This study was designed to determine which enzyme activities were first impaired in mitochondria exposed to 2,2'-azobis-(2-amidinopropane) dihydrochloride (AAPH), a known radical initiator. EPR spin-trapping revealed generation of reactive oxygen species although malondialdehyde formation remained very low. With increasing AAPH concentrations, State-3 respiration was progressively depressed with unaltered ADP/O ratios. A top-down approach demonstrated that alterations were located at the phosphorylation level. As shown by inhibitor titrations, ATP/ADP translocase activity was unaffected in the range of AAPH concentrations used. In contrast, AAPH appeared to exert a deleterious effect at the level of F1F0-ATPase, comparable with dicyclohexylcarbodi-imide, which alters Fo proton channel. A comparison of ATP hydrolase activity in uncoupled and broken mitochondria reinforced this finding. In spite of its pro-oxidant properties, AAPH was shown to act as a dose-dependent inhibitor of cyclosporin-sensitive permeability transition initiated by Ca2+, probably as a consequence of its effect on F1F0-ATPase. Resveratrol, a potent antiperoxidant, completely failed to prevent the decrease in State-3 respiration caused by AAPH. The data suggest that AAPH, when used under mild conditions, acted as a radical initiator and was capable of damaging F1F0-ATPase, thereby slowing respiratory chain activity and reducing mitochondrial antioxidant defences.
Alterations of the postprandial (pp) triglyceride (TG) response might play an important role in the development of atherosclerosis-thrombosis in non-insulin-dependent diabetic (NIDDM) patients. (BMI 30.3 ± 2.7 kg/m 2 ), under fair glycemic control (Hb A1 c 7.6 ± 1.6%), had moderately elevated fasting TG 2.6 ± 1.1 mmol/L and normal LDL cholesterol (2.6 ± 1 mmol/L).As expected, BZ reduced fasting TG (P< < 0.01) but had no effect on total cholesterol (TC) levels. Fasting glycemia was improved from 11.9 ± 3.3 to 9.7 ± 3.4 mmol/L (P < 0.04). PP nitine concentration in the rat liver. P P
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