Evaluation of Effectiveness of Oral D-methionine on Nephrotoxicity and Anorexia/Cachexia Induced by Chronic Cisplatin Administration Toxicity Model

• Main Authors: Hui-Yi Chang, 張惠怡
• Other Authors: 歐珠琴
• Format: Others
• Language: zh-TW
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/mpvq76

碩士 === 中山醫學大學 === 營養學研究所 === 104 === Cisplatin is a widely used chemotherapeutic agent for the treatment of solid tumors. Its clinical use is limited due to severe side effects such as nephrotoxicity and anorexia/cachexia. Many sulfur containing compounds have been reported to protect against cisplatin-induced cytotoxicity. D-methionine, dextro-isomer of L-methionine, is a sulfur containing amino acid and can act as potent antioxidants. In this study, we investigate the effects of oral D-methionine on cisplatin-induced nephrotoxicity and anorexia/cachexia. Male Wistar rats were divided into three treatment groups of eight rats each. The study schedule was designed in a chronic experiment model, which rats received cisplatin (5 mg/kg body wt) intraperitoneal injection once a week for 3 weeks (cisplatin group). The animals were pre-treated with D-methionine (300 mg/kg body wt) daily by gavage for 3 days before cisplatin administration (cisplatin combined D-methionine group). The control group remains untreated. The results suggested that D-methionine significantly reverse the reduction of body weight, increase daily food intake, and enhance gastric emptying after cisplatin treatment. We also observed that cisplatin suppresses lipogensis in liver tissues and up-regulates the muscle atrophy markers gene expression (such as FOXO1, MAFbx). The loss of skeletal muscles mass and adipose tissue are regained by D-methionine administration, which might be partly through retard liver lipogensis and modulated muscle atrophy-related mRNA expression. On the other hand, we found the treatment with D-methionine mitigates the cisplatin nephrotoxicity which caused the increasing level of blood urea nitrogen (BUN) and the renal inflammation. Histopathological examination revealed that D-methionine improved severe renal damage induced by cisplatin. Moreover, the renal malondialdehyde (MDA) production in cisplatin-administrated rats was markedly increased and the activity of glutathione peroxidase (GPx) and glutathione (GSH) content were also declined. D-methionine significantly attenuated the above oxidative stress markers caused by cisplatin. Our result indicated that oral D-methionine could protect against cisplatin-induced nephrotoxicity and anorexia/cachexia. Therefore, D-methionine has the potential to alleviate the side effects of cisplatin and serve as novel nutritional supplements when patients are undergoing their chemotherapy.