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氯化亚锡对重铬酸钾诱导的大鼠肾毒性的保护作用:血红素加氧酶-1预先诱导的必要性及与某些抗氧化酶的无关性

Protective effect of SnCl2 on K2Cr2O7-induced nephrotoxicity in rats: the indispensability of HO-1 preinduction and lack of association with some antioxidant enzymes.

作者信息

Barrera Diana, Maldonado Perla D, Medina-Campos Omar N, Hernández-Pando Rogelio, Ibarra-Rubio María E, Pedraza-Chaverrí José

机构信息

Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, Edificio B, Segundo Piso, Lab 209, Ciudad Universitaria, 04510 México, DF, México.

出版信息

Life Sci. 2003 Oct 24;73(23):3027-41. doi: 10.1016/j.lfs.2003.06.002.

Abstract

We have shown that the ameliorative effect of stannous chloride (SnCl2) pretreatment on potassium dichromate (K2Cr2O7)-induced renal damage 24 h after K2Cr2O7 injection was associated with the induction of heme oxygenase-1 (HO-1). In this work we evaluated: (a) if the protective effect of SnCl2 (given 12 h before K2Cr2O7) is associated with changes in the renal activity of HO-1, superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), and catalase (CAT) 24 and 48 h after K2Cr2O7 injection, and (b) if HO-1 induction is indispensable before K2Cr2O7 injection. It was found that the protective effect of SnCl2 on renal function was observed both at 24 and 48 h reaching its maximum at 24 h when HO-1 expression was higher. Cu,Zn-SOD, Mn-SOD, and GR activities remained unchanged whereas GPx and CAT activities decreased at 48 h in K2Cr2O7-treated rats. The activity of Cu,Zn-SOD, Mn-SOD, GPx, CAT, and GR was unchanged in the SnCl2-treated rats. To fulfill the objective (b) groups of rats treated with K2Cr2O7 and SnCl2 (given at the same time or 12 h after K2Cr2O7) were studied 24 h after K2Cr2O7-injection. The simultaneous injections of SnCl2 and K2Cr2O7 had no protective effect whereas the injection of SnCl2 12 h after K2Cr2O7 exacerbated renal damage. In conclusion, the protective effect of SnCl2 on K2Cr2O7-induced nephrotoxicity is associated with HO-1 induction and not with other antioxidant enzymes (Cu,Zn-SOD, Mn-SOD, GPx, GR, and CAT) and SnCl2 has a preventive and not a therapeutic effect on renal damage induced by K2Cr2O7.

摘要

我们已经表明,在注射重铬酸钾(K2Cr2O7)24小时后,氯化亚锡(SnCl2)预处理对K2Cr2O7诱导的肾损伤的改善作用与血红素加氧酶-1(HO-1)的诱导有关。在这项工作中,我们评估了:(a)SnCl2(在K2Cr2O7之前12小时给予)的保护作用是否与K2Cr2O7注射后24小时和48小时肾组织中HO-1、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GPx)、谷胱甘肽还原酶(GR)和过氧化氢酶(CAT)活性的变化有关,以及(b)在K2Cr2O7注射前诱导HO-1是否必不可少。结果发现,SnCl2对肾功能的保护作用在24小时和48小时均可见,在24小时时达到最大,此时HO-1表达较高。在K2Cr2O7处理的大鼠中,Cu,Zn-SOD、Mn-SOD和GR活性保持不变,而在48小时时GPx和CAT活性降低。在SnCl2处理的大鼠中,Cu,Zn-SOD、Mn-SOD、GPx、CAT和GR的活性未发生变化。为了实现目标(b),在K2Cr2O7注射后24小时研究了用K2Cr2O7和SnCl2处理的大鼠组(同时给予或在K2Cr2O7后12小时给予)。同时注射SnCl2和K2Cr2O7没有保护作用,而在K2Cr2O7后12小时注射SnCl2会加重肾损伤。总之,SnCl2对K2Cr2O7诱导的肾毒性的保护作用与HO-1的诱导有关,而与其他抗氧化酶(Cu,Zn-SOD、Mn-SOD、GPx、GR和CAT)无关,并且SnCl2对K2Cr2O7诱导的肾损伤具有预防作用而非治疗作用。

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