Drug Metabolism and Pharmacokinetics
Print ISSN : 0916-1139
Drugs and Hepatic Peroxisome Proliferation
[in Japanese]
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JOURNAL FREE ACCESS

1986 Volume 1 Issue 2 Pages 179-189

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Abstract
The peroxisome is an intracellular granule characterized by the presence of catalase, carnitine acetyltransferase and several hydrogen peroxide-generating enzymes, including the enzyme system involved in the β-oxidation of long-chain fatty acids. Clofibrate, as well as other potent hypolipidemic agents, causes massive hepatomegaly when administered to rodents, chickens and other species. This hepatomegaly is characteristically associated with a marked increase in the number and volume densities of peroxisomes in the liver. Furthermore, several studies have now established that certain chemicals (hypolipidemic peroxisome proliferators) induce hepatocellular carcinoma in both mice and rats. However, whether there is a direct interrelationship between the drug action, peroxisome proliferation and carcinoem genecity is yet to be established. In this revi, I have summarized recent publications concerning the effects of many chemicals on the characteristics of hepatic peroxisomes. The effects of these chemicals on peroxisomes (number, size and emzyme composition) are species-, sex-, and dose-depend. For example, clofibrate, nafenopin, Wy-14, 643, DEHP, etc induced hepatic peroxisome proliferation in the rodeuts. However, any damage of the liver and hepatic poroxisome proliferation in the human freintest with clofibrate or fenofibrate, were not found. On the other hand it is impotant finding for developing a new drug that certain hypolipidemic peroxisome proliferators induce hepatocarcinoma in rodents. However the species difference of the effect on hepatic peroxisomes is extremely marked, and also there is no report concernimg hepatocarcinogenesis by these drugs in human and other primates. As seen in this review, althongh there are many works concerning peroxisome protiferation, serum lipids level, hepatotoxicity, the interrelationship of these phenomena has not yet been elucidated. Then to understand the meanings of the changes in hepatic peroxisomes, it is essential for taking a new turn of the meanings of the changes in hepatic peroxisomes to analyze in detail many data for the mode of action, species difference and sexdiffernce of the effect of these drugs including the drugs other than hypolipidemic peroxisome proliferator.
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© The Japanese Society for the Study of Xenobiotics
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