Ponalrestat, an aldose reductase inhibitor, inhibits cachexia syndrome induced by colon26 adenocarcinoma in mice

Our recent study has demonstrated that ponalrestat, an aldose reductase inh ibitor, activates lipoprotein lipase activity and alleviates B16 melanoma-i nduced cachexia in mice In this study, the effect of ponalrestat on murine adenocarcinoma colon26-induced cachexia was investigated in mice. Mice bear ing colon26 subcutaneously lost weight and became cachectic, associated wit h the tumor growth. Although tumor growth was slightly stimulated when tumo r bearing mice were treated with ponalrestat; nevertheless, the drug attenu ated the reduction in the weight of body mass, epididymal fat, gastrocnemiu s muscle and carcass induced by colon26, as well as significantly prolonged the survival of the colon26 bearing mice. Ponalrestat inhibited the produc tion of interleukin-1 (IL-1) from human monocytes stimulated by Lipopolysac charide (LPS) in vitro, and also suppressed LPS-induced increase of IL-1 in the blood in mice. Overall, this study showed that ponalrestat suppresses IL-1 production both in vitro and in vivo, and inhibits the cachectic sympt oms induced by colon26 adenocarcinoma in mice, suggesting that ponalrestat has a therapeutic potential for the treatment of cancer cachexia.