EFFECTS OF NICOTINE AND CARBON-MONOXIDE ON TISSUE AND SYSTEMIC CHANGES IN RATS

Male rats were exposed to CO (100, 250, or 500 ppm) and/or injected ip at hourly intervals for 4 hr with a subconvulsive dose of nicotine (0.5 or 1.0 mg/kg) to determine systemic and tissue changes. Each agent alone induced only slight changes in blood glucose and lactic acid, and no change in plasma enzyme activities. Nicotine (1.0 mg/kg) plus CO (100-500 ppm) produced elevated blood glucose and lactic acid, and increased plasma aspartate aminotransferase activity. Plasma alanine aminotransferase activity was increased with 1.0 mg/kg nicotine and 500 ppm CO. Nicotine (1.0 mg/kg) induced hypothermia and a low incidence in neutral fat droplets in thigh muscles, whereas nicotine in conjunction with CO produced a slightly more pronounced hypothermia and a high incidence of neutral fat deposition in thigh muscles. Plasma corticosterone concentration was not consistently altered in any group. This study demonstrates that nicotine and CO, in combination, induce more profound systemic and tissue changes than either agent alone. These changes are probably caused by the direct action of catecholamines released by nicotine, and prolonged nicotine toxicity due to the inhibitory effects of CO on hepatic drug metabolism. © 1979.