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Role of hydrogen sulfide during septic shock hypothermia


Hydrogen sulfide (H2S) has been recently appointed as an important endogenous gas acting during systemic inflammation. In animal models of systemic inflammation, H2S basal levels are altered in the preoptic area of the hypothalamus (POA) in response to the administration of endotoxin (bacterial lipopolysaccharide, LPS). Furthermore, we demonstrated that H2S in POA modulates the febrile response induced by LPS. It seems probable, therefore, the involvement of H2S in the POA, and more specifically in the medial nucleus of the POA (MPO), as well as a modulator of hypothermia, a response that appears in place of fever during severe forms of systemic inflammation, i.e., when a high dose of LPS is administered, leading to endotoxemic shock. The hypothesis to be tested in this proposal is therefore that H2S regulates endogenous pre-optical response of hypothermia during endotoxemic shock, modulating the synthesis of prostanoid cryogenic, prostaglandin (PG) D2. Our specific goals are therefore to investigate (i) whether endogenous H2S in the POA region modulates the response of hypothermia, (ii) if the DP for PGD2 receptors in the POA region participate in this response, (iii) during the hypothermia the basal levels of MPO on H2 and PGD2 are altered, and (iv) the endogenous H2S hypothermia pre-modulates the optical PGD2 synthesis of the MPO. Conducting this study build a scenario of paramount importance to the field of knowledge in which the project is inserted, revealing that the bioavailability of an endogenous gaseous molecule (H2S) in the POA is able to regulate the response of hypothermia during endotoxemic shock by modulating the synthesis of PGD2 in MPO. In addition, we may also assess the if the cryogenic effect of endogenous PGD2 depends on its interaction with its receptor PD pre-optic in non-infectious animal model of severe systemic inflammation. (AU)

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(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DONATTI, ALBERTO F.; ARAUJO, REBECA M.; SORIANO, RENATO N.; AZEVEDO, LEOPOLDO U.; LEITE-PANISSI, CHRISTIE A.; BRANCO, LUIZ G. S.. Role of hydrogen sulfide in the formalin-induced orofacial pain in rats. European Journal of Pharmacology, v. 738, p. 49-56, . (12/13888-7, 12/01417-0, 13/12850-9)

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