Soetikno Vivian, Sari Shinta Dewi Permata, Ul Maknun Lulu, Sumbung Nielda Kezia, Rahmi Deliana Nur Ihsani, Pandhita Bashar Adi Wahyu, Louisa Melva, Estuningtyas Ari
Department of Pharmacology and Therapeutic, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia.
Drug Res (Stuttg). 2019 Feb;69(2):75-82. doi: 10.1055/a-0641-5148. Epub 2018 Jun 26.
In addition to oxidative stress, inflammation and apoptosis have an important role in the pathogenesis of cisplatin-induced kidney damage. This study aimed to investigate the molecular mechanisms of protective effects of curcumin against cisplatin-induced kidney inflammation and apoptosis in rats.
Eighteen rats were equally divided into three groups; normal (0.5% CMC-Na), cisplatin (CDPP) (7 mg/kg i.p.), and cisplatin+curcumin (CMN100) groups. Curcumin was given at a dose of 100 mg/kg orally for nine days, starts one week before giving a single dose of cisplatin. Kidney and plasma were taken for analysis.
Cisplatin challenged rats demonstrated kidney injury as shown by reduced creatinine clearance, increased of plasma BUN, plasma creatinine, and kidney MDA, decreased of kidney GSH levels, and kidney histopathology alterations. Also, cisplatin increased ERK1/2 phosphorylation and NF-κB expression, which subsequently increased mRNA expression of TNF-α, IL-6, KIM-1, NGAL, and Bax/Bcl-2 ratio as well as decreased mRNA expression of IL-10 in kidney tissues. Pre-treatment with curcumin significantly ameliorated inflammation and apoptosis induced by cisplatin. In addition, curcumin downregulated Ctr1 and OCT2 drug transporters as compared to cisplatin group. Histopathological examination furthers confirmed the kidney damage protection effect of curcumin.
These data indicate that curcumin has nephroprotective properties against cisplatin-induced kidney damage in rats and this effect is associated with its anti-inflammatory and anti-apoptosis profiles, in addition to its antioxidant. Hence, curcumin may be useful for preventing kidney damage against cisplatin administration.
除氧化应激外，炎症和细胞凋亡在顺铂诱导的肾损伤发病机制中起重要作用。本研究旨在探讨姜黄素对顺铂诱导的大鼠肾脏炎症和细胞凋亡的保护作用的分子机制。
18只大鼠平均分为三组；正常组（0.5%羧甲基纤维素钠）、顺铂组（CDPP）（腹腔注射7mg/kg）和顺铂+姜黄素组（CMN100）。在给予单剂量顺铂前一周开始，姜黄素以100mg/kg的剂量口服给药九天。采集肾脏和血浆进行分析。
顺铂攻击的大鼠表现出肾损伤，表现为肌酐清除率降低、血浆尿素氮、血浆肌酐和肾脏丙二醛升高、肾脏谷胱甘肽水平降低以及肾脏组织病理学改变。此外，顺铂增加了ERK1/2磷酸化和NF-κB表达，随后增加了肾脏组织中TNF-α、IL-6、KIM-1、NGAL的mRNA表达以及Bax/Bcl-2比值，并降低了IL-10的mRNA表达。姜黄素预处理显著改善了顺铂诱导的炎症和细胞凋亡。此外，与顺铂组相比，姜黄素下调了Ctr1和OCT2药物转运体。组织病理学检查进一步证实了姜黄素对肾脏损伤的保护作用。
这些数据表明，姜黄素对顺铂诱导的大鼠肾损伤具有肾保护作用，除了其抗氧化作用外，这种作用还与其抗炎和抗凋亡特性有关。因此，姜黄素可能有助于预防顺铂给药引起的肾损伤。
