Hyperglycemic effect of a neurotoxic fraction (F3) from Naja haje venom: role of hypothalamo-pituitary adrenal axis (HPA).

The effect of bolus intravenous injection of sub-LD50 (35 micrograms Kg-1) of the neurotoxic fraction (F3) of the Egyptian cobra Naja haje on the plasma level of ACTH and serum levels of cortisol, insulin, glucose, total lipids, triacylglycerols, free fatty acids, total cholesterol, HDL and LDL-cholesterol, and glycogen content of liver and kidneys were studied in rabbit pretreated with cyproteron acetate (CA) or saline solution and propylene glycol (PG) to elucidate the possible role of the hypothalamo-pituitary adrenal (HPA) axis in the venom fraction-induced hyperglycemia. F3 increased cortisol and insulin level in both groups, whereas ACTH was found to decrease subsequent to the treatment. Serum glucose level was elevated by F3 treatment and this effect was substantiated in CA-treated rabbits. This hyperglycemia was concomitant with a decline in glycogen content of the liver and kidneys. A decline in serum total lipids, triacylglycerols, and free fatty acids was observed following F3 treatment, and this effect was intensified by CA-pretreatment. These data suggest that F3 stimulates glucocorticoid release from adrenocortical cells which, in turn, may modulate both insulin and glucose turnover to maintain hyperglycemia during stress period. The possible underlying mechanisms were discussed.