Kim Eun-Sun, Lee Jong Soo, Akram Muhammad, Kim Kyeong-A, Shin Young-Jun, Yu Jong-Hyun, Bae Ok-Nam
College of Pharmacy Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Republic of Korea.
Kidney Blood Press Res. 2015;40(1):1-12. doi: 10.1159/000368466. Epub 2015 Jan 25.
BACKGROUND/AIMS: Drug-induced acute kidney injury (AKI) has been a severe threat to hospitalized patients, raising the urgent needs to develop strategies to reduce AKI. We investigated the protective activity of Dendropanax morbifera (DP), a medicinal plant which has been widely used to treat infectious and pain diseases, on acute kidney injury (AKI) using cisplatin-induced nephropathic models.
Both in vitro renal tubular cells (NRK-52E) and in vivo rat models were used to demonstrate the nephroprotective effect of DP.
Methanolic extract from DP significantly reduced cisplatin-induced toxicity in renal tubular cells. Through successive liquid extraction, the extract of DP was separated into n-hexane, CHCl3, EtOAc, n-BuOH, and H2O fractions. Among these, the CHCl3 fraction (DPCF) was found to be most potent. The protective activity of DPCF was found to be mediated through anti-oxidant, mitochondrial protective, and anti-apoptotic activities. In in vivo rat models of AKI, treatment with DPCF significantly reversed the cisplatin-induced increase in blood urea nitrogen and serum creatinine and histopathologic damage, recovered the level of anti-oxidant enzymes, and inhibited renal apoptosis.
We demonstrated that DP extracts decreased cisplatin-induced renal toxicity, indicating its potential to ameliorate drug-associated acute kidney damage.
背景/目的:药物性急性肾损伤(AKI)一直是住院患者面临的严重威胁,因此迫切需要制定降低AKI的策略。我们使用顺铂诱导的肾病模型,研究了广泛用于治疗感染性疾病和疼痛性疾病的药用植物辽东楤木(DP)对急性肾损伤(AKI)的保护作用。
采用体外肾小管细胞(NRK-52E)和体内大鼠模型来证明DP的肾保护作用。
DP的甲醇提取物显著降低了顺铂对肾小管细胞的毒性。通过连续液液萃取,DP提取物被分离为正己烷、氯仿、乙酸乙酯、正丁醇和水相部分。其中,氯仿部分(DPCF)的活性最强。发现DPCF的保护作用是通过抗氧化、线粒体保护和抗凋亡活性介导的。在AKI的体内大鼠模型中,用DPCF治疗可显著逆转顺铂诱导的血尿素氮和血清肌酐升高以及组织病理学损伤,恢复抗氧化酶水平,并抑制肾细胞凋亡。
我们证明了DP提取物可降低顺铂诱导的肾毒性,表明其具有改善药物相关性急性肾损伤的潜力。