دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: The Therapeutic Value of Hydralazine in Reducing Inflammatory Response, Oxidative Stress, and Mortality in Animal Sepsis: Involvement of the PI3K/AKT Pathway.
المؤلفون: 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.
المصدر: Shock (Augusta, Ga.) [Shock] 2021 Nov 01; Vol. 56 (5), pp. 782-792.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 9421564 Publication Model: Print Cited Medium: Internet ISSN: 1540-0514 (Electronic) Linking ISSN: 10732322 NLM ISO Abbreviation: Shock Subsets: MEDLINE
أسماء مطبوعة: Publication: 2002- : Philadelphia : Lippincott Williams & Wilkins
Original Publication: Augusta, GA : BioMedical Press, [1994-
مواضيع طبية MeSH: Hydralazine/*pharmacology , Hydralazine/*therapeutic use , Inflammation/*drug therapy , Oxidative Stress/*drug effects , Phosphatidylinositol 3-Kinases/*physiology , Proto-Oncogene Proteins c-akt/*physiology , Sepsis/*drug therapy , Sepsis/*mortality, Animals ; Rats ; Rats, Wistar ; Signal Transduction
مستخلص: 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.)
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المشرفين على المادة: 26NAK24LS8 (Hydralazine)
EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
تواريخ الأحداث: Date Created: 20210208 Date Completed: 20220324 Latest Revision: 20230824
رمز التحديث: 20231215
DOI: 10.1097/SHK.0000000000001746
PMID: 33555842
قاعدة البيانات: MEDLINE
الوصف
تدمد:1540-0514
DOI:10.1097/SHK.0000000000001746