Diabetes and hypertriglyceridemia modify the mode of acetaminophen-induced hepatotoxicity and nephrotoxicity in rats and mice

J Toxicol Sci. 2009 Feb;34(1):1-11. doi: 10.2131/jts.34.1.


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.

Publication types

  • Review

MeSH terms

  • Acetaminophen / antagonists & inhibitors
  • Acetaminophen / metabolism
  • Acetaminophen / toxicity*
  • Analgesics, Non-Narcotic / antagonists & inhibitors
  • Analgesics, Non-Narcotic / metabolism
  • Analgesics, Non-Narcotic / toxicity*
  • Animals
  • Chemical and Drug Induced Liver Injury*
  • Diabetes Mellitus / metabolism*
  • Diabetes Mellitus / physiopathology
  • Disease Models, Animal
  • Humans
  • Hypertriglyceridemia / metabolism*
  • Hypertriglyceridemia / physiopathology
  • Inactivation, Metabolic / physiology
  • Kidney Diseases / chemically induced*
  • Mice
  • Rats


  • Analgesics, Non-Narcotic
  • Acetaminophen