Mineralocorticoid receptor antagonism partially prevents dysfunction of T cell maturation in rats chronically treated with ethanol

Ethanol consumption induces thymic atrophy and affects T cell maturation in the thymus. However, the mechanisms underlying such effects still need to be fully understood. We attempted to investigate the role of mineralocorticoid receptors (MR) on ethanol-induced thymic atrophy, T cell maturation dysfunction, and the role of oxidative stress in such responses. Male Wistar Hannover rats were treated with ethanol (20%; in volume ratio) and/or potassium canrenoate, an antagonist of MR (MRA; 30 mg/kg/day, gavage) for five weeks. Blockade of MR prevented ethanol-induced increases in the number of double-positive (CD4(+)CD8(+)), CD8(+) single-positive (CD4(-)CD8(+)), CD4(+) single-positive (CD4(+)CD8(-)), and Foxp3(+)CD4(+) (Treg) cells in the thymus. Ethanol increased NOX2-derived superoxide (O-2(center dot-)), lipoperoxidation, and superoxide dismutase (SOD) activity in the thymus. Pretreatment with the MRA fully prevented these responses. Apocynin, an antioxidant, prevented ethanol-induced increases in the number of double-positive and CD8(+) single-positive cells but failed to prevent the rise in the number of CD4(+) single-positive and Treg cells induced by ethanol. Apocynin, but not the MRA, prevented thymic atrophy induced by ethanol. Our findings provided novel evidence for the participation of MR in thymic dysfunction induced by ethanol consumption. Oxidative stress mediates the increase in double-positive and CD8(+) single-positive cells in response to MR activation, while positive regulation of CD4(+) single-positive and Treg cells is independent of oxidative stress. Oxidative stress is a significant mechanism of thymic atrophy associated with ethanol consumption, but this response is independent of MR activation.