allopurinol and Hepatic-Encephalopathy

Hepatic encephalopathy (HE) is a debilitating neurological complication of chronic liver disease (CLD). Hyperammonemia plays an important role in HE's pathogenesis, acting synergistically with systemic oxidative stress. During CLD, muscle plays a compensatory role in detoxifying ammonia, and therefore muscle loss leads to an increase in the risk of developing HE. With most animal studies involving males, sex's impact on the development of CLD and associated complications such as HE and muscle loss remains unknown. Therefore, we aimed to identify the impact of sex on CLD, HE, and muscle mass loss in a rodent model of CLD. Liver injury markers, hyperammonemia, oxidative stress, muscle mass, and ammonia clearance were measured in female and male bile-duct ligated (BDL) rats. In addition, covert HE was assessed in females while ammonia-precipitated severe HE was assessed in female and male BDL rats, and male BDL rats treated with allopurinol (100 mg/kg), an antioxidant (xanthine oxidase inhibitor). Female BDL developed CLD and HE (impaired motor coordination and night activity) compared to respective SHAM. Hyperammonemia and muscle ammonia clearance were similar between female and male BDL. However, only female BDL rats did not develop muscle loss, brain edema, and short-term memory impairment (vs. female SHAM) and systemic oxidative stress and decreased albumin levels (vs. male BDL). Furthermore, both female BDL and allopurinol-treated male BDL rats were protected against ammonia-induced overt HE. In conclusion, female and male BDL rats develop distinct features of CLD and HE, with systemic oxidative stress playing a pivotal role in the susceptibility to ammonia-precipitated overt HE.

Topics: Allopurinol; Ammonia; Animals; Bile; Disease Models, Animal; Female; Hepatic Encephalopathy; Hyperammonemia; Male; Oxidative Stress; Rats

Ammonia is considered to be the main agent responsible for hepatic encephalopathy which progressively leads to altered mental status. N-methyl-D-aspartate (NMDA) is an ionotropic glutamate receptor, which is involved in synaptogenesis, memory and neurotoxicity. The aim of this study was to investigate the effects of ammonia intoxication and allopurinol, a xanthine oxidase (XO) inhibitor, on NMDA receptor subunits, NR2A and NR2B, in the hippocampus of rats. Thirty-six male rats were divided into three groups (n = 12/group) as follows: (1)control group (phosphate buffered saline (PBS) solution); (2)ammonia group (ammonium acetate, 2.5 mmol/kg), (3)ammonia + allopurinol group (ammonium acetate, 2.5 mmol/kg, allopurinol, 50 mg/kg). Each rat received intraperitoneal injection for 28 days. Western Blotting technique was used for detecting NR2A and NR2B expressions. Both NR2A and NR2B subunit expressions decreased 27 and 11%, respectively, in ammonia group with respect to the control group. Ammonium acetate decreased significantly in NR2A subunit expressions in the hippocampus (p < 0.01). Administration of ammonia + allopurinol caused statistically significant increases in NR2A subunit expressions compared to the ammonia group (p < 0.001). The down-regulation of NMDA receptors caused by ammonium acetate suggest that these receptors may play role in the process of hepatic encephalopathy and using allopurinol may have some protective effects in ammonia toxicity.

Topics: Acetates; Allopurinol; Animals; Down-Regulation; Hepatic Encephalopathy; Hippocampus; Male; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate

The experience with 52 episodes of visceral leishmaniasis diagnosed in 43 patients is reported. The most common symptoms were fever (81%), splenomegaly (65%), hepatomegaly (63%), and pancytopenia (73%). In 79% of the patients, CD4+ cell counts were < 100 cells/mm3. Prior or simultaneous diagnosis of AIDS was made in 29 (67%) patients. Diagnosis was considered fortuitous in 19% of the episodes. In 27% of the episodes, the diagnosis was made on the basis of demonstration of parasites outside the reticuloendothelial system, chiefly blood (7 cases) and gastrointestinal mucosa (5 cases). Parasites were frequently observed or cultured from blood (22/37 episodes) or the digestive tract (8/9 episodes). High antimony doses were more effective than low doses in achieving clinical or parasitological cure (rate of cure, 80% vs. 40%, p = 0.11). Severe toxicity was observed in six (11.7%) of the 51 treated episodes. Severe AIDS-related diseases [odds ratio (OR) 10, p < 0.05] and CD4+ counts (OR 12, p < 0.05) were independent factors for early death. Prophylaxis with monthly pentamidine was not useful in reducing relapses of visceral leishmaniasis.

Topics: AIDS-Related Opportunistic Infections; Allopurinol; Amebicides; Amphotericin B; Analysis of Variance; Anti-HIV Agents; Antimetabolites; Antimony; Antiprotozoal Agents; Blood; Bone Marrow; CD4-Positive T-Lymphocytes; Cerebrospinal Fluid; Didanosine; Digestive System; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Hepatic Encephalopathy; HIV; Humans; Intestinal Mucosa; Leishmaniasis, Visceral; Lymphocyte Count; Male; Myocarditis; Neutrophils; Pancreatitis; Pentamidine; Renal Insufficiency; Spain; Zidovudine

A 58-year-old Chinese woman was admitted to hospital with a presumed hypersensitivity reaction to allopurinol. Her illness was characterised by high fever, eosinophilia, exfoliative dermatitis and jaundice. She developed fulminant hepatic failure and septicemia with a fatal outcome. Clinical details are presented and the possible relationship of allopurinol hypersensitivity to renal impairment is discussed.

Topics: Allopurinol; Drug Hypersensitivity; Female; Hepatic Encephalopathy; Humans; Liver; Middle Aged

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