Diabetes and hypertriglyceridemia modify the mode of acetaminophen-induced hepatotoxicity and nephrotoxicity in rats and mice.
Certain disease conditions can modify drug-induced toxicities, which, in turn, may cause a medication-related health crisis. Therefore, preclinical investigations into the alterations in drug-induced toxicities using appropriate disease animal models are very important. This paper reviews the reported data related to the effects of diabetes and hypertriglyceridemia, common lifestyle-related diseases in a modern society, on acetaminophen (APAP)-induced hepatotoxicity and nephrotoxicity in rats and mice. It has generally been reported that diabetes protects rats and mice from APAP-induced hepatotoxicity and there are several reports that help to speculate on the effects of diabetes on APAP-induced nephrotoxicity. In fructose-induced hypertriglyceridemic rats, hepatotoxicity of APAP becomes apparently less severe, whereas nephrotoxicity of APAP becomes significantly more severe. The mechanisms of alteration of APAP-induced hepatorenal toxicity under diabetic and hypertriglyceridemic conditions are also discussed in this paper.
Doi
Kunio
K
Nippon Institute for Biological Science, Shin-Machi, Ome, Tokyo 198-0024, Japan. kunio-doi@nibs.or.jp
Ishida
Katsuhiko
K
D000082:Acetaminophen / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity*; D018712:Analgesics, Non-Narcotic / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D003920:Diabetes Mellitus / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D006801:Humans; D015228:Hypertriglyceridemia / Q000378:metabolism* / Q000503:physiopathology; D008658:Inactivation, Metabolic / Q000502:physiology; D007674:Kidney Diseases / Q000139:chemically induced*; D051379:Mice; D051381:Rats
D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen