Antioxidants & redox signaling · 2018
Renal Protective Effect of Hydrogen Sulfide in Cisplatin-Induced Nephrotoxicity.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Cao Xu, Xiong Siping, Zhou Yebo, Wu Zhiyuan, Ding Lei, Zhu Yike, Wood Mark E, Whiteman Matthew, Moore Philip K, Bian Jin-Song
Аннотация
AIMS: Cisplatin is a major therapeutic drug for solid tumors, but can cause severe nephrotoxicity. However, the role and therapeutic potential of hydrogen sulfide (H2S), an endogenous gasotransmitter, in cisplatin-induced nephrotoxicity remain to be defined.
RESULTS: Cisplatin led to the impairment of H2S production in vitro and in vivo by downregulating the expression level of cystathionine γ-lyase (CSE), which may contribute to the subsequent renal proximal tubule (RPT) cell death and thereby renal toxicity. H2S donors NaHS and GYY4137, but not AP39, mitigated cisplatin-induced RPT cell death and nephrotoxicity. The mechanisms underlying the protective effect of H2S donors included the suppression of intracellular reactive oxygen species generation and downstream mitogen-activated protein kinases by inhibiting NADPH oxidase activity, which may be possibly through persulfidating the subunit p47phox. Importantly, GYY4137 not only ameliorated cisplatin-caused renal injury but also added on more anticancer effect to cisplatin in cancer cell lines. Innovation and Conclusion: Our study provides a comprehensive understanding of the role and therapeutic potential of H2S in cisplatin-induced nephrotoxicity. Our results indicate that H2S may be a novel and promising therapeutic target to prevent cisplatin-induced nephrotoxicity. Antioxid. Redox Signal. 29, 455-470.
RESULTS: Cisplatin led to the impairment of H2S production in vitro and in vivo by downregulating the expression level of cystathionine γ-lyase (CSE), which may contribute to the subsequent renal proximal tubule (RPT) cell death and thereby renal toxicity. H2S donors NaHS and GYY4137, but not AP39, mitigated cisplatin-induced RPT cell death and nephrotoxicity. The mechanisms underlying the protective effect of H2S donors included the suppression of intracellular reactive oxygen species generation and downstream mitogen-activated protein kinases by inhibiting NADPH oxidase activity, which may be possibly through persulfidating the subunit p47phox. Importantly, GYY4137 not only ameliorated cisplatin-caused renal injury but also added on more anticancer effect to cisplatin in cancer cell lines. Innovation and Conclusion: Our study provides a comprehensive understanding of the role and therapeutic potential of H2S in cisplatin-induced nephrotoxicity. Our results indicate that H2S may be a novel and promising therapeutic target to prevent cisplatin-induced nephrotoxicity. Antioxid. Redox Signal. 29, 455-470.