Cryogenic role of central endogenous hydrogen sulfide in the rat model of endotoxic shock

Abstract Thermoregulatory responses to lipopolysaccharide (LPS) are affected by modulators that increase (propyretic) or decrease (cryogenic) body temperature (Tb). We tested the hypothesis that central hydrogen sulfide (H 2 S) acts as a thermoregulatory modulator and that H 2 S production in the anteroventral preoptic region of the hypothalamus (AVPO) is increased during hypothermia and decreased during fever induced by bacterial lipopolysaccharide (LPS, 2.5 mg/kg i.p.) in rats kept at an ambient temperature of 25 °C. Deep Tb was recorded before and after pharmacological inhibition of the enzyme cystathionine β-synthase (CBS – responsible for H 2 S endogenous production in the brain) combined or not with LPS administration. To further investigate the mechanisms responsible for these thermoregulatory adjustments, we also measured prostaglandin D 2 (PGD 2 ) production in the AVPO. LPS caused typical hypothermia followed by fever. Levels of AVPO H 2 S were significantly increased during hypothermia when compared to both euthermic and febrile rats. Intracerebroventricular (icv) microinjection of aminooxyacetate (AOA, a CBS inhibitor; 100 pmol) neither affected Tb nor basal PGD 2 production during euthermia. In LPS-treated rats, AOA caused increased Tb values during hypothermia, along with enhanced PGD 2 production. We conclude that the gaseous messenger H 2 S modulates hypothermia during endotoxic shock, acting as a cryogenic molecule.