Corte Cristiane L Dalla, Fachinetto Roselei, Puntel Robson, Wagner Caroline, Nogueira Cristina W, Soares Félix A Antunes, Rocha João B T
Federal University of Santa Maria, Center of Exacts and Natural Sciences, Chemistry Department, Graduation Program of Toxicological Biochemistry, Santa Maria, RS, Brazil.
Basic Clin Pharmacol Toxicol. 2009 Jul;105(1):51-7. doi: 10.1111/j.1742-7843.2009.00417.x. Epub 2009 Apr 16.
The aim of this study was to assess the toxic effects of chronic exposure to fluphenazine in liver and kidney of rats, as well as the possible protective effect of diphenyl diselenide on the fluphenazine-induced damage. Long-term treatment with fluphenazine caused an increase in lipid peroxidation levels in liver and kidney homogenates. Diphenyl diselenide treatment did not affect delta-aminolevulinate dehydratase (delta-ALA-D) activity, but fluphenazine alone or in combination with diphenyl diselenide showed an inhibitory effect on delta-ALA-D activity in liver. Diphenyl diselenide plus fluphenazine treatment increased the reactivation index of hepatic delta-ALA-D by approximately 80%. Superoxide dismutase activity decreased in liver of rats treated with fluphenazine alone. The combined treatment with fluphenazine and diphenyl diselenide was able to ameliorate superoxide dismutase activity in liver of rats. Catalase activity was augmented in liver from rats treated with fluphenazine, and this increase was prevented when diphenyl diselenide was co-administered. Taken together, these results indicate that the association of diphenyl diselenide with fluphenazine could protect the liver from lipid peroxidation and ameliorate superoxide dismutase and catalase activities. Moreover, our data point to the relationship between the oxidative stress and fluphenazine treatment in liver and kidney of rats.
本研究的目的是评估大鼠长期接触氟奋乃静对肝脏和肾脏的毒性作用，以及二苯基二硒醚对氟奋乃静诱导损伤的可能保护作用。长期用氟奋乃静治疗导致肝脏和肾脏匀浆中脂质过氧化水平升高。二苯基二硒醚处理不影响δ-氨基乙酰丙酸脱水酶（δ-ALA-D）活性，但单独使用氟奋乃静或与二苯基二硒醚联合使用均对肝脏中的δ-ALA-D活性有抑制作用。二苯基二硒醚加氟奋乃静治疗使肝脏δ-ALA-D的再激活指数提高了约80%。单独用氟奋乃静治疗的大鼠肝脏中超氧化物歧化酶活性降低。氟奋乃静与二苯基二硒醚联合治疗能够改善大鼠肝脏中的超氧化物歧化酶活性。用氟奋乃静治疗的大鼠肝脏中过氧化氢酶活性增强，而当同时给予二苯基二硒醚时，这种增加被阻止。综上所述，这些结果表明二苯基二硒醚与氟奋乃静联合使用可保护肝脏免受脂质过氧化，并改善超氧化物歧化酶和过氧化氢酶活性。此外，我们的数据表明大鼠肝脏和肾脏中氧化应激与氟奋乃静治疗之间的关系。
