title: S-Allylmercaptocysteine Attenuates  Cisplatin-Induced Nephrotoxicity through  Suppression of Apoptosis, Oxidative Stress, and  Inflammation.
abstract: Cisplatin is a potent chemotherapeutic agent, but its clinical usage is limited by nephrotoxicity. S-allylmercaptocysteine (SAMC), one of the water-soluble organosulfur garlic derivatives, has antioxidant and anti-inflammatory properties and plays an important role in protecting cells from apoptosis. This study aims to examine the protective effects of SAMC on cisplatin nephrotoxicity and to explore the mechanism of its renoprotection. Rats were treated with cisplatin with or without pre-treatment with SAMC. Renal function, histological change, oxidative stress markers and antioxidant enzyme activities were investigated. Apoptotic marker, nuclearfactor (NF)-κB activity, expression of nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H:quinone oxidoreductase 1 (NQO1) and inflammatory cytokines were also examined. The effect of SAMC on cell viability and apoptosis was examined in cultured human kidney (HK-2) cells. SAMC was confirmed to significantly attenuate cisplatin-induced renal damage by using histological pathology and molecular biological method. Pre-treatment with SAMC reduced NF-κB activity, up-regulated Nrf2 and NQO1 expression and down-regulated inflammatory cytokine levels after cisplatin administration. Cisplatin-induced apoptosis in HK-2 cells was significantly attenuated by SAMC. Thus our results suggest that SAMC could be a potential therapeutic agent in the treatment of the cisplatin-induced nephrotoxicity through its anti-apoptotic, anti-oxidant and anti-inflammatory effects.
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan 250012, China. zxs_sdu@163.com.
authors.forename: Xiaosong
authors.initials: X
authors.lastname: Zhu
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan 250012, China. jiangxiaoyan1121@163.com.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Jiang
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan 250012, China. liangliang0725@aliyun.com.
authors.forename: Ang
authors.initials: A
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan 250012, China. uszxzhao@gmail.com.|Shandong Provincial Key Laboratory of Mucosal and Transdermal Drug Delivery Technologies, Shandong Academy of Pharmaceutical Sciences, 989 Xinluo Street, Jinan 250101, China. uszxzhao@gmail.com.
authors.forename: Zhongxi
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan 250012, China. siying@hotmail.com.
authors.forename: Siying
authors.initials: S
authors.lastname: Li
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000097:blood; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015536:Down-Regulation; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000187:drug effects; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015415:Biomarkers; D053583:Interleukin-1beta; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495635:NFE2L2 protein, human; C495637:Nfe2l2 protein, rat; C086300:S-allylmercaptocysteine; D014409:Tumor Necrosis Factor-alpha; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; C507703:NQO1 protein, rat; D003545:Cysteine; D002945:Cisplatin
keywords: cisplatin;  SAMC;  apoptosis;  inflammation;  oxidative stress