Ethanol consumption increases renal dysfunction and mortality in a mice model of sub-lethal sepsis

Author:

do Valle Gabriel Tavares1,Ricci Sthefany Teodoro1,Silva Alessandra Oliveira2,Tirapelli Carlos Renato1,Ceron Carla Speroni23

Affiliation:

1. Escola de Enfermagem de Ribeirão Preto (EERP), Universidade de São Paulo -USP, São Paulo, Brasil.

2. Departamento de Alimentos e Medicamentos, Universidade Federal de Alfenas (UNIFAL-MG), Minas Gerais, Brasil.

3. Departamento de Ciências Biológicas, Universidade Federal de Ouro Preto (UFOP), Minas Gerais, Brasil.

Abstract

Chronic ethanol consumption and sepsis cause oxidative stress and renal dysfunction. This study aimed to examine whether chronic ethanol consumption sensitizes the mouse kidney to sub-lethal cecal ligation and puncture (SL-CLP) sepsis, leading to impairment of renal function by tissue oxidative and inflammatory damage. Male C57BL/6J mice were treated for 9 weeks with ethanol (20%, v/v) before SL-CLP was induced. Systolic blood pressure (SBP), survival rate, creatinine plasma, oxidative stress, and inflammatory parameters, inducible nitric oxide synthase (iNOS), cytokines, and metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) levels were evaluated. Chronic ethanol consumption increased SBP, plasma creatinine, O2.−, H2O2, lipid peroxidation, catalase activity, Nox4, IL-6, and TNF-α levels, and MMP-9/TIMP-1 ratio. SL-CLP decreased SBP, increased creatinine, lipid peroxidation, IL-6, TNF-α, nitrate/nitrite (NOx), and iNOS levels, and MMP-2/TIMP-2 ratio, and decreased catalase activity. SL-CLP mice previously treated with ethanol showed a similar decrease in SBP but higher mortality and creatinine levels than SL-CLP alone. These responses were mediated by increased O2, lipid peroxidation, IL-6, TNF-α, NOx, iNOS, MMP-2, and MMP-9 levels, and MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios. Our findings demonstrated that previous oxidative stress and inflammatory damage caused by ethanol consumption sensitizes the kidney to SL-CLP injury, resulting in impaired kidney function and sepsis prognosis.

Publisher

Canadian Science Publishing

Subject

Physiology (medical),Pharmacology,General Medicine,Physiology

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