Action of celecoxib on hepatic metabolic changes induced by the Walker-256 tumour in rats.
The purpose of the present work was to investigate the influence of celecoxib on some hepatic metabolic parameters affected by the Walker-256 tumour in rats. Celecoxib was administered daily (5-50 mg/kg body weight) beginning at the day in which the tumour cells were inocculated. At day 14, the liver was isolated and perfused in order to measure alanine transformation, glycolysis and arginine transformation. Maximal reduction of tumour growth (75%), accompanied by an almost normal weight gain, was attained with a celecoxib dose of 12.5 mg/kg. Diminution of glucose utilization (glycolysis) and inhibition of gluconeogenesis and ureogenesis from alanine caused by the tumor were totally reversed by celecoxib. Oxygen uptake by the liver was also normalized by the drug. Hepatic arginine transformation, which is normally enhanced in rats bearing the Walker-256 tumour, remained elevated in celecoxib-treated animals. It was concluded that preservation of gluconeogenesis and normalization of hepatic glucose utilization can explain, partly at least, the clinical improvement of cancer patients treated with the drug. The lack of action of celecoxib on arginine hydrolysis might indicate that reduction in polyamine synthesis is not a factor contributing to the diminished tumour growth.
Acco
Alexandra
A
Department of Pharmacology, Federal University of Paraná, Curitiba, Brazil.
Alves da Silva
Mário Henrique da Rocha
MH
Batista
Márcia Regina
MR
Yamamoto
Nair Seiko
NS
Bracht
Adelar
A
D000409:Alanine / Q000378:metabolism; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000378:metabolism; D002279:Carcinoma 256, Walker / Q000378:metabolism* / Q000473:pathology; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D005943:Gluconeogenesis / Q000187:drug effects; D006019:Glycolysis / Q000187:drug effects; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009368:Neoplasm Transplantation; D010477:Perfusion; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D013449:Sulfonamides / Q000494:pharmacology*; D014508:Urea / Q000378:metabolism
D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000641:Ammonia; D014508:Urea; D001120:Arginine; D000068579:Celecoxib; D000409:Alanine