Chronic ethanol consumption and sepsis cause oxidative stress and renal dysfunction. This study aimed to examine whether chronic ethanol consumption sensitizes the mice 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, plasma creatinine, oxidative stress and inflammatory parameters, iNOS, cytokines, metalloproteinases (MMPs) and theirs tissue inhibitors (TIMPs) were evaluated. Chronic ethanol consumption increased SBP, creatinine levels, O<sub>2</sub><sup>.</sup><sup>−</sup> and H<sub>2</sub>O<sub>2</sub> levels, lipid peroxidation, catalase activity, Nox4, IL-6 and TNF-α levels, and MMP-9/TIMP-1 ratio. SL-CLP decreased SBP, increased creatinine levels, 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 O<sub>2</sub><sup>.</sup><sup>−</sup>, 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.
Reconstitution of the microsomal ethanol-oxidizing system. Qualitative and quantitative changes of cytochrome P-450 after chronic ethanol consumption.