Effect of clofibrate on plasma lipid concentration and liver malic enzyme gene expression in rats with experimental chronic renal failure.
Fibrates have been used clinically to treat dyslipidemias, including chronic renal failure (CRF)-related hypertriacylgliceridemia. In addition to their effects on plasma triacylglycerol concentration, fibrates also induce hepatomegaly (due to peroxisome proliferation) and increase liver malic enzyme activity. Since most experiments regarding fibrates action have been performed on healthy animals, in this paper we compare the effect of clofibrate on: a) plasma lipid concentration; b) liver weight; c) liver malic enzyme gene expression (malic enzyme activity, malic enzyme protein level and malic enzyme mRNA abundance) in control (sham-operated) animals and rats with CRF. The data presented in this paper indicate that: a) the clofibrate treatment causes a decrease in triacylglycerol concentration both in the control and rats with CRF, however the effect of the drug was more pronounced in the latter; b) administration of clofibrate induces hepatomegaly both in the control and rats with CRF; c) the liver malic enzyme gene expression is similarly affected by clofibrate in the control and rats with CRF. It is concluded that the beneficial, therapeutic effect of clofibrate on plasma lipid concentration is more pronounced in rats with CRF, but the side effects (hepatomegaly and the increase in malic enzyme gene expression) of fibrates are essentially similar in the control and rats with CRF.
Korczyńska
J
J
Department of Biochemistry, Medical University of Gdańsk, Poland.
Stelmańska
E
E
Nieweglowski
T
T
Szołkiewicz
M
M
Rutkowski
B
B
Swierczyński
J
J
D000818:Animals; D001806:Blood Urea Nitrogen; D015153:Blotting, Western; D002784:Cholesterol / Q000097:blood; D002994:Clofibrate / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000378:metabolism*; D008055:Lipids / Q000097:blood*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008291:Malate Dehydrogenase / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D015347:RNA Probes; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood
D000960:Hypolipidemic Agents; D008055:Lipids; D015347:RNA Probes; D014280:Triglycerides; D012313:RNA; D002784:Cholesterol; D008291:Malate Dehydrogenase; C034544:D-malate dehydrogenase (decarboxylating); D002994:Clofibrate