Aggravation of cyclophosphamide-induced acute neurological disorders under conditions of artificial acidification of chyme in rats.

The effect of artificial acidification of the intestinal content on neurological manifestations of acute severe cyclophosphamide intoxication was studied in rats. The animals were gavaged with 20 ml/kg sulfuric (0.05 M), hydrochloric, boric, or lactic acids (0.1 M) 3 h before intraperitoneal injections of the cytostatic in doses of 0, 200, 600, or 1000 mg/kg. The decrease in pH (by.0) and ammonia-producing activity of the cecal chyme developed within 3 h after administration of acids. Cyclophosphamide caused hyperammonemia; glutamine/ammonia and urea/ammonia ratios in the blood decreased. These changes augmented after administration of acids (boric acid produced maximum and lactic acid minimum effects). Acid treatment resulted in greatest elevation of ammonia level in the portal venous blood and a lesser elevation in the vena cava posterior blood. Acid treatment promoted manifestation of cyclophosphamide neurotoxic effect and animal death. Hence, acidification of the chyme inhibited the formation of ammonia in it, while ammonia release from the gastrointestinal tract into the blood increased; the treatment augmented hyperammonemia and aggravated the neurological manifestations of cyclophosphamide intoxication.

Effect of hypoxia on sodium and ammonium acetate toxicity for Daphnia.

Exposure of Daphnia in degassed (boiled) culturing water (hypoxia simulation) led to solitary lethal outcomes after more than 24 h. Before this term, hypoxia had no appreciable effect on the toxicity of sodium or ammonium acetate salts. The sensitivity of daphnias to the lethal effects of the tested chemicals did not change under conditions of normal oxygenation and increased sharply (by two orders of magnitude) under conditions of hypoxia, loosing the linear relationship with toxicant concentration. Ammonium acetate toxicity more markedly increased under conditions of hypoxia than sodium acetate toxicity. These data should be taken into consideration when predicting the results of combined effects of toxicants on water ecosystems and on human organism.

Increase of ammonia pool in the gastrointestinal tract of rats potentiates acute toxicity of cyclophosphamide.

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.