Ponalrestat, an aldose reductase inhibitor, inhibits cachexia syndrome induced by colon26 adenocarcinoma in mice.
Our recent study has demonstrated that ponalrestat, an aldose reductase inhibitor, activates lipoprotein lipase activity and alleviates B16 melanoma-induced cachexia in mice. In this study, the effect of ponalrestat on murine adenocarcinoma colon26-induced cachexia was investigated in mice. Mice bearing colon26 subcutaneously lost weight and became cachectic, associated with the tumor growth. Although tumor growth was slightly stimulated when tumor bearing mice were treated with ponalrestat: nevertheless, the drug attenuated the reduction in the weight of body mass, epididymal fat, gastrocnemius muscle and carcass induced by colon26, as well as significantly prolonged the survival of the colon26 bearing mice. Ponalrestat inhibited the production of interleukin-1 (IL-1) from human monocytes stimulated by Lipopolysaccharide (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 symptoms induced by colon26 adenocarcinoma in mice, suggesting that ponalrestat has a therapeutic potential for the treatment of cancer cachexia.
Kawamura
I
I
Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan. ikuokawamura@po.fujisawa.co.jp
Lacey
E
E
Yamamoto
N
N
Sakai
F
F
Takeshita
S
S
Inami
M
M
Nishigaki
F
F
Naoe
Y
Y
Tsujimoto
S
S
Manda
T
T
Shimomura
K
K
Goto
T
T
D000230:Adenocarcinoma / Q000150:complications*; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002100:Cachexia / Q000188:drug therapy* / Q000209:etiology; D003110:Colonic Neoplasms / Q000150:complications*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004822:Epididymis / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000097:blood; D008070:Lipopolysaccharides / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects; D009368:Neoplasm Transplantation; D010793:Phthalazines / Q000494:pharmacology*; D013997:Time Factors
D004791:Enzyme Inhibitors; D007375:Interleukin-1; D008070:Lipopolysaccharides; D010793:Phthalazines; C042829:ponalrestat; D000449:Aldehyde Reductase