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Mitochondrial reactive oxygen species (ROS) cause kidney damage in diabetes. We investigated the source and site of ROS production by kidney cortical tubule mitochondria in streptozotocin-induced type 1 diabetes in rats. In diabetic mitochondria, the increased amounts and activities of selective fatty acid oxidation enzymes is associated with increased oxidative phosphorylation and net ROS production with fatty acid substrates (by 40% and 30%, respectively), whereas pyruvate oxidation is decreased and pyruvate-supported ROS production is unchanged. Oxidation of substrates that donate electrons at specific sites in the electron transport chain (ETC) is unchanged. The increased maximal production of ROS with fatty acid oxidation is not affected by limiting the electron flow from complex I into complex HI. The maximal capacity of the ubiquinol oxidation site in complex HI in generating ROS does not differ between the control and diabetic mitochondria. In conclusion, the mitochondrial ETC is neither the target nor the site of ROS production in kidney tubule mitochondria in short-term diabetes. Mitochondrial fatty acid oxidation is the source of the increased net ROS production, and the site of electron leakage is located proximal to coenzyme Q at the electron transfer flavoprotein that shuttles electrons from acyl-CoA dehydrogenases to coenzyme Q. Diabetes 61:2074-2083, 2012, Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) (1). Hyperlipidemia is an independent factor in renal injury in animals (2) and humans (3). Increased fatty acid [...]

OBJECTIVE--Haptoglobin (Hp) binds free Hb, inhibiting Hb-induced oxidative damage. As oxidative stress has been associated with microvascular complications, we evaluated the relationship between Hp genotype and microalbuminuria, macroalbuminuria, end-stage renal disease (ESRD), and early renal function decline in type 1 diabetes. RESEARCH DESIGN AND METHODS--Participants from the Epidemiology of Diabetes Complications Study with DNA available were studied for the incidence of microalbuminuria (albumin excretion rate [AER] 20-200 µg/min), macroalbuminuria (AER >200 µg/min), ESRD (renal dialysis or transplantation), and renal function decline (a decline ≥ 30 ml/min per 1.73 [m.sup.2] from baseline estimated [by the Cockcroft-Gault equation] glomerular filtration rate [eGFR] in those with baseline eGFR >60 ml/min per 1.73 [m.sup.2]). RESULTS--The proportions with the Hp 2/2, 2/1, and 1/1 genotype were 43.4, 44.4, and 12.1%, respectively. During 18 years of follow-up, the incidence of eGFR decline, microalbuminuria, macroalbuminuria, and ESRD was 42.0, 40.5, 16.7, and 12.2%, respectively. No significant univariate differences were observed by Hp genotype. However, in multivariable Cox models, an ~twofold increased risk was observed for the Hp 2/2 compared with the Hp 1/1 genotype for eGFR decline (hazard ratio 1.79 [95% CI 1.06-3.00]) and ESRD (2.74 [1.17-6.45]); no significant associations were observed for microalbuminuria or macroalbuminuria. CONCLUSIONS--These data suggest that although Hp genotype is not associated with albuminuria per se, it may be an independent determinant of early renal function decline and progression to ESRD. Understanding these apparent contradictory findings may provide further insight into the pathogenesis of renal disease in type 1 diabetes., Reactive oxygen species have been implicated in both the etiology and progression of diabetes complications, including nephropathy (1). However, clinical trials assessing the impact of antioxidant supplementation on micro- and [...]

GAMBLERS DON'T LEARN FROM THEIR MISTAKES THE STUDY 'Executive Function Abnormalities in Pathological Gamblers,' Clinical Practice and Epidemiology in Mental Health, March 2008 THE FINDINGS A trip through Las Vegas [...]

Byline: Daniela. Domanico, Serena. Fragiotta, Alessandro. Cutini, Carmela. Carnevale, Luigi. Zompatori, Enzo. Vingolo Aims: The aim was to evaluate circulating levels of reactive oxygen species (ROS) and changes in central [...]

Byline: Renu. Dayal, Amrita. Singh, Anubhuti. Pandey, Kaushala. Mishra In normal functioning of the cell, there is a balance between generation and neutralization of reactive oxygen species (ROS) by endogenous [...]

According to the authors of recent research from New York City, New York, 'Problem To evaluate associations between hyperuricemia and increases in production of reactive oxygen species (ROS) and tumor [...]