Comparison of the susceptibility of hepatocytes from postnatal and adult mice to hepatotoxins.
Age-related changes of susceptibility to hepatotoxicity induced by four hepatotoxic compounds were investigated using an isolated mouse hepatocyte model. Hepatocytes isolated from 2-week-old mice and adult mice (8-10 weeks old) were exposed to different concentrations (including toxic concentrations) of paracetamol, furosemide, iodoacetic acid and t-butylhydroperoxide for incubation times up to 24 hr. Cell damage was assessed by leakage of lactate dehydrogenase. Analysis of variance indicated that the hepatocytes from the 2-week-old mice were less susceptible to the toxic effects of all four hepatotoxins. The activities of catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase were determined in both hepatocytes and whole liver from the two age groups. While catalase was significantly greater in adults, glutathione peroxidase, glutathione reductase and superoxide dismutase were all higher in the 2-week-old mice. Since these three enzymes are involved with protection against oxidative stress, it is likely that the higher activity in hepatocytes from 2-week-old mice is responsible for the reduced susceptibility to damage induced by the four hepatotoxins.
Adamson
G M
GM
Department of Pharmacology, University of Western Australia, Nedlands.
Harman
A W
AW
D000082:Acetaminophen / Q000633:toxicity*; D000375:Aging; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D002374:Catalase / Q000378:metabolism; D005665:Furosemide / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D007461:Iodoacetates / Q000633:toxicity*; D019807:Iodoacetic Acid; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D010545:Peroxides / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D020122:tert-Butylhydroperoxide
D007461:Iodoacetates; D010545:Peroxides; D000082:Acetaminophen; D005665:Furosemide; D020122:tert-Butylhydroperoxide; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005978:Glutathione; D019807:Iodoacetic Acid