reduction of uric acid and reactive oxygen species (ROS) production. The pharmacological role of API was further confirmed using free fatty acid (FFA) induced cell NAFLD model. Taking together, our results demonstrated that API could protect against HFD-induced NAFLD by ameliorating hepatic lipid accumulation and inflammation. These protective effects may be partially attributed to the regulation of XO by API, which further modulated NLRP3 inflammasome activation and inflammatory cytokines IL-1β and IL-18 release. Therefore API is a potential therapeutic agent for the prevention of NAFLD.

Topics: Animals; Apigenin; Diet, High-Fat; Gene Expression Regulation; Glucose; Hepatitis; Inflammasomes; Lipid Metabolism; Liver; Macrophages; Male; Mice, Inbred C57BL; NLR Family, Pyrin Domain-Containing 3 Protein; Non-alcoholic Fatty Liver Disease; Weight Gain; Xanthine Oxidase

The objective of this study was to demonstrate the clinical profiles of Stevens-Johnson syndrome (SJS) in Thai patients, and to compare those clinical features between younger and older patients. Medical records of all patients with SJS who were admitted to Srinagarind Hospital Medical School, Khon Kaen, Thailand, from January 2002 to December 2014 were reviewed. Epidemiological features, etiologies, treatment and clinical outcomes were collected. There were 45 patients with SJS during the 10-year period. Females were the majority (57.8%) and the median age was 49 years. Hepatitis was the most frequent complication (67.5%). Phenytoin (15.6%), sulfonamide drugs (15.6%) and allopurinol (13.3%) were implicated as leading causes of SJS. Steroids were prescribed in 37 cases (82.2%). The mortality rate was 4.4%. Comparing older patients to younger patients, allopurinol appeared to be the main instigating drug to develop SJS with an odds ratio of 5.6 (95% confidence interval, 2.8-10.6). In conclusion, clinical features of Thai patients with SJS were similar to other reports. Allopurinol had the strongest association with SJS in older patients as compared to the younger ones.

Topics: Adolescent; Adult; Age Factors; Aged; Allopurinol; Female; Hepatitis; Humans; Male; Middle Aged; Phenytoin; Retrospective Studies; Stevens-Johnson Syndrome; Sulfonamides; Thailand; Young Adult

Hepatic ischemia/reperfusion (I/R) injury significantly influences short-term and long-term outcomes after liver transplantation (LTx). The critical step initiating the injury is known to include sinusoidal endothelial cell (SEC) alteration during the cold preservation period. As carbon monoxide (CO) has potent cytoprotective functions on vascular endothelial cells, this study examined if CO treatment of excised liver grafts during cold storage could protect SECs and ameliorate hepatic I/R injury. Rat liver grafts were preserved in University of Wisconsin (UW) solution containing 5% CO (CO-UW solution) for 18 to 24 hours and were transplanted into syngeneic Lewis rats. After 18 hours of cold preservation, SEC damage was evident with propidium iodide (PI) nuclear staining on SECs, and the frequency of PI(+) SECs was significantly lower in grafts stored in CO-UW solution versus those stored in control UW solution. SEC protection with CO was associated with decreased intercellular cell adhesion molecule translocation and less matrix metalloproteinase release during cold preservation. After LTx with 18 hours of cold preservation, serum alanine aminotransferase levels and hepatic necrosis were significantly less in the CO-UW group than in the control UW group. With 24 hours of cold storage, 35% (7/20) survived with control UW solution, whereas the survival with CO-UW solution improved to 80% (8/10). These beneficial effects of CO-UW solution were associated with a significant reduction of neutrophil extravasation, down-regulation of hepatic messenger RNA for tumor necrosis factor alpha and intercellular cell adhesion molecule 1, and less hepatic extracellular signal-regulated kinase activation. Liver grafts from Kupffer cell-depleted donors or pseudogerm-free donors showed less SEC death during cold preservation, and CO-UW solution further reduced SEC death. In conclusion, CO delivery to excised liver grafts during cold preservation efficiently ameliorates SEC damage and hepatic I/R injury.

Topics: Adenosine; Allopurinol; Animals; Carbon Monoxide; Cryopreservation; Cryoprotective Agents; Endothelial Cells; Glutathione; Graft Survival; Hepatitis; Insulin; Kupffer Cells; Liver Transplantation; Male; MAP Kinase Signaling System; Matrix Metalloproteinases; Neutrophils; Organ Preservation; Organ Preservation Solutions; Primary Graft Dysfunction; Raffinose; Rats; Rats, Inbred Lew; Reperfusion Injury

