Examination of the protective effect of ICRF-187 and dimethyl sulfoxide against acetaminophen-induced hepatotoxicity in Syrian golden hamsters.
The protective activity of 1,2-bis(3,5-dioxopiperazin-l-yl)propane (ICRF-187) and dimethyl sulfoxide (DMSO) was tested against acetaminophen-induced hepatotoxicity. Male Syrian golden hamsters injected intraperitoneally between 18:00 h and 20:00 h for 2 consecutive days with acetaminophen (N-acetyl-p-aminophenol) (300 mg/kg) displayed signs of hepatotoxicity as evidenced by increases in enzyme activity and cellular damage. Forty-eight hours after the second acetaminophen dose, the activities of serum glutamic-pyruvic transaminase and alkaline phosphatase were increased compared with levels found in hamsters given only saline. In addition, hepatocellular necrosis was evident in acetaminophen-treated animals. ICRF-187 (300 mg/kg) given 1 h before acetaminophen attenuated the increases in enzyme activities, and both DMSO (7.3 g/kg) and ICRF-187 reduced the incidence and severity of acetaminophen-induced hepatocellular injury. Both ICRF-187 and DMSO are capable of altering free radical-mediated toxicity in other experimental systems. Whether these compounds reduce acetaminophen-induced liver toxicity by a similar mechanism remains to be determined.
D000082:Acetaminophen / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury; D006224:Cricetinae; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D008107:Liver Diseases / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008647:Mesocricetus; D009336:Necrosis / Q000139:chemically induced; D010879:Piperazines / Q000494:pharmacology*; D011929:Razoxane / Q000494:pharmacology*
D001798:Blood Proteins; D010879:Piperazines; D000082:Acetaminophen; D011929:Razoxane; D000410:Alanine Transaminase; D004121:Dimethyl Sulfoxide