Resveratrol attenuates acute kidney injury by inhibiting death receptor‑mediated apoptotic pathways in a cisplatin‑induced rat model.
Acute kidney injury is a clinical syndrome characterized by a loss of renal function and acute tubular necrosis. Resveratrol exerts a wide range of pharmacological effects based on its anti‑inflammatory, antioxidant and cytoprotective properties. The present study aimed to evaluate whether resveratrol attenuates acute kidney injury in a cisplatin‑induced rat model and to investigate the potential mechanisms involved. Rats were randomly divided into four treatment groups: control, cisplatin, resveratrol, and cisplatin plus resveratrol. Rats exposed to cisplatin displayed acute kidney injury, identified by analysis of renal function and histopathological observation. Resveratrol significantly ameliorated the increased serum creatinine, blood urea nitrogen, renal index and histopathological damage induced by cisplatin. Furthermore, compared with untreated control animals, cisplatin lead to significantly increased expression of Fas ligand, tumor necrosis factor‑α (TNF‑α), caspase‑8 and Bcl‑2 associated protein X apoptosis regulator (Bax), and decreased expression of anti‑apoptosis regulators, BH3 interacting domain death agonist (BID) and B cell lymphoma 2 apoptosis regulator (Bcl‑2). Administration of resveratrol significantly reversed the cisplatin‑induced alteration in these apoptosis‑associated proteins. In conclusion, these findings suggest that resveratrol attenuates cisplatin‑induced acute kidney injury through inactivation of the death receptor‑mediated apoptotic pathway, and may provide a new therapeutic strategy to ameliorate the process of acute kidney injury.
Department of Nephrology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
Qiufa
Q
Hao
Department of Nephrology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
Xiaoyan
X
Xiao
Department of Pathology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
Junhui
J
Zhen
Institute of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
Jinbo
J
Feng
Department of Pharmacy, Shandong University School of Pharmacy, Jinan, Shandong 250012, P.R. China.
Chun
C
Song
Department of Nephrology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
Bei
B
Jiang
Department of Nephrology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
Zhao
Z
Hu
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D002945:Cisplatin / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020011:Protective Agents / Q000627:therapeutic use*; D017208:Rats, Wistar; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D020011:Protective Agents; D013267:Stilbenes; D002945:Cisplatin; D000077185:Resveratrol