Reactive oxygen species generation is modulated by mitochondrial kinases: correlation with mitochondrial antioxidant peroxidases in rat tissues.

Mitochondrial hexokinase (mt-HK) and creatine kinase (mt-CK) activities have been recently proposed to reduce the rate of mitochondrial ROS generation through an ADP re-cycling mechanism. Here, we determined the role of mt-HK and mt-CK activities in regulate mitochondrial ROS generation in rat brain, kidney, heart and liver, relating them to the levels of classical antioxidant enzymes. The activities of both kinases were significantly higher in the brain than in other tissues, whereas the activities of catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) were higher in both liver and kidney mitochondria. In contrast, manganese superoxide dismutase (Mn-SOD) activity was not significantly different among these tissues. Activation of mitochondrial kinases by addition of their substrates increased the ADP re-cycling and thus the respiration by enhancing the oxidative phosphorylation. Succinate induced hydrogen peroxide (H(2)O(2)) generation was higher in brain than in kidney and heart mitochondria, and the lowest in liver mitochondria. Mitochondrial membrane potential (DeltaPsi(m)) and H(2)O(2) production, decreased with additions of 2-DOG or Cr to respiring brain and kidney mitochondria but not to liver. The inhibition of H(2)O(2) production by 2-DOG and Cr correspond to almost 100% in rat brain and about 70% in kidney mitochondria. Together our data suggest that mitochondrial kinases activities are potent preventive antioxidant mechanism in mitochondria with low peroxidase activities, complementing the classical antioxidant enzymes against oxidative stress.

Nandrolone decanoate impairs exercise-induced cardioprotection: role of antioxidant enzymes.

The beneficial effects of exercise in reducing the incidence of cardiovascular diseases are well known and the abuse of anabolic androgenic steroids (AAS) has been associated to cardiovascular disorders. Previous studies showed that heart protection to ischemic events would be mediated by increasing the antioxidant enzyme activities. Here, we investigated the impact of exercise and high doses of the AAS nandrolone decanoate (DECA), 10 mgkg(-1) body weight during 8 weeks, in cardiac tolerance to ischemic events as well as on the activity of antioxidant enzymes in rats. After a global ischemic event, hearts of control trained (CT) group recovered about 70% of left ventricular developed pressure, whereas DECA trained (DT), control sedentary (CS) and DECA sedentary (DS) animals recovered only about 20%. Similarly, heart infarct size was significantly lower in the CT group compared to animals of the three other groups. The activities of the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) were significantly higher in CT animals than in the other three groups, whereas catalase activity was not affected in any group. Together, these results indicate that chronic treatment with DECA cause an impairment of exercise induction of antioxidant enzyme activities, leading to a reduced cardioprotection upon ischemic events.