College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China.
College of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530001, China.
Int J Mol Sci. 2017 Jul 13;18(7):1407. doi: 10.3390/ijms18071407.
Although cisplatin is an anticancer drug that has activity against malignant tumor, it often causes nephrotoxicity. Previous reports have confirmed that the saponins from the leaves of (PQS) exerted many pharmacological activities. However, the renoprotective effects of PQS were still unknown. The purpose of the present research was to discuss renoprotective effect of PQS in a mouse model of cisplatin-induced acute kidney injury (AKI). The levels of blood urea nitrogen (BUN) and serum creatinine (CRE) were evidently increased in cisplatin-intoxicated mice, which were reversed by PQS. Renal oxidative stress, evidenced by increased malondialdehyde (MDA) level and decline of glutathione (GSH) and superoxide dismutase (SOD) activities, was significantly alleviated by PQS pretreatment. The suppression of inflammatory response by PQS was realized through the decrease the mRNA expression levels of tumor necrosis factor-α () and interleukin-1β () in kidney tissues, which were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Simultaneously, the overexpression of cytochrome P450 E1 (CYP2E1) and heme oxygenase-1 (HO-1) were attenuated by PQS. Furthermore, the effects of Western blotting demonstrated that PQS administration significantly suppressed the protein expression levels of nicotinamide adenine dinucleotide phosphate oxidase type 4 (Nox4), cleaved Caspase-3, cleaved Caspase-9, Bax, nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS), suggesting the inhibition of apoptosis and inflammation response. Overall, PQS may possess protective effects in cisplatin-induced AKI through suppression of oxidative stress, inflammation and apoptosis.
顺铂是一种具有抗肿瘤活性的抗癌药物,但常导致肾毒性。先前的报告已经证实, (PQS)叶中的皂苷具有多种药理活性。然而,PQS 的肾保护作用尚不清楚。本研究旨在探讨 PQS 在顺铂诱导的急性肾损伤(AKI)小鼠模型中的肾保护作用。顺铂中毒小鼠的血尿素氮(BUN)和血清肌酐(CRE)水平明显升高,PQS 可逆转这一现象。肾氧化应激,表现为丙二醛(MDA)水平升高,谷胱甘肽(GSH)和超氧化物歧化酶(SOD)活性下降,经 PQS 预处理后明显缓解。通过定量实时聚合酶链反应(qRT-PCR)测量肾组织中肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)的 mRNA 表达水平,发现 PQS 抑制炎症反应。同时,PQS 减弱细胞色素 P450 E1(CYP2E1)和血红素加氧酶-1(HO-1)的过表达。此外,Western blot 结果表明,PQS 给药可显著抑制烟酰胺腺嘌呤二核苷酸磷酸氧化酶 4(Nox4)、裂解 Caspase-3、裂解 Caspase-9、Bax、核因子-κB(NF-κB)、环氧化酶-2(COX-2)和诱导型一氧化氮合酶(iNOS)的蛋白表达水平,提示抑制细胞凋亡和炎症反应。总之,PQS 可能通过抑制氧化应激、炎症和细胞凋亡对顺铂诱导的 AKI 具有保护作用。