Oxidative stress is an important pathophysiological mechanism in non-alcoholic steatohepatitis (NASH). We aimed to evaluate serum xanthine oxidase (XO) (as a generator of reactive oxygen species), superoxide dismutase (SOD), glutathione peroxidase (GSHPx), paraoxonase (PON1) activities, nitric oxide (NO) and thiol levels in patients with NASH.. A total of 35 patients with NASH and 31 age-and-gender-matched healthy subjects were enrolled in the study as control group. Serum levels of XO, NO, SOD, GSHPx, PON1 and thiol were determined by spectrophotometric methods.. Serum XO activities were higher in the patients with NASH than the controls (p<0.001). Serum NO levels, SOD, GSHPx, PON1 activities and thiol levels were lower in the patients with NASH than the controls (p<0.031, p<0.019, p<0.001, p<0.001, p<0.001, respectively).. Increased oxidative stress in patients with NASH may result in a pro-oxidation environment, which in turn could result in decreased antioxidant enzyme activities and NO levels. Therefore effective antioxidant therapy to inhibit oxidative stress is necessary and agents to increase antioxidant enzyme may be a therapeutic option in NASH.

Topics: Adult; Alcohols; Antioxidants; Aryldialkylphosphatase; Female; Glutathione Peroxidase; Hepatitis; Humans; Male; Nitric Oxide; Oxidative Stress; Superoxide Dismutase; Xanthine Oxidase

Allopurinol may induce severe hypersensitivity characterized by hepatitis, interstitial nephritis, and skin rash. The mechanisms for this hypersensitivity syndrome are incompletely elucidated. Immunologic studies were performed on tissue and peripheral blood lymphocytes from a patient with allopurinol hypersensitivity. Immunohistochemistry was performed on sections of the liver biopsy utilizing monoclonal antibodies for T and B lymphocytes. Peripheral blood lymphocyte immunophenotyping by flow cytometry and peripheral blood lymphocyte stimulation studies with either allopurinol or oxypurinol measured as tritiated thymidine uptake were performed in the hypersensitive patient and compared to a group of six patients treated with allopurinol without hypersensitivity and eight normal control patients. Additional single- and dual-color immunophenotyping by flow cytometry of oxypurinol-stimulated lymphocytes was performed in the hypersensitive patient and compared to normal controls. The liver biopsy demonstrated predominantly a T lymphocyte infiltrate. The number of peripheral blood lymphocytes expressing activation antigens was significantly greater in the hypersensitive patient compared to that of both control groups. Lymphocytes from the hypersensitive patient were moderately stimulated by allopurinol and markedly stimulated by oxypurinol compared to both control groups. Oxypurinol-stimulated lymphocytes from the hypersensitive patient demonstrated enhanced expression of activation antigens compared to unstimulated lymphocytes from this patient and normal controls. These studies suggest that cell-mediated immunity directed toward allopurinol and more importantly to its oxypurinol metabolite is involved in the pathogenesis of allopurinol-induced hypersensitivity.

Topics: Acute Disease; Allopurinol; Drug Hypersensitivity; Female; Hepatitis; Humans; Immunity, Cellular; Immunophenotyping; Lymphocyte Activation; Middle Aged

Frozen section examination was performed on 385 donor livers before transplantation. Exclusion criteria were applied to the donor livers examined to exclude potentially dysfunctional livers. The exclusion criteria included the following: severe macrovesicular steatosis, ischemic necrosis, prominent chronic portal inflammation, prominent periductular fibrosis, granulomatous inflammation, bridging fibrosis, and malignancy. Twenty-seven of the 385 donor livers examined were excluded before transplantation. The following histologic features were present in the excluded livers: severe steatosis (22), ischemic necrosis (2), portal inflammation (1), and periductular fibrosis (2). Steatosis was present in 51 of the 385 (13.25%) organs examined, including 22 of the donor organs excluded before transplantation. Twenty-nine livers with mild to moderate steatosis were implanted into size and blood type-matched recipients. Indicators of allograft function (prothrombin time and bilirubin) and damage (aspartate aminotransferase and alanine aminotransferase) were measured daily for the first 10 days after transplant. There was no statistically significant difference between the group of nonfat livers and donor livers containing mild steatosis. Statistically significant higher posttransplant serum alanine aminotransferase and prothrombin time levels were present in the patients with livers implanted with mild versus moderate steatosis. The 1-year survival rate for patients receiving fatty versus nonfatty donor livers was not statistically different (Kaplan-Meier, P = 0.592). No significant differences were found in the clinical and laboratory characteristics of donors whose organs were implanted compared with the clinical and laboratory characteristics of donors whose organs were excluded. The primary nonfunction rate after applying the exclusion criteria was 1.4%, which is a significant decrease compared with our primary nonfunction rate of 8.5% before using frozen section examination. Frozen section examination is useful in excluding donor organs which may become dysfunctional after transplantation.

