Abstract
Alcohol use disorder (AUD) is a public health problem characterized by a marked increment in systemic inflammation. In the last few years, it has been described as the role of alcohol in neuroinflammation affecting some aspects of neuronal function. Interestingly, inflammation is reduced with fenofibrate treatment, a PPARα agonist used to treat dyslipidemia. On the other hand, alcohol has been associated with chronic inflammation and fibrosis in the lungs, affecting their normal function and increasing respiratory infections. However, a deep characterization of the role of alcohol in the worsening of chronic respiratory diseases has not been described completely. In this work, we present a novel study using rats treated with alcohol and fenofibrate to evaluate the relevant features of chronic respiratory disease: inflammation, mucus hypersecretion, and fibrosis. The analysis of extracted lungs showed an increment in the inflammatory infiltrates and pro-inflammatory cytokine levels associated with alcohol. Interestingly, the treatment with fenofibrate decreased the expression of these markers and the infiltrates observed in the lungs. The levels of mucin Muc5ac showed an increment in animals treated with alcohol. However, this increment was markedly reduced if animals were subsequently treated with fenofibrate. Finally, we documented an increment of collagen deposition around airways in the animals treated with alcohol compared with control animals. However, fenofibrate treatment reduced this deposition to a level similar to the control animals. These results showed the role of alcohol in the increment of pathological features in the lungs. Moreover, these features were attenuated due to the fibrate treatment, which allows us to glimpse this drug's promising role as lung anti-inflammatory therapy.