Akhtolkhyn Tilyek1, Chengzhi Chai1, Xiaoli Hou2, Baoping Zhou2, Chunlei Zhang1, Zhengyu Cao3, Boyang Yu4. 1. Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, Jiangsu 211198, China. 2. Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, Jiangsu 211198, China; Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational Research, China Pharmaceutical University, Nanjing, Jiangsu 211198, China. 3. Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, Jiangsu 211198, China; Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational Research, China Pharmaceutical University, Nanjing, Jiangsu 211198, China. Electronic address: zycao1999@hotmail.com. 4. Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, Jiangsu 211198, China; Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational Research, China Pharmaceutical University, Nanjing, Jiangsu 211198, China. Electronic address: boyangyu59@163.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Ribes diacanthum Pall. (Saxifragaceae), a Mongolian folk medicinal plant, was used to treat urinary system diseases. The present work aims to investigate the protective effects of Ribes diacanthum Pall (RDP) against cisplatin-induced nephrotoxicity. METHODS: The renal injury was modeled by intraperitoneal injection of cisplatin for 5 consecutive days (5 mg/kg). Nephroprotection of RDP was investigated by oral administration of RDP aqueous extract at a daily dose of 40 mg/kg for 14 consecutive days, starting 7 days prior to cisplatin administration. RESULTS: We demonstrated that pretreatment with RDP aqueous extract protected the mice from death induced by cisplatin administration. RDP treatment also significantly reduced blood urea nitrogen (BUN) and serum creatinine (Cr) levels observed in cisplatin-administrated mice. Histopathological analysis demonstrated that RDP administration protected cisplatin-induced renal tubular cell apoptosis. Further western blotting analysis revealed that RDP significantly reversed cisplatin-increased expression levels of cleaved-Caspase-3, Bax and cisplatin-decreased expression level of Bcl-2 in renal tissue. Finally, RDP markedly enhanced enzyme activities of reduced superoxide dismutase (SOD), Heme oxygenase 1 (HO-1) and catalase (CAT), suppressed lipid peroxidation as well as reactive oxygen species (ROS) production. CONCLUSION: We concluded that RDP displayed nephroprotective effects against cisplatin-induced renal tubular cell apoptosis, possibly associated with both enhanced antioxidase activity and suppressed ROS generation. Given the major nephrotoxicity of cisplatin cancer chemotherapy, RDP might be a potential candidate for neoadjuvant chemotherapy.
ETHNOPHARMACOLOGICAL RELEVANCE: Ribes diacanthum Pall. (Saxifragaceae), a Mongolian folk medicinal plant, was used to treat urinary system diseases. The present work aims to investigate the protective effects of Ribes diacanthum Pall (RDP) against cisplatin-induced nephrotoxicity. METHODS: The renal injury was modeled by intraperitoneal injection of cisplatin for 5 consecutive days (5 mg/kg). Nephroprotection of RDP was investigated by oral administration of RDP aqueous extract at a daily dose of 40 mg/kg for 14 consecutive days, starting 7 days prior to cisplatin administration. RESULTS: We demonstrated that pretreatment with RDP aqueous extract protected the mice from death induced by cisplatin administration. RDP treatment also significantly reduced blood ureanitrogen (BUN) and serum creatinine (Cr) levels observed in cisplatin-administrated mice. Histopathological analysis demonstrated that RDP administration protected cisplatin-induced renal tubular cell apoptosis. Further western blotting analysis revealed that RDP significantly reversed cisplatin-increased expression levels of cleaved-Caspase-3, Bax and cisplatin-decreased expression level of Bcl-2 in renal tissue. Finally, RDP markedly enhanced enzyme activities of reduced superoxide dismutase (SOD), Heme oxygenase 1 (HO-1) and catalase (CAT), suppressed lipid peroxidation as well as reactive oxygen species (ROS) production. CONCLUSION: We concluded that RDP displayed nephroprotective effects against cisplatin-induced renal tubular cell apoptosis, possibly associated with both enhanced antioxidase activity and suppressed ROS generation. Given the major nephrotoxicity of cisplatincancer chemotherapy, RDP might be a potential candidate for neoadjuvant chemotherapy.
Authors: Sara J Holditch; Carolyn N Brown; Andrew M Lombardi; Khoa N Nguyen; Charles L Edelstein Journal: Int J Mol Sci Date: 2019-06-20 Impact factor: 5.923