Involvement of lipoxygenase and cyclo-oxygenase pathways in hypoxia and metabolic alkalosis produced by canatoxin in rats.

This paper reports on the metabolic alkalosis produced in rats by canatoxin, a neurotoxic principle extracted from Canavalia ensiformis seeds. Rats receiving canatoxin showed increased blood bicarbonate concentration with alkaline pH and no change in pCO2. A fall in pO2 was also seen. A dose-dependent relationship between pO2 decrease and bicarbonate increase was also observed with the toxin, suggesting that hypoxia may result from respiratory compensation. Canatoxin-induced hypoxia was both lipoxygenase and cyclo-oxygenase dependent but metabolic alkalosis was only blocked with cyclo-oxygenase inhibitors. Canatoxin activates the lipoxygenase pathway and probably increases leukotriene (LT) production. Since LT may release cyclo-oxygenase products, this may explain the metabolic alkalosis observed with canatoxin.