allopurinol and Liver-Failure--Acute

The dynamics of cytopathic hypoxia markers in patients with acute pancreatitis (AP) biliary etiology (BE), depending on the presence of concomitant diabetes mellitus (DM), which is an independent factor of premorbid severity increase and increase in the degree of operational and anesthetic risk. Markers of cytopathic hypoxia use as methods for early diagnosis of acute liver failure (ALF) and monitoring the effectiveness of its correction promising. In terms of cytopathic hypoxia may be at the stage of laboratory diagnostics to distinguish between destructive and non-destructive forms APBE, and for markers of endothelial dysfunction--destructive forms on the area and depth of destruction of the pancreas.

Topics: Adenosine Deaminase; Adult; Aged; Arginine; Biomarkers; Case-Control Studies; Common Bile Duct; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoxia; Liver; Liver Failure, Acute; Male; Middle Aged; Pancreas; Pancreatitis, Acute Necrotizing; Severity of Illness Index; Xanthine Dehydrogenase; Xanthine Oxidase

Oxidative stress plays important role in the development of acute liver failure. In this study, we investigated effects of allopurinol (AP) upon thioacetamide (TAA)-induced liver injury and the potential mechanisms leading to amelioration in inflammation with AP treatment. Acute liver failure was induced by intraperitoneal administration of TAA (300 mg/kg/day for 2 days). Thirty-five rats were divided into five groups as control (group 1), TAA (group 2), TAA + 25AP (group 3), TAA + 50 AP (group 4), and TAA + 100AP (group 5). The number of animals in each group was seven. At the end of the study, histopathological, biochemical, and western blot analysis were done. TAA treatment significantly increased serum levels of aminotransferases, liver malondialdehyde (MDA), nuclear factor-kappa B (NF-қB ), activator protein-1 (AP-1), tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6) levels, and the necro-inflammation scores. Nevertheless, nuclear factor E2-related factor-2 and heme oxygenase-1 (HO-1) expressions in the liver were decreased by TAA. AP treatment significantly lowered the serum levels of aminotransferases (P < 0.01) and liver MDA, NF-κB, AP-1, TNF-α, COX-2, and IL-6 expressions (P < 0.05). Moreover, AP restored the liver Nrf2 and HO-1 expressions and improved the necro-inflammation scores significantly. AP improves oxidative stress-induced liver damage by regulating cellular redox-sensitive transcriptor factors and expression of pro-inflammatory and antioxidant defense mechanisms. AP probably exerts these beneficiary features by its free radical scavenging ability in a dose-dependent manner.

Topics: Allopurinol; Animals; Antioxidants; Chemical and Drug Induced Liver Injury; Cyclooxygenase 2; Heme Oxygenase-1; Inflammation; Interleukin-6; Liver Failure, Acute; Male; Malondialdehyde; NF-E2-Related Factor 2; NF-kappa B; Oxidation-Reduction; Oxidative Stress; Rats; Rats, Wistar; Reactive Oxygen Species; Thioacetamide; Transaminases; Transcription Factor AP-1; Transcription Factors; Tumor Necrosis Factor-alpha

Topics: Adrenal Cortex Hormones; Adrenergic beta-Agonists; Aged; Allopurinol; Angioedema; Diuretics; Drug Hypersensitivity; Exanthema; Gout; Histamine Antagonists; Humans; Hypertension; Hyperuricemia; Liver Failure, Acute; Male; Oxygen Inhalation Therapy; Renal Insufficiency

Hyperuricemia is present in about 5% of the population, and allopurinol is frequently used to treat it. The use of this drug can be associated with a number of side effects, indicating allergic reactions, such as skin rash, reversible after its withdrawal. In some cases more severe hypersensitivity reactions may be seen, such as erythema multiforme exudativum, or Steven-Johnson Syndrome (SJS). Reversible clinical hepatotoxicity, as well as acute renal failure, may also develop after allopurinol therapy. We describe here the case of a 74-year-old woman with chronic renal failure who was admitted to hospital after 1 week of sore throat and fever, presenting mucous membrane lesions, widespread blistering of the skin, evolving to flaccid vesicles and bullae, and extensive epidermal detachment associated with acute renal failure and cholestatic jaundice. A diagnosis of allopurinol-induced toxic epidermal necrolysis (TEN) was established. Allopurinol was discontinued, and intensive care management was required: the patient was successfully treated by using intravenous immunoglobulin (IVIg), standard hemodialysis, and albumin dialysis (Molecular Adsorbents Recirculating System - MARS, Teraklin AG, Rostock, Germany). Allopurinol-induced TEN is extremely rare, however, the survival rate is extremely low. Clinicians should be aware of this potentially severe adverse effect. This report emphasizes the importance of an aggressive pharmacological and dialysis treatment in the case of TEN.

Topics: Acute Kidney Injury; Aged; Allopurinol; Biopsy; Female; Follow-Up Studies; Gout Suppressants; Humans; Hyperuricemia; Liver Failure, Acute; Risk Factors; Skin; Stevens-Johnson Syndrome