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

Autor(es)

do Valle, Gabriel Tavares ^[1] ; Ricci, Sthefany Teodoro ^[1] ; Silva, Alessandra Oliveira ^[2] ; Tirapelli, Carlos Renato ^[1] ; Ceron, Carla Speroni ^{[2, 3]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Escola Enfermagem Ribeirao Preto EERP, Sao Paulo, SP - Brazil

^[2] Univ Fed Alfenas UNIFAL MG, Dept Alimentos & Medicamentos, Alfenas, MG - Brazil

^[3] Univ Fed Ouro Preto UFOP, Dept Ciencias Biol, Ouro Preto, MG - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Canadian Journal of Physiology and Pharmacology; v. 99, n. 7, p. 699-707, JUL 2021.
• Citações Web of Science: 0

Resumo

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, O-2(center dot-), H2O2, lipid peroxidation, catalase activity, Nox4, IL-6, and TNF-alpha levels, and MMP-9/TIMP-1 ratio. SL-CLP decreased SBP, increased creatinine, lipid peroxidation, IL-6, TNF-alpha, 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 O-2(-), lipid peroxidation, IL-6, TNF-a, 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. (AU)

• Processo FAPESP: 15/22046-8 - Participação dos receptores AT1 no aumento da pressão arterial e do estresse oxidativo vascular induzidos pela abstinência ao etanol
• Beneficiário: Carlos Renato Tirapelli
• Modalidade de apoio: Auxílio à Pesquisa - Regular