Promotion of the Toxic Action of Cyclophosphamide by Digestive Tract Luminal Ammonia in Rats

Overview

Journal ISRN Toxicol

Specialty Pharmacology

Date 2013 Jun 1

PMID 23724282

Citations 1

Authors

Jury Ju Ivnitsky

Timur V Schafer

Vladimir L Rejniuk

Affiliations

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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.

Citing Articles

Secondary Dysfunction of the Intestinal Barrier in the Pathogenesis of Complications of Acute Poisoning.

Ivnitsky J, Schafer T, Rejniuk V, Vakunenkova O J Evol Biochem Physiol. 2022; 58(4):1075-1098.

PMID: 36061072 PMC: 9420239. DOI: 10.1134/S0022093022040123.

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