Luan He1, Yong Zhang2, Naixin Kang1, Yaner Wang3, Ziyu Zhang1, Zhengxia Zha2, Shilin Yang1, Qiongming Xu4, Yanli Liu5. 1. Department of Pharmacognosy, College of Pharmaceutical Science, Soochow University, Suzhou, Jiangsu province 215123, China. 2. Department of Pharmacology, College of Pharmaceutical Science, Soochow University, Suzhou 215123, China. 3. Department of Pharmacognosy, College of Pharmaceutical Science, Soochow University, Suzhou, Jiangsu province 215123, China; Department of Pharmacology, College of Pharmaceutical Science, Soochow University, Suzhou 215123, China. 4. Department of Pharmacognosy, College of Pharmaceutical Science, Soochow University, Suzhou, Jiangsu province 215123, China; College of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530000, China. Electronic address: liuyanli@suda.edu.cn. 5. Department of Pharmacology, College of Pharmaceutical Science, Soochow University, Suzhou 215123, China. Electronic address: liuyanli@suda.edu.cn.
Abstract
BACKGROUND: Cisplatin is a highly effective chemotherapeutic agent commonly used in the treatment of a wide variety of malignancies. However, its clinical usage is severely limited by its serious side effects, especially nephrotoxicity. Anemoside B4, is a major saponins, rich in root of Pulsatilla chinensis (Bunge), has anti-inflammation in vitro. However, the antioxidant or anti-inflammatory effects of anemoside B4 in cisplatin-induced nephrotoxicity have not been clearly demonstrated. PURPOSE: In this study, we investigated whether anemoside B4 exhibits protective effects against cisplatin-induced nephrotoxicity involving antioxidant or anti-apoptosis effects. METHOD: To clarify it, the effects of anemoside B4 on HEK 293 cell viability was measured by CCK8 kits, intracellular antioxidant capacity including glutathione reduced (GSH), catalase (CAT) were estimated using chemical kits, apoptosis rate and intracellular reactive oxygen species (ROS) was analyzed by flow cytometry, apoptosis protein was measured by western blotting. In vivo model of cisplatin-induced mice acute renal failure was performed to evaluate the properties of anemoside B4. Besides, to evaluate the effect of anemoside B4 on the anti-tumor activity of cisplatin, S180 xenograft models were used. RESULTS: Anemoside B4 potently increased cisplatin-treated HEK 293T cells viability on the concentration and time manners and inhibited cells apoptosis, as demonstrated by the decreased cleaved PARP protein expressions. Anemoside B4 decreased reactive oxygen species (ROS) content and improved superoxide dismutase (SOD) activity. In vivo experiment showed that pretreatment with anemoside B4 effectively adjusted body weight and kidney index, and reduced cisplatin-elevated blood urea nitrogen (BUN) and creatinine (CREA) levels, as well as ameliorated the histopathological damage. Further studies showed that anemoside B4 did not reduce antitumor activity of cisplatin in murine S180 cancer xenograft tumor models. In addition, anemoside B4 per set showed low toxicity in mice. CONCLUSION: The strong antioxidant and anti-apoptosis effects of anemoside B4 may provide therapeutic potential for cisplatin-induced nephrotoxicity without compromising its therapeutic efficiency.
BACKGROUND:Cisplatin is a highly effective chemotherapeutic agent commonly used in the treatment of a wide variety of malignancies. However, its clinical usage is severely limited by its serious side effects, especially nephrotoxicity. Anemoside B4, is a major saponins, rich in root of Pulsatilla chinensis (Bunge), has anti-inflammation in vitro. However, the antioxidant or anti-inflammatory effects of anemoside B4 in cisplatin-induced nephrotoxicity have not been clearly demonstrated. PURPOSE: In this study, we investigated whether anemoside B4 exhibits protective effects against cisplatin-induced nephrotoxicity involving antioxidant or anti-apoptosis effects. METHOD: To clarify it, the effects of anemoside B4 on HEK 293 cell viability was measured by CCK8 kits, intracellular antioxidant capacity including glutathione reduced (GSH), catalase (CAT) were estimated using chemical kits, apoptosis rate and intracellular reactive oxygen species (ROS) was analyzed by flow cytometry, apoptosis protein was measured by western blotting. In vivo model of cisplatin-induced miceacute renal failure was performed to evaluate the properties of anemoside B4. Besides, to evaluate the effect of anemoside B4 on the anti-tumor activity of cisplatin, S180 xenograft models were used. RESULTS:Anemoside B4 potently increased cisplatin-treated HEK 293T cells viability on the concentration and time manners and inhibited cells apoptosis, as demonstrated by the decreased cleaved PARP protein expressions. Anemoside B4 decreased reactive oxygen species (ROS) content and improved superoxide dismutase (SOD) activity. In vivo experiment showed that pretreatment with anemoside B4 effectively adjusted body weight and kidney index, and reduced cisplatin-elevated blood ureanitrogen (BUN) and creatinine (CREA) levels, as well as ameliorated the histopathological damage. Further studies showed that anemoside B4 did not reduce antitumor activity of cisplatin in murineS180 cancer xenograft tumor models. In addition, anemoside B4 per set showed low toxicity in mice. CONCLUSION: The strong antioxidant and anti-apoptosis effects of anemoside B4 may provide therapeutic potential for cisplatin-induced nephrotoxicity without compromising its therapeutic efficiency.