Table of Contents
ISRN Toxicology
Volume 2011, Article ID 450875, 4 pages
http://dx.doi.org/10.5402/2011/450875
Research Article

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

Laboratory of Origin, Institute of Toxicology, Federal Medical Biological Agency, 1, ul. Bekhtereva, St. Petersburg, 192019, Russia

Received 23 April 2011; Accepted 30 May 2011

Academic Editors: C. L. Chern and K. M. Erikson

Copyright © 2011 Jury Ju. Ivnitsky et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.