Chronic ethanol consumption increases vascular oxidative stress and the mortality induced by sub-lethal sepsis: Potential role of iNOS

Author(s)

Ceron, Carla S. ^{[1, 2]} ; do Vale, Gabriel T. ^{[3, 1]} ; Simplicio, Janaina A. ^{[3, 1]} ; Ricci, Sthefany T. ^[1] ; De Martinis, Bruno S. ^[4] ; de Freitas, Andressa ^[5] ; Tirapelli, Carlos R. ^[1]

Affiliation

^[1] Univ Sao Paulo, Escola Enfermagem Ribeirao Preto, DEPCH, Lab Farmacol, Ribeirao Preto, SP - Brazil

^[2] Univ Fed Alfenas, Fac Ciencias Farmaceut, Alfenas, MG - Brazil

^[3] Univ Sao Paulo, Fac Med Ribeirao Preto, Programa Posgrad Farmacol, Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Quim, Ribeirao Preto, SP - Brazil

^[5] Univ Estadual Londrina, Dept Ciencias Fisiol, Londrina, PR - Brazil

• Document type: Journal article
• Source: European Journal of Pharmacology; v. 825, p. 39-47, APR 15 2018.
• Web of Science Citations: 3

Abstract

We hypothesized that long-term ethanol consumption would increase the mortality and aggravate the deleterious effects of sub-lethal cecal ligation and puncture (SL-CLP) in the vasculature by inducing the expression of inducible nitric oxide (NO) synthase (iNOS). Male C57BL/6J wild-type (WT) or iNOS-deficient mice (iNOS(-/-)) were treated with ethanol (20% v/v) for 12 weeks and then subjected to SL-CLP. Mice were killed 24 h post-operatively or followed six days for survival. Septic ethanol-treated mice showed a higher mortality than septic WT mice. However, septic iNOS-deficient mice treated with ethanol showed a decreased mortality rate when compared to ethanol-treated WT mice. Ethanol and SL-CLP augmented superoxide anion (O-2(-)) generation in the mesenteric arterial bed (MAB) of both WT and iNOS-deficient mice. Treatment with ethanol and SL-CLP enhanced lipoperoxidation in the MAB of WT, but not iNOS-deficient mice. SL-CLP enhanced nitrate/nitrite (NOx) concentrations in the MAB of WT, but not iNOS-deficient mice. Both, ethanol and SL-CLP increased TNF-alpha and IL-6 levels in the MAB. Treatment with ethanol as well as SL-CLP up-regulated the expression of iNOS in the MAB of WT mice. The major finding of our study is that chronic ethanol consumption increases the mortality induced by SL-CLP and that iNOS plays a role in such response. Although ethanol led to vascular alterations, it did not aggravate the vascular injury induced by SL-CLP. Finally, iNOS mediated the increase in oxidative stress and pro-inflammatory cytokines induced by SL-CLP in the vasculature. (AU)

• FAPESP's process: 15/22046-8 - Role of AT1 receptors on ethanol withdrawal-induced hypertension and vascular oxidative stress
• Grantee: Carlos Renato Tirapelli
• Support Opportunities: Regular Research Grants