Ammonia redistribution from the gastrointestinal tract to general circulation after intraperitoneal injection of cyclophosphamide to rats.
Ammonia level in the blood increased within 3 h after intraperitoneal injection of cyclophosphamide in doses of 200, 600, and 1000 mg/kg: by 1.4, 1.8, and 2.5 times in the blood from v. portae, by 1.5, 2.1, and 3.3 times in the blood from v. cava caud. caudally to vv. renales orifice, and by 1.8, 2.7, and 4.2 times, respectively, in the same vein cranially to vv. hepaticae. A positive portocaval gradient of ammonia concentration was abolished. Blood concentrations of glutamine and urea increased less markedly than those of ammonia. Ammonia and glutamine accumulation in isotonic saline injected to animals intraperitoneally 2.5 h after cyclophosphamide was stimulated depending on the drug dose. Blood concentrations of cytolysis markers (lactate dehydrogenase and alanine and aspartate transaminases) increased. Ammonia, glutamine, and urea concentrations in the blood remained high 18 h after injection of cyclophosphamide, the glutamine/ammonia ratio increased. These data indicate that a single intraperitoneal injection of cyclophosphamide to rats in doses of 200-1000 mg/kg disorders detoxification and stimulates transperitoneal diffusion of ammonia from the digestive tract to the posterior vena cava basin with the development of hyperammoniemia.
Institute of Toxicology, Federal Biomedical Agency of Russia, St. Petersburg, Russia.
T V
TV
Schäfer
V L
VL
Rejniuk
Yu Yu
YY
Ivnitsky
D000410:Alanine Transaminase / Q000097:blood; D000641:Ammonia / Q000097:blood* / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D041981:Gastrointestinal Tract / Q000378:metabolism*; D005973:Glutamine / Q000097:blood; D022124:Hyperammonemia / Q000097:blood* / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D051381:Rats; D014508:Urea / Q000097:blood
D005973:Glutamine; D000641:Ammonia; D003520:Cyclophosphamide; D014508:Urea; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase