Pyruvate inhibits clofibrate-induced hepatic peroxisomal proliferation and free radical production in rats.
In an effort to identify the effects of the 3-carbon compound pyruvate on free radical production, we measured hepatic total peroxisomal beta-oxidation and catalase activity and the production of lipofuscin-like products in male Sprague-Dawley rats consuming an adequate diet supplemented with pyruvate, vitamin E, or the peroxisome proliferator and free radical enhancer clofibrate for 22 days (n = 5 in each group). Clofibrate feeding induced hepatomegaly, a fivefold increase in total peroxisomal beta-oxidation activity, and a threefold increase in hepatic lipofuscin-like products (P < .05). Pyruvate but not vitamin E inhibited the increase in liver size by 70% (P < .05). Both pyruvate and vitamin E completely inhibited clofibrate-induced increases in lipofuscin-like products (P < .05). Pyruvate but not clofibrate or vitamin E increased plasma concentrations of the nitric oxide metabolites nitrite and nitrate (P < .05). We conclude that with clofibrate-induced peroxisomal proliferation and free radical production, pyruvate will inhibit peroxisomal proliferation and free radical production, inhibit free radical-induced lipid peroxidation, and enhance metabolism of nitric oxide.
Stanko
R T
RT
Clinical Nutrition Research Unit, Montefiore University Hospital, Pittsburgh, PA.
Sekas
G
G
Isaacson
I A
IA
Clarke
M R
MR
Billiar
T R
TR
Paul
H S
HS
D000818:Animals; D001835:Body Weight; D002374:Catalase / Q000032:analysis; D002994:Clofibrate / Q000037:antagonists & inhibitors*; D004032:Diet; D004347:Drug Interactions; D005609:Free Radicals / Q000032:analysis; D008062:Lipofuscin / Q000032:analysis; D008099:Liver / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008830:Microbodies / Q000187:drug effects* / Q000502:physiology; D008854:Microscopy, Electron; D009929:Organ Size; D010084:Oxidation-Reduction; D011773:Pyruvates / Q000008:administration & dosage*; D019289:Pyruvic Acid; D051381:Rats; D017207:Rats, Sprague-Dawley; D014810:Vitamin E / Q000008:administration & dosage*
D005609:Free Radicals; D008062:Lipofuscin; D011773:Pyruvates; D014810:Vitamin E; D019289:Pyruvic Acid; D002374:Catalase; D002994:Clofibrate