Kim Ji Su, Kim Kyeong Seok, Son Ji Yeon, Kim Hae Ri, Park Jae Hyeon, Lee Su Hyun, Lee Da Eun, Kim In Su, Lee Kwang Youl, Lee Byung Mu, Kwak Jong Hwan, Kim Hyung Sik
Division of Toxicology, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.
Division of Molecular biology, College of Pharmacy & Research Institute of Drug Development, Chonnam National University, Gwangju 61186, Korea.
Antioxidants (Basel). 2019 Jul 30;8(8):256. doi: 10.3390/antiox8080256.
Use of the chemotherapeutic agent cisplatin (CDDP) in cancer patients is limited by the occurrence of acute kidney injury (AKI); however, no protective therapy is available. We aimed to investigate the renoprotective effects of water extract (DM) on CDDP-induced AKI. Male Sprague-Dawley rats (six animals/group) received: Vehicle (control); CDDP (6 mg/kg, intraperitoneally (i.p.); DM (25 mg/kg, oral); or DM + CDDP injection. CDDP treatment significantly increased blood urea nitrogen (BUN), serum creatinine (sCr), and pro-inflammatory cytokines (IL-6 and TNF-α), and severely damaged the kidney architecture. Urinary excretion of protein-based AKI biomarkers also increased in the CDDP-treated group. In contrast, DM ameliorated CDDP-induced AKI biomarkers. It markedly protected against CDDP-induced oxidative stress by increasing the activity of endogenous antioxidants and reducing the levels of pro-inflammatory cytokines (IL-6 and TNF-α). The protective effect of DM in the proximal tubules was evident upon histopathological examination. In a tumor xenograft model, administration of DM enhanced the chemotherapeutic activity of CDDP and exhibited renoprotective effects against CDDP-induced nephrotoxicity without altering chemotherapeutic efficacy. Our data demonstrate that DM may be an adjuvant therapy with CDDP in solid tumor patients to preserve renal function.
癌症患者使用化疗药物顺铂(CDDP)会受到急性肾损伤(AKI)的限制;然而,目前尚无保护性治疗方法。我们旨在研究水提取物(DM)对顺铂诱导的急性肾损伤的肾脏保护作用。雄性Sprague-Dawley大鼠(每组6只动物)接受以下处理:溶剂(对照);顺铂(6mg/kg,腹腔注射(i.p.));DM(25mg/kg,口服);或DM+顺铂注射。顺铂治疗显著增加了血尿素氮(BUN)、血清肌酐(sCr)和促炎细胞因子(IL-6和TNF-α),并严重破坏了肾脏结构。顺铂治疗组中基于蛋白质的急性肾损伤生物标志物的尿排泄也增加。相比之下,DM改善了顺铂诱导的急性肾损伤生物标志物。它通过增加内源性抗氧化剂的活性和降低促炎细胞因子(IL-6和TNF-α)的水平,显著保护免受顺铂诱导的氧化应激。组织病理学检查显示DM对近端小管有明显的保护作用。在肿瘤异种移植模型中,给予DM增强了顺铂的化疗活性,并对顺铂诱导的肾毒性表现出肾脏保护作用,而不改变化疗疗效。我们的数据表明,DM可能是实体瘤患者中与顺铂联合使用的辅助治疗方法,以保护肾功能。