Year:
2007
Abstract Number:
0899-P
The Mitochondria Toxicity of Antihyperlipidemic Agents Bezafibrate and Fenofibrate Recent epidemiological studies Recent epidemiological studies concerning with lipid intervention trials such as FIELD and BIP studies indicated that antihyperlipidemic agents, fibrates, protect from the onset of type2 diabetes. However, long-term teatment with antihyperlipidemic agents may occur mitochondria (MT) toxicity. Therefore, MT toxicity of antihyperlipidemic agent bezafibrate (BF) was compared with that of fenofibrate (FF), using freshly isolated rat liver MT. FF is known to inhibit strongly the electron transport at complex I in the respiratory chain, but the knowledge on the uncoupling effect on the oxidative phosphorylation is not available. In the present study, the MT toxicity of BF was compared with that of FF with regard to the inhibitiory effect on electron transport system and the uncoupling effect on the oxidative phosphorylation. Rat liver MT were prepared by the usual methods and the respiration was measured by means of oxygen electrode (Iijima Electronics Co. LTD). The effects of BF and FF on H+-ATPase (latent ATPase) and 2,4-dinitrophenol (DNP)-enhanced ATPase (DNP-ATPase) were studied by assaying inorganic phosphate enzymatically released from ATP for detecting both uncoupling effect and inhibitory effect on the energy transfer system.
BF inhibited the NAD-linked electron transport at complex I at significantly higher concentrations than FF, and did not interfere with the succinate-linked respiratory chain. Freshly prepared MT showed no ATPase activity, and the ATPase activity was enhanced by both BF and FF in a dose-dependent manner. These were indicated that the uncoupling effect and the enhancing effect of BF were significantly lower than those of FF. DNP-ATPase was not inhibited by both BF and FF at all, indicating no inhibitory effect on the energy transfer system. From these results, it was concluded that BF as well as FF showed MT toxicity by both fashions of uncoupling effect and electron transport inhibition at complex I. Finally, BF was markedly weaker than FF in the both toxic reactions, suggesting that BF is significantly less toxic than FF in vivo. KOUJI YAMADA, KASUMI TSUNODA, MIO HIRATUKA, KIYOSHI KAWAI, KAZUO KAJITA, TATSUO ISHIZUKA, Gifu, Japan, Ohbu, Japan 0899-P Diabetic Dyslipidemia
BF inhibited the NAD-linked electron transport at complex I at significantly higher concentrations than FF, and did not interfere with the succinate-linked respiratory chain. Freshly prepared MT showed no ATPase activity, and the ATPase activity was enhanced by both BF and FF in a dose-dependent manner. These were indicated that the uncoupling effect and the enhancing effect of BF were significantly lower than those of FF. DNP-ATPase was not inhibited by both BF and FF at all, indicating no inhibitory effect on the energy transfer system. From these results, it was concluded that BF as well as FF showed MT toxicity by both fashions of uncoupling effect and electron transport inhibition at complex I. Finally, BF was markedly weaker than FF in the both toxic reactions, suggesting that BF is significantly less toxic than FF in vivo. KOUJI YAMADA, KASUMI TSUNODA, MIO HIRATUKA, KIYOSHI KAWAI, KAZUO KAJITA, TATSUO ISHIZUKA, Gifu, Japan, Ohbu, Japan 0899-P Diabetic Dyslipidemia
Congress:
67th Scientific Sessions (2007)
Category:
Diabetic Dyslipidemia