An ultrastructural and biochemical study of the effects of a 5-lipoxygenase inhibitor on peroxisome proliferation in rat liver and kidney

Abstract

The present study was undertaken to assess the effects of a drug candidate on the morphological and biochemical changes associated with peroxisome proliferation in the liver and kidneys of CD®BR rats. Zileuton, (Abbott-64077), a benzothiophene N-hydroxyurea, is a 5-lipoxygenase inhibitor which has potential therapeutic uses for conditions such as rheumatoid arthritis. To date, several hypolipidemic drugs, certain plasticizers, and a number of unrelated compounds are known to induce peroxisome proliferation in animals. Peroxisomes (also referred to as microbodies) are single membrane-bound organelles found in most tissues, however, their occurrence in hepatocytes is greater than in any other cell type. In the kidneys, peroxisomes are predominantly located in the cortex.The prolonged proliferation of hepatocellular peroxisomes is of concern since chronic proliferation of peroxisomes has been associated with an increase in hepatic tumors in rodents. In general, peroxisome proliferation can be assessed by an increase in peroxisome number and an increase in fatty acid β-oxidation activity.