Effect of Magnesium Valproate in Cancer Cachexia and Association Cardiovascular Complications

Abstract

BACKGROUND AND OBJECTIVE: Cancer cachexia is complex, insidious syndrome characterized by loss or wasting of skeletal muscle mass with or without loss of fat mass that can be partially but not completely reversed by the nutritional support and also associated with poor response to chemotherapy and reduced quality of life. Cachexia is an energy wasting syndrome that causes skeletal muscle wasting and skeletal muscle atrophy. Emphasis is given to the inflammatory cascade activation and their responses to the tumor growth, which seems to trigger many of the metabolic changes which are associated with muscle wasting syndrome. Current anti-cancer agents are only beneficial in cancer treatment, and they are not able to treat cachexia. Moreover, they are associated with several toxicities including cardiotoxicity. Hence, agents which are beneficial in cancer cachexia and also exhibit cardioprotection are needed to be investigated. Magnesium valproate is an HDAC inhibitor, which is reported to exhibit anti-cancer properties, have benefit in skeletal muscle wasting and is cardioprotective in nature. Hence, the objective of the present study is to evaluate the effect of magnesium valproate in combination with cisplatin in cancer cachexia and associated cardiovascular complications.MATERIALS AND METHOD: The study was carried out using B16F1 induced metastatic cancer. BALB/c mice of either sex, at 10-12 weeks of age, weighing 25-35 g were taken for the study. A rapid injection of large volume B16F1 cell suspension (1×106) into the Balb/c mice tail vein was performed and allow to grow tumour for 21 days. On 21st day the treatment was started with magnesium valproate (200mg/kg) for 4 weeks and cisplatin (5mg/kg) is given on 1st and 21st day of treatment period. Parameters evaluated were body mass markers, inflammatory markers, markers of carbohydrate metabolism, marker of lipid metabolism, skeletal muscle wasting marker and cardiac complication markers. RESULT: Body mass marker: After the injection of B16F1 melanoma cell lines, a significant decrease in the body weight, food intake, water intake, carcass weight as compared to normal control animals. Treatment with magnesium valproate in combination with cisplatin produced a significant increase in the body weights, food intake, water intake, carcass weight when compared with disease control and disease treated with cisplatin. However, treatment with cisplatin alone did not produced any significant in the body weights, water intake, food intake and carcass weight were observed.