Promotion of the Toxic Action of Cyclophosphamide by Digestive Tract Luminal Ammonia in Rats. (14th July 2011)

• Record Type: Journal Article
• Authors: Ivnitsky, Jury Ju.; Schäfer, Timur V.; Rejniuk, Vladimir L.
• Other Names: Chern C. L. Academic Editor.; Erikson K. M. Academic Editor.
• Is Part Of: ISRN toxicology. Volume 2011(2011)
• Publication Date: 2011-07-14
• Subjects: Toxicology -- Periodicals; Toxicology; Pharmacology; Toxicology; Pharmacology -- Periodicals; Toxicology -- Periodicals; Periodical; Periodicals; Fulltext; Internet Resources; Periodicals; 571.95
• DOI: 10.5402/2011/450875
• Languages: English
• ISSNs: 2090-6188

Abstract

Abstract : To estimate the influence of the digestive tract luminal ammonia pool on acute toxic effects of cyclophosphamide, the dynamics of blood ammonia, glutamine and urea level, symptoms of toxic action and the survival time have been studied in rats, intraperitoneally treated with cyclophosphamide, at the background of the gavage with non-lethal dose of ammonium acetate (12 mmol/kg, i.e., 0.35 LD50 ). Ammonium acetate enhanced the hyperammonaemic action of cyclophosphamide while promoting its lethal action: the mean survival time decreased 1.5, 2.1, 2.8, or 6.1 times at the background of cyclophosphamide i/p doses 200, 600, 1000, or 1400 mg/kg, respectively. Animals exposed to the combination of toxicants, manifested symptoms which were characteristic of the effect of lethal doses of ammonia salts. These data provide the evidence of the detrimental role of gastrointestinal luminal ammonia in the acute high-dose cyclophosphamide toxicity.