title: Aggravation of cyclophosphamide-induced acute neurological disorders under conditions of artificial acidification of chyme in rats.
abstract: 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.
authors.affiliation: Institute of Toxicology, Federal Biomedical Agency of Russia, St. Petersburg, Russia.
authors.forename: T V
authors.initials: TV
authors.lastname: Schaefer
authors.forename: V L
authors.initials: VL
authors.lastname: Rejuniuk
authors.forename: V N
authors.initials: VN
authors.lastname: Malakhovsky
authors.forename: Ju Ju
authors.initials: JJ
authors.lastname: Ivnitsky
mesh_terms: D000208:Acute Disease; D000284:Administration, Oral; D000641:Ammonia / Q000097:blood; D000818:Animals; D001888:Boric Acids / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000633:toxicity*; D005750:Gastric Juice / Q000737:chemistry; D005753:Gastric Mucosa / Q000378:metabolism*; D005973:Glutamine / Q000097:blood; D006851:Hydrochloric Acid / Q000008:administration & dosage; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D022124:Hyperammonemia / Q000150:complications / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D019344:Lactic Acid / Q000008:administration & dosage; D008297:Male; D020258:Neurotoxicity Syndromes / Q000150:complications / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D051381:Rats; D013270:Stomach / Q000473:pathology; D013464:Sulfuric Acids / Q000008:administration & dosage; D015996:Survival Rate; D014508:Urea / Q000097:blood
chemical_list: D001888:Boric Acids; D013464:Sulfuric Acids; D005973:Glutamine; D019344:Lactic Acid; D000641:Ammonia; D003520:Cyclophosphamide; D014508:Urea; C033158:sulfuric acid; D006851:Hydrochloric Acid; C032688:boric acid