Topics: Adenosine; Adult; Allopurinol; Azo Compounds; Child; Fatty Liver; Female; Fibrosis; Frozen Sections; Glutathione; Hepatitis; Humans; Hypertonic Solutions; Insulin; Ischemia; Liver; Liver Transplantation; Male; Necrosis; Organ Preservation; Organ Preservation Solutions; Raffinose; Staining and Labeling; Survival Rate; Tissue Donors

The role of platelet-activating factor as a potential mediator of hepatic inflammatory injury associated with liver ischemia/reperfusion was investigated using a partial no-flow model in rats in vivo. Platelet-activating factor levels of livers from sham-operated rats and from animals experiencing hepatic reperfusion for less than 6 hr were very low. They were observed to increase significantly after 12 hr of reperfusion and reached peak levels after a 24-hr reperfusion period, a time when maximal hepatic injury and inflammation occurred. Treatment of experimental rats with WEB2170, a platelet-activating factor receptor antagonist, attenuated the hepatic injury and inflammation, as evidenced by decreases in plasma ALT and in hepatocyte necrosis and neutrophil infiltration. Both inactivation of Kupffer cells with gadolinium chloride and inhibition of the formation of reactive oxygen species with allopurinol reduced platelet-activating factor production in the liver, whereas induction of neutropenia had no effect, suggesting that interaction of Kupffer cells with oxygen-derived free radicals may be a plausible mechanism for hepatic platelet-activating factor accumulation. It is concluded that platelet-activating factor contributes to the inflammatory consequences of ischemia/reperfusion underlying late-phase hepatic injury.

Topics: Alanine Transaminase; Allopurinol; Animals; Azepines; Gadolinium; Hepatitis; Ischemia; Leukocytes; Liver; Male; Necrosis; Platelet Activating Factor; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Triazoles

We have investigated the possible protective effect of superoxide dismutase and allopurinol in a rat model of mild and severe hepatic necrosis produced by Corynebacterium parvum with or without endotoxin. Histology showed a sinusoidal mononuclear cell infiltrate with multiple granulomata but variable degrees of hepatic necrosis. In the severe hepatic injury model there was a reduction in mortality, associated with a decrease in histologic and biochemical evidence of hepatic necrosis, after treatment with superoxide dismutase. This protective effect was not demonstrated with partially heat-inactivated superoxide dismutase. In the mild hepatic injury model similar trends in reduction of serum levels of hepatic enzymes were observed after treatment with both superoxide dismutase and allopurinol. These results indicate that oxygen-derived free radicals may play an important role in the pathogenesis of hepatic injury in the rat.

Topics: Alanine Transaminase; Allopurinol; Animals; Disease Models, Animal; Endotoxins; Free Radicals; Hepatitis; Isocitrate Dehydrogenase; Liver; Liver Diseases; Necrosis; Propionibacterium acnes; Rats; Rats, Inbred Strains; Superoxide Dismutase; Superoxides; Xanthine Oxidase

Xanthine oxidase activity: O2-dependent and NAD+-dependent forms, were carried out in cytosol supernatant of Rat liver homogenat with adjuvant and hepatocytes induced arthritis and hepatitis. Both forms were increased without modification of their ratio. These results suggest that xanthine oxidase was implicated in the inflammatory reaction.

Topics: Aerobiosis; Animals; Arthritis; Arthritis, Experimental; Cytosol; Disease Models, Animal; Hepatitis; Liver; Male; NAD; Oxygen; Rats; Rats, Inbred Strains; Xanthine Oxidase

Topics: Arginase; Biopsy; Child; Child, Preschool; Chronic Disease; Female; Hepatitis; Humans; Infant; Infant, Newborn; Infections; Liver; Liver Cirrhosis; Liver Diseases; Male; Nephrotic Syndrome; Nutrition Disorders; Xanthine Oxidase

Topics: Alanine Transaminase; Alkaline Phosphatase; Anemia, Hemolytic; Aspartate Aminotransferases; Carbon Isotopes; Cholestasis; Female; Hepatitis; Humans; Infectious Mononucleosis; Liver Cirrhosis; Liver Diseases; Male; Myocardial Infarction; Neoplasms; Typhoid Fever; Xanthine Oxidase

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Cholestasis; Chromatography, Gel; Female; Hemochromatosis; Hepatic Encephalopathy; Hepatitis; Hepatitis A; Humans; Intestinal Diseases; Liver Cirrhosis; Liver Diseases; Male; Myocardial Infarction; Rats; Spectrophotometry; Xanthine Oxidase

Topics: Alanine Transaminase; Aspartate Aminotransferases; Clinical Enzyme Tests; Diagnosis; Hepatitis; Hepatitis A; Humans; Jaundice; Jaundice, Obstructive; Liver Cirrhosis; Liver Diseases; Liver Function Tests; Myocardial Infarction; Statistics as Topic; Xanthine Oxidase

Topics: Blood Chemical Analysis; Carbon Isotopes; Chemistry Techniques, Analytical; Communicable Diseases; Hepatitis; Hepatitis A; Humans; Ion Exchange Resins; Oxidation-Reduction; Uric Acid; Xanthine Oxidase

Topics: Aminohydrolases; Blood Chemical Analysis; Borates; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Dogs; Guanine; Guanine Deaminase; Hepatitis; Research; Spectrophotometry; Toxicology; Xanthine Oxidase; Xanthines