Cisplatin is a widely used anti-cancer drug. However, cisplatin is limited in clinical treatment because of its severe nephrotoxicity. This study reported whether O-GSP can antagonize the cisplatin-induced cytotoxicity in HEK293 cells through inducing HO-1 protein expression. We previously demonstrated O-GSP can increase the survival rate of HEK293 and have protective effect on HEK293 cells. Herein, We found that O-GSP can antagonize cisplatin nephrotoxicity through regulating the expression of HO-1. O-GSP promotes the translocation of Nrf2 in the nucleus, and activates the ERKN JNK pathway and p38 MAPK pathway. Interestingly, p38 MAPK plays a major role in HO-1 expression induced by O-GSP. And O-GSP can modulate the decrease of Nrf2 and HO-1 expression induced by cisplatin, and improve the cisplatin-induced activity and apoptosis rate of cells by stimulating the expression of HO-1. However, the protective effects of O-GSP are inhibited by ZnPP IX. Collectively, the results indicated that O-GSP induced the expression of HO-1 through p38MAPK and Nrf2 pathway in HEK293 cells.

中文翻译：

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葡萄籽原花青素可通过体外调节血红素加氧酶-1减轻顺铂诱导的人胚肾细胞的细胞毒性。

顺铂是一种广泛使用的抗癌药。但是，顺铂由于严重的肾毒性而在临床治疗中受到限制。这项研究报道了O-GSP是否可以通过诱导HO-1蛋白表达来拮抗顺铂诱导的HEK293细胞的细胞毒性。先前我们证明了O-GSP可以提高HEK293的存活率，并对HEK293细胞具有保护作用。在本文中，我们发现O-GSP可以通过调节HO-1的表达来拮抗顺铂的肾毒性。O-GSP促进Nrf2在细胞核中的移位，并激活ERKN JNK途径和p38 MAPK途径。有趣的是，p38 MAPK在O-GSP诱导的HO-1表达中起主要作用。O-GSP可调节顺铂诱导的Nrf2和HO-1表达的降低，通过刺激HO-1的表达提高顺铂诱导的细胞活性和凋亡率。但是，ZnPP IX抑制了O-GSP的保护作用。总体而言，结果表明O-GSP通过p38MAPK和Nrf2途径诱导HEK293细胞中HO-1的表达。