The Therapeutic Value of Hydralazine in Reducing Inflammatory Response, Oxidative Stress, and Mortality in Animal Sepsis: Involvement of the PI3K/AKT Pathway.

Autor:	Santos DMD; Health Sciences Graduate Program - Universidade Federal de Sergipe, Aracaju, SE, Brazil.; Department of Physiology - Universidade Federal de Sergipe, São Cristóvão, SE, Brazil., Da Silva EAP; Department of Physiology - Universidade Federal de Sergipe, São Cristóvão, SE, Brazil., Oliveira JYS; Department of Physiology - Universidade Federal de Sergipe, São Cristóvão, SE, Brazil., Marinho YYM; Department of Physiology - Universidade Federal de Sergipe, São Cristóvão, SE, Brazil., Santana IR; Department of Physiology - Universidade Federal de Sergipe, São Cristóvão, SE, Brazil., Heimfarth L; Department of Physiology - Universidade Federal de Sergipe, São Cristóvão, SE, Brazil., Pereira EWM; Department of Physiology - Universidade Federal de Sergipe, São Cristóvão, SE, Brazil., Júnior LJQ; Health Sciences Graduate Program - Universidade Federal de Sergipe, Aracaju, SE, Brazil.; Department of Physiology - Universidade Federal de Sergipe, São Cristóvão, SE, Brazil., Assreuy J; Department of Pharmacology, Universidade Federal de Santa Catarina, Florianopolis, SC, Brazil., Menezes IAC; Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, PR, Brazil., Santos MRVD; Health Sciences Graduate Program - Universidade Federal de Sergipe, Aracaju, SE, Brazil.; Department of Physiology - Universidade Federal de Sergipe, São Cristóvão, SE, Brazil.
Jazyk:	angličtina
Zdroj:	Shock (Augusta, Ga.) [Shock] 2021 Nov 01; Vol. 56 (5), pp. 782-792.
DOI:	10.1097/SHK.0000000000001746
Abstrakt:	Abstract: Sepsis is an amplified systemic immune-inflammatory response produced by a microorganism, which involves activation of inflammatory cytokine signaling pathways and oxidative stress. A variety of studies have shown that hydralazine (HDZ) has potent antioxidant and anti-inflammatory proprieties. Therefore, we hypothesize that HDZ can improve the clinical outcome of sepsis. Thus, this work aimed to evaluate therapeutic value of HDZ in reducing inflammatory response, oxidative stress, and mortality in animal sepsis, and to investigate its possible mechanism of action. Sepsis was induced by the cecal ligation and puncture (CLP) method in Wistar rats. After surgery, the animals were randomly divided into three groups: sham, sepsis, and sepsis + HDZ (1 mg/kg, s.c.). All groups were monitored for 48 h to assess survival rate, and clinical, hemodynamic, biochemical, and cellular parameters. After euthanasia, blood, spleen, liver, and kidneys were collected for analysis. Blood serum cytokines, tissue myeloperoxidase (MPO) activity, and oxidative stress parameters were assessed. Involvement of the PI3K/Akt pathway was also investigated. Sepsis was successfully induced by the CLP technique. HDZ treatment increased the survival rate (from 50% to 90%), improved glycemia control, reduced the clinical severity sepsis and mean arterial pressure; and prevented increased MPO activity, TNF-α, IL-1β, IL-10 levels, and oxidative damage markers. Additionally, HDZ significantly prevented the increase of Akt activation in the liver and kidney. HDZ largely mitigated the effects of sepsis by suppressing inflammatory and antioxidant responses via the PI3K/Akt pathway. These findings provide evidence that HDZ can be a new therapeutic alternative for treating sepsis. Competing Interests: The authors report no conflicts of interest. (Copyright © 2021 by the Shock Society.)
Databáze:	MEDLINE
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