The protective effects of Ribes diacanthum Pall on cisplatin-induced nephrotoxicity in mice.
BACKGROUND
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.


CONCLUSIONS
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.
Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, Jiangsu 211198, China.
Akhtolkhyn
A
Tilyek
Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, Jiangsu 211198, China.
Chengzhi
C
Chai
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.
Xiaoli
X
Hou
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.
Baoping
B
Zhou
Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, Jiangsu 211198, China.
Chunlei
C
Zhang
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.
Zhengyu
Z
Cao
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.
Boyang
B
Yu
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001806:Blood Urea Nitrogen; D053148:Caspase 3 / Q000378:metabolism; D002945:Cisplatin / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry; D020011:Protective Agents / Q000737:chemistry / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D031965:Ribes / Q000737:chemistry*; D013482:Superoxide Dismutase / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D010936:Plant Extracts; D020011:Protective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D003404:Creatinine; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D053148:Caspase 3; D002945:Cisplatin
Apoptosis; Cisplatin; Nephrotoxicity/Nephropathology; Oxidative stress; Ribes diacanthum Pall