Baek Seung-Hoon, Shin Byong-Kyu, Kim Nam Jae, Chang Sun-Young, Park Jeong Hill
College of Pharmacy, Ajou University, Suwon, Republic of Korea.
Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon, Republic of Korea.
J Ginseng Res. 2017 Jul;41(3):233-239. doi: 10.1016/j.jgr.2016.03.008. Epub 2016 Apr 6.
Nephrotoxicity is the major side effect in cisplatin chemotherapy. Previously, we reported that the ginsenosides Rk3 and Rh4 reduced cisplatin toxicity on porcine renal proximal epithelial tubular cells (LLC-PK1). Here, we aimed to evaluate the protective effect of ginsenosides Rk3 and Rh4 on kidney function and elucidate their antioxidant effect using and models of cisplatin-induced acute renal failure.
An enriched mixture of ginsenosides Rk3 and Rh4 (KG-KH; 49.3% and 43.1%, respectively) was purified from sun ginseng (heat processed ). Cytotoxicity was induced by treatment of 20μM cisplatin to LLC-PK1 cells and rat model of acute renal failure was generated by single intraperitoneal injection of 5 mg/kg cisplatin. Protective effects were assessed by determining cell viability, reactive oxygen species generation, blood urea nitrogen, serum creatinine, antioxidant enzyme activity, and histopathological examination.
The assay demonstrated that KG-KH (50 μg/mL) significantly increased cell viability (4.6-fold), superoxide dismutase activity (2.8-fold), and glutathione reductase activity (1.5-fold), but reduced reactive oxygen species generation (56%) compared to cisplatin control cells. KG-KH (6 mg/kg, ) also significantly inhibited renal edema (87% kidney index) and dysfunction (71.4% blood urea nitrogen, 67.4% creatinine) compared to cisplatin control rats. Of note, KG-KH significantly recovered the kidney levels of catalase (1.2-fold) and superoxide dismutase (1.5-fold).
Considering the oxidative injury as an early trigger of cisplatin nephrotoxicity, our findings suggest that ginsenosides Rk3 and Rh4 protect the kidney from cisplatin-induced oxidative injury and help to recover renal function by restoring intrinsic antioxidant defenses.
肾毒性是顺铂化疗的主要副作用。此前，我们报道人参皂苷Rk3和Rh4可降低顺铂对猪肾近端上皮肾小管细胞（LLC-PK1）的毒性。在此，我们旨在评估人参皂苷Rk3和Rh4对肾功能的保护作用，并使用顺铂诱导的急性肾衰竭模型阐明其抗氧化作用。
从红参（热处理）中纯化出人参皂苷Rk3和Rh4的富集混合物（KG-KH；分别为49.3%和43.1%）。用20μM顺铂处理LLC-PK1细胞诱导细胞毒性，并通过单次腹腔注射5mg/kg顺铂建立大鼠急性肾衰竭模型。通过测定细胞活力、活性氧生成、血尿素氮、血清肌酐、抗氧化酶活性和组织病理学检查来评估保护作用。
MTT试验表明，与顺铂对照细胞相比，KG-KH（50μg/mL）显著提高细胞活力（4.6倍）、超氧化物歧化酶活性（2.8倍）和谷胱甘肽还原酶活性（1.5倍），但减少活性氧生成（56%）。与顺铂对照大鼠相比，KG-KH（6mg/kg，腹腔注射）也显著抑制肾水肿（肾指数降低87%）和功能障碍（血尿素氮降低71.4%，肌酐降低67.4%）。值得注意的是，KG-KH显著恢复了肾脏过氧化氢酶水平（1.2倍）和超氧化物歧化酶水平（1.5倍）。
考虑到氧化损伤是顺铂肾毒性的早期触发因素，我们的研究结果表明，人参皂苷Rk3和Rh4可保护肾脏免受顺铂诱导的氧化损伤，并通过恢复内在抗氧化防御来帮助恢复肾功能。
