Background and purpose:The effects of hydrogen peroxide (H2O2) on uterine smooth muscle are not well studied. We have investigated the effect and the mechanism of action of exogenous hydrogen peroxide on rat uteri contractile activity [spontaneous and calcium ion (Ca 2+ )-induced] and the effect of such treatment on anti-oxidative enzyme activities. Experimental approach: Uteri were isolated from virgin Wistar rats and suspended in an organ bath. Uteri were allowed to contract spontaneously or in the presence of Ca 2+ (6 mM) and treated with H2O2 (2 mM-3 mM) over 2 h. Anti-oxidative enzyme activities (manganese superoxide dismutase-MnSOD, copper-zinc superoxide dismutase-CuZnSOD, catalase-CAT, glutathione peroxidase-GSHPx and glutathione reductase-GR) in H2O2-treated uteri were compared with those in uteri immediately frozen after isolation or undergoing spontaneous or Ca 2+ -induced contractions, without treatment with H2O2. The effect of inhibitors (propranolol, methylene blue, L-NAME, tetraethylamonium, glibenclamide and 4-aminopyridine) on H2O2-mediated relaxation was explored. Key results: H2O2 caused concentration-dependent relaxation of both spontaneous and Ca 2+ -induced uterine contractions. After H2O2 treatment, GSHPx and MnSOD activities were increased, while CuZnSOD and GR (In Ca 2+ -induced rat uteri) were decreased. N w -nitro-L-arginine methyl ester antagonized the effect of H2O2 on Ca 2+ -induced contractions. H2O2-induced relaxation was not affected by propranolol, potentiated by methylene blue and antagonized by tetraethylamonium, 4-aminopyridine and glibenclamide, with the last compound being the least effective. Conclusions and implications: H2O2 induced dose-dependent relaxation of isolated rat uteri mainly via changes in voltagedependent potassium channels. Decreasing generation of reactive oxygen species by stimulation of anti-oxidative pathways may lead to new approaches to the management of dysfunctional uteri.
The distribution of Copper-Zinc containing and Manganese-containing superoxide dismutase in the liver, kidney, interscapular brown adipose tissue (IBAT) and brain of the ground squirrel, as well as the effect of hibernation, was studied. Activity of both forms of SOD was highest in the liver and lowest in the brain. Activity of the Mn SOD in relation to total SOD was higher in the liver and kidney of the ground squirrel as compared with results reported for other rodents. The highest activity of Mn SOD in relation to total SOD was found in the IBAT and brain (36% and 49%, respectively). Total SOD activity per mg proteins and per g wet mass in IBAT and brain of hibernating animals was increased: for IBAT, p less than 0.05 and p less than 0.025, respectively; for brain, p less than 0.01 and p less than 0.025, respectively. Protein content in hibernating ground squirrel was not significantly changed. In the hibernating ground squirrel CuZn SOD activity in IBAT and brain was higher as compared with the active animal (p less than 0.025 and p less than 0.005, respectively). In the liver and kidney CuZn SOD was not significantly changed during the hibernation. In the liver and brain of the hibernating animals a lower Mn SOD activity was found (p less than 0.005 and p less than 0.05, respectively).
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