Ponalrestat, an aldose reductase inhibitor, inhibits cachexia syndrome in nude mice bearing human melanomas G361 and SEKI

Our recent study has demonstrated that ponalrestat, an aldose reductase inh ibitor; activates lipoprotein lipase (LPL) activity in the adipose tissue a nd alleviates the cachectic symptoms induced by B16 melanoma in mice. In th is study, the effect of ponalrestat on cachexia symptoms in nude mice beari ng human melanomas G361 and SEKI was investigated because it has been sugge sted that the suppression of LPL has an important role in cachexia inductio n by these two melanomas in nude mice. Mice bearing G361 subcutaneously did not gain weight and became cachectic, associated with the tumor growth. Tu mor growth was not affected by ponalrestat, nevertheless treatment with pon alrestat resulted in an amelioration of the reduction in the weight of body , mass, epididymal fat, gastrocnemius muscle, carcass and whole body lipid induced by the presence of G361. A severe weight loss observed in nude mice bearing SEKI was also partially attenuated by ponalrestat treatment. Overa ll, this study, showed that ponalrestat is effective in the attenuation of the cachectic symptoms induced by human melanomas G361 and SEKI in nude mic e, suggesting that ponalrestat has a potential usefulness for the treatment of cancel cachexia.