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

摘要

The effects of oxygen radical scavenger methylene blue and thiol-reductant alpha-lipoic acid on diurnal core temperature (Tc) changes and on fever were assessed in pigeons (Columba livia) in an ambient temperature of 26 +/- 1degreesC, with lights on at 09:00 and off at 21:00. Intrivenous (iv) injection of 10 mug/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 +/- 0.04degreesC 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+/-0.10degreesC higher than control' between 05:00 and 06:00. The diumal fever pattern of Tc was not altered when injections of LPS were applied to the same animals in intervals of 7 day. 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 then LPS was injected during infusion of methylene blue; however, methylene blue completely prevented the febrile r se of Tc. Iv injections of 12.5, 25.0 and 37.5 mg/kg alpha-lipoic acid at 16:00 lowered Tc dose-dependently by 0.75+/-0.09degreesC, 1.47+/-0.14degreesC, and 1.90+/-0.18degreesC, respectively, the hypothermic effects lasting 50, 90 or 140min, respectively. Treatm.nt with the non-competitive glutamate N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine maleate (MK801) blocked the alpha-lipoic acid-induced hypothermia. Injection of 25 mg/kg alpha-lipoic acid 3h after LPS caused a decrease of Tc by 1.05+/-0.20degreesC, lasting about 60min. Tc then returned to levels not significantly different from the aft brile 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 alpha-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 ittached to its ion channel leads to hyperthermia or causes fever.