Abstract
The effect of thiol-reductant α-lipoic acid on diurnal temperature (Tc) changes and fever was assessed in pigeons (Columba livia) in ambient temperature of 26 ± 1°C, with lights on at 09:00 and off at 21:00. Intravenous (iv) injection of 10 μg/kg E. coli lipopolysaccharide (LPS) at 13:00 evoked after latency of 30 min first a variable decrease of Tc, followed by an increase starting 90 min later towards values which were 0.78 ± 0.04°C higher than control between 18:00 and 20:00. Tc decreased in the dark phase parallel to the decline of Tc of afebrile pigeons but with a flatter slope. Iv injections of 12.5, 25.0 and 37.5 mg/kg α-lipoic acid at 16:00 lowered Tc dose-dependently by 0.75 ± 0.09°C, 1.47 ± 0.14°C, and 1.90 ± 0.18°C, respectively, the hypothermic effects lasting 50, 90 or 140 min, respectively. Treatment with the non-competitive glutamate N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine maleate (MK801) blocked the α-lipoic acid-induced hypothermia. Injection of 25 mg/kg α-lipoic acid 3 h after LPS caused a decrease of Tc by 1.05 ± 0.20°C, lasting about 60 min. Tc then returned to level not significantly different from the afebrile state between 18:00 and 20:00. The hypothermic action of α-lipoic acid is assumed to be induced by reduction of vicinal thiol groups of the NMDA receptor, because the hypothermic effect is blocked by NMDA receptor antagonist MK801. The data support the hypothesis that the NMDA receptor is involved in thermoregulation of birds and that augmented oxidation of vicinal thiol groups attached to its ion channel leads to hyperthermia or causes fever. [J Physiol Sci. 2006;56 Suppl:S228]
