| First Author | Nakashima MA | Year | 2019 |
| Journal | Cytokine | Volume | 121 |
| Pages | 154734 | PubMed ID | 31151047 |
| Mgi Jnum | J:295862 | Mgi Id | MGI:6455237 |
| Doi | 10.1016/j.cyto.2019.154734 | Citation | Nakashima MA, et al. (2019) Chronic ethanol consumption increases reactive oxygen species generation and the synthesis of pro-inflammatory proteins in the heart through TNFR1-dependent mechanisms. Cytokine 121:154734 |
| abstractText | We evaluated the role of tumor necrosis factor (TNF)-alpha receptor 1 (TNFR1) on ethanol-induced cardiac dysfunction. Male C57BL/6J wild-type (WT) or TNFR1-deficient mice (TNFR1(-/-)) were treated with ethanol (20% v/v) for 10weeks. Increased protein expression of TNFR1 and NFkappaB p65 was detected in the left ventricle (LV) of WT mice chronically treated with ethanol. Echocardiographic analysis showed that ethanol consumption increased left ventricular posterior wall end-diastolic diameter and left ventricular posterior wall end-systolic diameter in WT, but not TNFR1(-/-) mice. Increased levels of TNF-alpha, interleukin (IL)-6, superoxide anion (O2(-)), thiobarbituric acid reactive substances (TBARS) as well as increased nitrotyrosine immunostaining were detected in the LV from WT, but not TNFR1(-/-) mice. Conversely, treatment with ethanol decreased nitrate/nitrite (NOx) concentration in the LV. Histopathological analysis showed that ethanol did not induce inflammatory infiltrates, necrosis or edema in the LV. No differences in the ventricular expression of iNOS, Nox2 or COX-2 as well as in the activity of superoxide dismutase (SOD), myeloperoxidase (MPO) and N-acetyl-beta-D-glucosaminidase (NAG) were found after treatment with ethanol. Our study provided novel evidence that ethanol consumption augmented the production of reactive oxygen species (ROS) and the synthesis of pro-inflammatory proteins in the LV through TNFR1-dependent mechanisms. These findings provided novel mechanistic insights about the contribution of TNFR1 in the initial steps of the cardiac damage induced by ethanol. |
