A Pre-Clinical Study of Sub-Anesthetic Ketamine as Remedy in 5-Fluorouracil-Induced Cachexia Model

Abstract

Around 0.5–1% of the world population is suffering from cachexia. In particular, cancer patients under cancer radio-chemotherapy have a high prevalence of cachexia, especially during the end stages of therapeutic treatment. Clinically, chemotherapeutic 5-fluorouracil (5-Fu) treatment often leads to the development of adverse effects, such as leukopenia, immune dysfunction, anorexia, muscle wasting, etc., and 5-Fu also tends to exacerbate the occurrence of cancer cachexia. Currently, there are very limited drug choices when seeking to revive cachexia patient’s health quality while enduring a full therapeutic regimen as part of advanced cancer therapy. The present study employed chemotherapeutic drug 5-Fu-induced cachexia-like conditions in Balb/c mice. After 8 days of 5-Fu treatment, mice had begun to show cachexia-like symptoms such as weight loss and reduced food intake. After one day of washing out, the cachexia animals received a single dose of either saline solution as a mock dose or a low dose (15 mg/kg BW) or high dose (30 mg/kg BW) of ketamine at day 10. For the following 7 days, food intake, body weight, and mortality were monitored. Data were analyzed with the LOCF (last observation carried forward) method. Improved survival rates were obtained in ketamine groups. Ketamine administration at the high dose of 30 mg/kg BW demonstrated effectively diminished weight loss due to cachexia, and also successfully improved overall survival. The current study demonstrates that a sub-anesthetic level of ketamine administration supports overall beneficial outcomes in 5-Fu-induced cachexia and outlook as a potential clinical remedy.