Nikolić-Kokić Aleksandra, Mijušković Ana, Tatalović Nikola, Nestorov Jelena, Miler Marko, Oreščanin-Dušić Zorana, Nikolić Milan, Milošević Verica, Blagojević Duško, Spasić Mihajlo, Miljević Čedo
a Department of Physiology , Institute for Biological Research "Siniša Stanković," University of Belgrade , Belgrade , Serbia.
b Department of Biochemistry , Institute for Biological Research "Siniša Stanković," University of Belgrade , Belgrade , Serbia.
J Toxicol Environ Health A. 2016;79(20):905-11. doi: 10.1080/15287394.2016.1201706.
The use of atypical antipsychotic drugs (APD) was reported to be associated with adverse effects on the kidneys. Thus, the aim of this study was to examine whether APD exerted their adverse effects by interfering with the renal antioxidant defense system. Male 3-mo-old Wistar rats were treated for 28 d with ziprasidone (ZIP), clozapine (CLO), or sertindole (SER) using a daily dose recommended for antipsychotic drug therapy. The expression and activities of antioxidant enzymes superoxide dismutase (SOD) type 1 and type 2, catalase (CAT), glutathione reductase (GR), and glutathione S-transferases (GSTs) activity were measured in the kidneys. Changes in the kidneys were also evaluated histologically. Ziprasidone, CLO, and SER reduced renal SOD type 1 and type 2 activities. Decreased CAT activity was observed only in SER-treated rats. An inhibition in GR activity and increased activity of GST was found only after treatment with CLO. Histological analysis showed dilatation of proximal tubules in kidneys with all three drugs. In conclusion, data indicate that redox disturbances may contribute to renal morphologic alterations in proximal tubules in rats treated with all APD.
据报道，使用非典型抗精神病药物（APD）会对肾脏产生不良影响。因此，本研究的目的是检查APD是否通过干扰肾脏抗氧化防御系统而发挥其不良影响。使用抗精神病药物治疗推荐的日剂量，对3月龄雄性Wistar大鼠用齐拉西酮（ZIP）、氯氮平（CLO）或舍吲哚（SER）治疗28天。测量肾脏中抗氧化酶1型和2型超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽还原酶（GR）的表达和活性以及谷胱甘肽S-转移酶（GSTs）的活性。还对肾脏的变化进行了组织学评估。齐拉西酮、CLO和SER降低了1型和2型肾脏SOD的活性。仅在SER治疗的大鼠中观察到CAT活性降低。仅在CLO治疗后发现GR活性受到抑制且GST活性增加。组织学分析显示，使用这三种药物后肾脏近端小管均有扩张。总之，数据表明氧化还原紊乱可能导致所有APD治疗的大鼠近端小管出现肾脏形态学改变。
