Qi Zhang1, Qiuhong Sun2, Yan Tong1, Xiao Bi1, Lin Chen1, Jianxin Lu3, Wei Ding4. 1. Division of Nephrology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, 639 Zhizaoju Road, Shanghai, 200011, China. 2. Zibo Center for Disease Control and Prevention, 44 Dongyi Road, Shandong, 255020, China. 3. Division of Nephrology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, 639 Zhizaoju Road, Shanghai, 200011, China. lujxswuu@126.com. 4. Division of Nephrology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, 639 Zhizaoju Road, Shanghai, 200011, China. gump1015@163.com.
Abstract
PURPOSE: Cisplatin has been widely accepted as an effective chemotherapy drug with various side effects, including nephrotoxicity. The mechanisms of cisplatin-induced acute kidney injury (AKI) are complex, and there are limited renoprotective approaches. Leonurine is the main active compound of a Chinese herb and has recently been reported to have a protective effect on the kidneys. This study aimed to verify the renoprotective effect of leonurine in attenuating cisplatin-induced AKI and explore the potential associated mechanisms. METHODS: C57BL/6 mice were divided into four groups (Sham, Cisplatin, Leonurine, and Cisplatin + Leonurine). Mice in the leonurine-treated groups were pretreated with a daily intraperitoneal injection of 25 mg/kg leonurine. AKI was induced by injecting cisplatin once intraperitoneally at 20 mg/kg body weight. Mice were killed on day 5. Kidney injury was assessed using a serum biochemical and histological assay. Apoptosis was evaluated using a terminal deoxyribonucleotide transferase-mediated dUTP nick-end labeling (TUNEL) staining assay and Western blot. Antioxidant enzymes were detected using commercial kits. The improvement in inflammasome activation, mitochondrial dysfunction, and endoplasmic reticulum stress (ERS) were assessed by polymerase chain reaction (PCR) and Western blot, respectively. RESULTS: Leonurine treatment improved kidney function by preventing renal tubular injury and apoptosis. Expression of nucleotide-binding leucine-rich repeat and pyrin domain containing protein 3 (NLRP3) inflammasome components and inflammatory cytokines, mitochondrial dysfunction, and ERS were all alleviated by leonurine. CONCLUSION: The results indicate that leonurine plays a protective role in cisplatin-induced AKI and may represent an effective multi-targeted intervention strategy.
PURPOSE: Cisplatin has been widely accepted as an effective chemotherapy drug with various side effects, including nephrotoxicity. The mechanisms of cisplatin-induced acute kidney injury (AKI) are complex, and there are limited renoprotective approaches. Leonurine is the main active compound of a Chinese herb and has recently been reported to have a protective effect on the kidneys. This study aimed to verify the renoprotective effect of leonurine in attenuating cisplatin-induced AKI and explore the potential associated mechanisms. METHODS: C57BL/6 mice were divided into four groups (Sham, Cisplatin, Leonurine, and Cisplatin + Leonurine). Mice in the leonurine-treated groups were pretreated with a daily intraperitoneal injection of 25 mg/kg leonurine. AKI was induced by injecting cisplatin once intraperitoneally at 20 mg/kg body weight. Mice were killed on day 5. Kidney injury was assessed using a serum biochemical and histological assay. Apoptosis was evaluated using a terminal deoxyribonucleotide transferase-mediated dUTP nick-end labeling (TUNEL) staining assay and Western blot. Antioxidant enzymes were detected using commercial kits. The improvement in inflammasome activation, mitochondrial dysfunction, and endoplasmic reticulum stress (ERS) were assessed by polymerase chain reaction (PCR) and Western blot, respectively. RESULTS: Leonurine treatment improved kidney function by preventing renal tubular injury and apoptosis. Expression of nucleotide-binding leucine-rich repeat and pyrin domain containing protein 3 (NLRP3) inflammasome components and inflammatory cytokines, mitochondrial dysfunction, and ERS were all alleviated by leonurine. CONCLUSION: The results indicate that leonurine plays a protective role in cisplatin-induced AKI and may represent an effective multi-targeted intervention strategy.
Authors: Amandeep Bajwa; Diane L Rosin; Piotr Chroscicki; Sangju Lee; Krishna Dondeti; Hong Ye; Gilbert R Kinsey; Brian K Stevens; Katarzyna Jobin; Brandon M Kenwood; Kyle L Hoehn; Kevin R Lynch; Mark D Okusa Journal: J Am Soc Nephrol Date: 2014-08-21 Impact factor: 10.121