Contini María Del Carmen, Millen Néstor, González Marcela, Benmelej Adriana, Fabro Ana, Mahieu Stella
Facultad de Bioquímica y Ciencias Biológicas (FBCB), Universidad Nacional del Litoral (UNL), Santa Fe, Argentina
Facultad de Bioquímica y Ciencias Biológicas (FBCB), Universidad Nacional del Litoral (UNL), Santa Fe, Argentina.
Toxicol Ind Health. 2016 Aug;32(8):1515-1526. doi: 10.1177/0748233714566876. Epub 2015 Jan 29.
The aim of this work was to study whether the increase in antioxidant defenses associated with orchiectomy may account for the reduced susceptibility to aluminum (Al) in male kidney and also to examine whether the reduced antioxidant defenses are associated with androgen levels in orchiectomized (ORX) rats treated with testosterone propionate (TP). Rats were divided into nine groups, namely, intact males (without treatment, treated with sodium lactate, and treated with Al), sham males, ORX males (without treatment, treated with sodium lactate, treated with TP, treated with Al, and treated with TP and Al). Al groups were chronically treated with aluminum lactate for 12 weeks (0.575 mg Al/100 g of body weight, intraperitoneally, three times per week). We reported that ORX rats treated with Al had significantly less lipid peroxidation and an increased level of reduced glutathione (GSH) and GSH/oxidized glutathione ratio in the kidney when compared with intact and TP-treated ORX rats. The activity of superoxide dismutase, catalase, and glutathione peroxidase in ORX rats was much greater than in intact or TP-administered ORX rats. Castration reduced the glomerular alterations caused by Al as well as the number of necrotic tubular cells and nuclear abnormalities. However, we observed a slight alteration in brush border, dilation of proximal tubules, mononuclear infiltrates, and interstitial fibrosis. Castrated males treated with TP showed that this intervention cancels the protective effect of the ORX. This finding suggests that androgens contribute to the development of renal alterations and proteinuria in rats treated with Al. Our results showed that ORX rats are protected against the induction of oxidative stress by Al, but the morphological damage to the kidney tissue induced by the cation was only reduced. Male intact rats treated with Al had more severe glomerulosclerosis, tubular damage, and proteinuria than ORX rats.
这项工作的目的是研究与睾丸切除术相关的抗氧化防御增加是否可以解释雄性肾脏对铝（Al）敏感性的降低，同时研究在接受丙酸睾酮（TP）治疗的去势（ORX）大鼠中，抗氧化防御的降低是否与雄激素水平有关。大鼠被分为九组，即完整雄性大鼠（未治疗、用乳酸钠治疗、用Al治疗）、假手术雄性大鼠、ORX雄性大鼠（未治疗、用乳酸钠治疗、用TP治疗、用Al治疗、用TP和Al治疗）。Al组用乳酸铝进行为期12周的慢性治疗（0.575 mg Al/100 g体重，腹腔注射，每周三次）。我们报告称，与完整和TP治疗的ORX大鼠相比，用Al治疗的ORX大鼠肾脏中的脂质过氧化显著减少，还原型谷胱甘肽（GSH）水平和GSH/氧化型谷胱甘肽比值增加。ORX大鼠中超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶的活性远高于完整或TP给药的ORX大鼠。去势减少了由Al引起的肾小球改变以及坏死肾小管细胞的数量和核异常。然而，我们观察到刷状缘有轻微改变、近端小管扩张、单核细胞浸润和间质纤维化。用TP治疗的去势雄性大鼠表明，这种干预消除了ORX的保护作用。这一发现表明，雄激素有助于在用Al治疗的大鼠中肾脏改变和蛋白尿的发展。我们的结果表明，ORX大鼠对Al诱导的氧化应激具有保护作用，但阳离子对肾组织的形态学损伤仅有所减轻。用Al治疗的完整雄性大鼠比ORX大鼠有更严重的肾小球硬化、肾小管损伤和蛋白尿。
