Effects of methylene blue and α-lipoic acid on body temperature and fever in pigeons

Abstract

The effects of oxygen radical scavenger methylene blue and thiol-reductant α-lipoic acid on diurnal core temperature (Tc) changes and on fever were assessed in pigeons (Columba livia) in an ambient temperature of 26±1°C, with lights on at 09:00 and off at 21:00. Intravenous (iv) injection of 10 μg/kg Escherichia coli lipopolysaccharide (LPS) at 13:00 evoked after a 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 to values which were 0.48±0.10°C higher than control between 05:00 and 06:00. The diurnal fever pattern of Tc was not altered when injections of LPS were applied to the same animals in intervals of 7 days. The iv infusion of 5 mg/kg/h methylene blue lasting from 12:00 to 18:00 did not alter the diurnal rise of Tc during the light phase, but attenuated the decrease of Tc during the dark phase. The initial decrease of Tc was not affected when LPS was injected during infusion of methylene blue; however, methylene blue completely prevented the febrile rise of Tc. 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 levels not significantly different from the afebrile state between 18:00 and 20:00. The results suggest that an increased production of reactive oxygen species following LPS mediates the febrile rise of Tc because fever is prevented by the oxygen radical scavenger methylene blue. 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.