ANTAGONISTIC EFFECT OF ASCORBATE ON ETHANOL-INDUCED HYPOTHERMIA IN THE RAT

To evaluate the effects of ascorbic acid on ethanol-induced hypothermi a, male rats of the Sprague-Dawley strain (200-250 g) were treated wit h a hypothermic (2.0 g/kg ip) dose of ethanol, with and without pretre atments with graded doses of ascorbic acid (pH 2.3, 4.0 or 6.8, 500-10 00 mg/kg ip) or sodium ascorbate (apparent pH 6.8, 562-1125 mg/kg ip) solutions, and the body temperatures were monitored for 3 hr. Ethanol caused a significant drop in body temperature, which was maximal at 60 min postdosing, and which did not return to preethanol values for the remaining of the observation period. A solution of ascorbic acid at a pK 2.3 was hypothermic in itself, and when given as a pretreatment it accentuated the hypothermic response to ethanol. In doses > 500 mg/kg , both ascorbic acid (pH 4.0 or 6.8) and sodium ascorbate attenuated t he thermolytic effect of ethanol and accelerated the return of the bod y temperatures to pretreatment values in a dose-related manner. Sodium ascorbate caused a significant (p < 0.05) reduction in the blood etha nol levels and an enhancement of the blood and liver acetaldehyde leve ls that followed a hypothermic dose of ethanol. The same pretreatment did not influence the blood ethanol levels of rats on a nonhypothermic (1 g/kg ip) dose of ethanol to a significant extent. Furthermore, asc orbate offered a marked protection against the hypothermia due to the cyanamide-ethanol reaction. These results suggest that the protective effects of ascorbate are related to its ability to stimulate blood eth anol clearance through increased metabolism.