Effects of the hypolipidemic drug nafenopin on the zona fasciculata of the rat adrenal cortex: a correlated biochemical and stereological study.
The effects of Nafenopin, a hypolipidemic drug, on the zona fasciculata of the rat adrenal cortex were investigated by biochemical, stereological, and cytochemical methods. Chronic Nafenopin treatment (5 days) significantly lowered serum cholesterol level, while it did not alter blood corticosterone concentration and 11beta-hydroxylase activity of adrenocortical cells. Stereology showed a significant increase in the average volume of zona fasciculata cells, which was almost exclusively due to smooth endoplasmic reticulum (SER) proliferation. The volume of lipid compartment was significantly reduced, whereas the volume of diaminobenzidine (DAB)-positive bodies (peroxisomes) per cell displayed a marked increase. Cholesterol administration per os to the treated animals raised the serum cholesterol level and completely reversed the Nafenopin effects. One day of Nafenopin administration provoked a slight but significant lipid depletion in adrenocortical cells, while 3 days of continuous drug treatment induced an extreme lipid depletion and a moderate increase in the SER coupled with a significant decrease in the plasma concentration of corticosterone. Since microsomal fraction and catalase seem to be involved in the cholesterol metabolism and utilization, the hypothesis is advanced that the Nafenopin-elicited SER and peroxisome proliferation is a compensatory response enabling adrenocortical cells to maintain an adequate level of hormonal output.
D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002784:Cholesterol / Q000008:administration & dosage / Q000097:blood; D003345:Corticosterone / Q000097:blood; D004121:Dimethyl Sulfoxide / Q000008:administration & dosage; D006651:Histocytochemistry; D008297:Male; D008854:Microscopy, Electron; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009255:Nafenopin / Q000494:pharmacology*; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D011422:Propionates; D009255:Nafenopin; D002784:Cholesterol; D006899:Mixed Function Oxygenases; D003345:Corticosterone; D004121:Dimethyl Sulfoxide