title: Increase of ammonia pool in the gastrointestinal tract of rats potentiates acute toxicity of cyclophosphamide.
abstract: For evaluation of the impact of changes of ammonia pool in the gastrointestinal tract on acute toxicity of cyclophosphamide, the dynamics of blood levels of ammonia and urea of rats was studied after intraperitoneal injection of cyclophosphamide (600 mg/kg) and clinical manifestations of intoxication and lifespan of rate were studied after cyclophosphamide injections in doses of 200, 600, 1000, and 1400 mg/kg alone or in combination with ammonium acetate. Ammonium acetate stimulated the hyperammoniemic and uremic effects of cyclophosphamide. Combined effects of the toxicants were associated with symptoms characteristic of acute poisoning with ammonium salts; these symptoms were not observed under the effect of ammonium acetate alone. Ammonium acetate stimulated the lethal effect of cyclophosphamide injected in doses of 200, 600, 1000, or 1400 mg/kg: the mean lifespan of rats decreased by 1.5, 2.1, 2.8, or 6.1 times, respectively. These data indicate that ammonia redistribution from the gastrointestinal tract into circulating blood is one of the mechanisms of thanatogenesis in acute cyclophosphamide intoxication.
authors.affiliation: Institute of Toxicology, Federal Biomedical Agency of Russia, St. Petersburg, Russia. vladton@mail.ru
authors.forename: V L
authors.initials: VL
authors.lastname: Rejniuk
authors.forename: T V
authors.initials: TV
authors.lastname: Schaefer
authors.forename: Ju Ju
authors.initials: JJ
authors.lastname: Ivnitsky
mesh_terms: D000641:Ammonia / Q000097:blood*; D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification*; D003520:Cyclophosphamide / Q000633:toxicity*; D041981:Gastrointestinal Tract / Q000378:metabolism*; D051381:Rats
chemical_list: D000970:Antineoplastic Agents; D000641:Ammonia; D003520:Cyclophosphamide