salicylates and Carbon-Tetrachloride-Poisoning

Topics: Acetaminophen; Adult; Alcohols; Aniline Compounds; Arsenic Poisoning; Barbiturates; Carbon Tetrachloride Poisoning; Chelating Agents; Child; Chloral Hydrate; Fluoride Poisoning; Glutethimide; Glycols; Humans; Infant; Iron; Lead Poisoning; Male; Mercury Poisoning; Methaqualone; Phenacetin; Poisoning; Renal Dialysis; Salicylates

Topics: Analgesics; Analgesics, Non-Narcotic; Anti-Bacterial Agents; Antipyretics; Arsenic; Bismuth; Cadmium; Carbon Tetrachloride Poisoning; Contrast Media; Glycols; Gold; Heat Exhaustion; Insecticides; Kidney Diseases; Lead Poisoning; Mercury Poisoning; Metals; Poisoning; Radiation Injuries; Salicylates; Sulfonamides; Toxicology; Uranium; Venoms

The profile of urinary salicylate metabolites was determined after an i.p. administration of acetylsalicylic acid (ASA) to CCl4-cirrhotic rats to rats which in addition to CCl4 received an oral dose of silymarin throughout the CCl4 treatment to produce cirrhosis and to control groups. ASA esterase activity was determined in serum and livers. The time course of plasma concentration of salicylates in similar groups was followed after the i.p. injection of ASA. The cirrhotic animals showed a lack of urinary glucuronides and an increase in urinary gentisic and salicylic acids. The activities of plasma and serum ASA esterase were significantly increased in cirrhosis and the plasma half-life of ASA was reduced. The simultaneous administration of silymarin (50 mg/kg of b.w.) along with CCl4, completely prevented all the alterations. The mechanism by which silymarin prevented those alterations is not completely known but our results establish the potential use of silymarin in cirrhotic patients to prevent disorders in drug metabolism and disposition frequently found in patients with liver diseases.

Topics: Animals; Aspirin; Carbon Tetrachloride Poisoning; Carboxylic Ester Hydrolases; Flavonoids; Liver; Liver Cirrhosis, Experimental; Male; Rats; Rats, Inbred Strains; Salicylates; Silymarin

The profile of urinary salicylate metabolites was determined after an oral administration of acetylsalicylic acid (ASA) to: 1, control rats; 2, rats treated with CCl4 and 3, rats intoxicated with CCl4 and also pretreated with colchicine for 7 days. The following enzymatic activities were determined: liver and plasma ASA-esterase, liver UDP-glucuronyltransferase and liver aniline hydroxylase. The time course of plasma concentration of salicylates in similar groups were followed after the intraperitoneal administration of acetylsalicylic acid (ASA), salicylic acid (SA) or gentisic acid (GA). The animals acutely intoxicated with CCl4 showed a reduction in urinary excretion of glucuronates and an increased urinary excretion of gentisic and salicylic acids. The activities of plasma and liver ASA-esterases were significantly increased in CCl4-treated rats while the aniline hydroxylase was reduced and the UDP-glucuronyltransferase remained unchanged. The plasma half lives of salicylates were reduced in CCl4-treated rats regardless of the administered parent compound. Colchicine pre-treatment completely prevented the alterations produced by acute intoxication with CCl4. The heterogeneity of liver metabolic dysfunctions present in acute liver damage was evidenced. It is emphasized that the pharmacokinetic alterations produced by acute liver injury can be the result of complex factors that may involve changes in circulation, hepatic binding protein and other routes of elimination.

Topics: Animals; Aspirin; Carbon Tetrachloride Poisoning; Gentisates; Half-Life; Liver; Male; Rats; Rats, Inbred Strains; Salicylates

A recent clinical advance has been the discovery that many drug-induced hepatic diseases result from the metabolic activation of chemically stable drugs to potent alkylating agents by the liver. In addition to the liver, however, the kidney also contains active enzyme systems capable of metabolically activating drugs and other chemicals. For this reason a systematic investigation of the possible role of metabolic activation in the pathogenesis of several drug-induced renal diseases has been undertaken. These laboratory results are reviewed in the light of the clinical spectrum of the renal injuries, and possible therapeutic implications of these new findings are briefly discussed. The potential use of these models of nephrotoxicity to probe a variety of physiologic and pathophysiologic mechanisms of renal function are noted.

Topics: Acetaminophen; Analgesics; Animals; Carbon Tetrachloride Poisoning; Cephaloridine; Chloroform; Cytochrome P-450 Enzyme System; Disease Models, Animal; Dose-Response Relationship, Drug; Furans; Furosemide; Glutathione; Humans; Kidney; Kidney Diseases; Kidney Tubular Necrosis, Acute; Kidney Tubules, Proximal; Protein Binding; Salicylates; Toxicology

Topics: Aspirin; Carbon Tetrachloride; Carbon Tetrachloride Poisoning; Iron; Salicylates