Barrera Diana, Maldonado Perla D, Medina-Campos Omar N, Hernández-Pando Rogelio, Ibarra-Rubio María E, Pedraza-Chaverrí José
Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, Edificio B, Segundo Piso, Lab 209, Ciudad Universitaria, 04510 México, DF, México.
Life Sci. 2003 Oct 24;73(23):3027-41. doi: 10.1016/j.lfs.2003.06.002.
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.
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。
