Protective effect of ursodeoxycholic acid on liver mitochondrial function in rats with alloxan-induced diabetes: link with oxidative stress.
We investigated the effects of ursodeoxycholic acid (UDCA) on mitochondrial functions and oxidative stress and evaluated their relationships in the livers of rats with alloxan-induced diabetes. Diabetes was induced in male Wistar rats by a single alloxan injection (150 mg kg(-1) b.w., i.p.). UDCA (40 mg kg(-1) b.w., i.g., 30 days) was administered from the 5th day after the alloxan treatment. Mitochondrial functions were evaluated by oxygen consumption with Clark oxygen electrode using succinate, pyruvate+malate or palmitoyl carnitine as substrates and by determination of succinate dehydrogenase and NADH dehydrogenase activities. Liver mitochondria were used to measure chemiluminiscence enhanced by luminol and lucigenin, reduced liver glutathione and the end-products of lipid peroxidation. The activities of both NADH dehydrogenase and succinate dehydrogenase as well as the respiratory control (RC) value with all the substrates and the ADP/O ratio with pyruvate+malate and succinate as substrates were significantly decreased in diabetic rats. UDCA developed the beneficial effect on the mitochondrial respiration and oxidative phosphorylation parameters in alloxan-treated rats, whereas the activities of mitochondrial enzymes were increased insignificantly after the administration of UDCA. The contents of polar carbonyls and MDA as well as the chemiluminescence with luminol were elevated in liver mitochondria of diabetic rats. The treatment with UDCA normalized all the above parameters measured except the MDA content. UDCA administration prevents mitochondrial dysfunction in rats treated with alloxan and this process is closely connected with inhibition of oxidative stress by this compound.
Lukivskaya
Oxana
O
Department of Experimental Hepatology, Institute of Biochemistry, National Academy of Sciences, BLK-50, Grodno, Belarus.
Patsenker
Eleonora
E
Buko
Vyacheslav U
VU
D000496:Alloxan; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D008099:Liver / Q000503:physiopathology*; D008163:Luminescent Measurements; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D009245:NADH Dehydrogenase / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013385:Succinate Dehydrogenase / Q000378:metabolism; D014580:Ursodeoxycholic Acid / Q000494:pharmacology* / Q000627:therapeutic use
D008315:Malondialdehyde; D000496:Alloxan; D014580:Ursodeoxycholic Acid; D013385:Succinate Dehydrogenase; D009245:NADH Dehydrogenase