Rojas Diego A, Coronado Krishna, Pérez-Reytor Diliana, Karahanian Eduardo
Instituto de Ciencias Biomédicas (ICB), Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago 8910132, Chile.
Research Center for the Development of Novel Therapeutic Alternatives for Alcohol Use Disorders, Santiago 8910132, Chile.
Int J Mol Sci. 2024 Nov 28;25(23):12814. doi: 10.3390/ijms252312814.
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.
酒精使用障碍（AUD）是一个以全身炎症显著增加为特征的公共卫生问题。在过去几年中，已经描述了酒精在神经炎症中影响神经元功能某些方面的作用。有趣的是，非诺贝特治疗可减轻炎症，非诺贝特是一种用于治疗血脂异常的PPARα激动剂。另一方面，酒精与肺部的慢性炎症和纤维化有关，影响其正常功能并增加呼吸道感染。然而，酒精在慢性呼吸道疾病恶化中作用的深入特征尚未完全描述。在这项工作中，我们进行了一项新的研究，使用酒精和非诺贝特处理的大鼠来评估慢性呼吸道疾病的相关特征：炎症、黏液分泌过多和纤维化。对取出的肺组织的分析显示，与酒精相关的炎性浸润和促炎细胞因子水平增加。有趣的是，非诺贝特治疗降低了这些标志物的表达以及在肺中观察到的浸润。黏蛋白Muc5ac的水平在酒精处理的动物中增加。然而，如果动物随后用非诺贝特治疗，这种增加会明显减少。最后，我们记录到与对照动物相比，酒精处理的动物气道周围胶原沉积增加。然而，非诺贝特治疗将这种沉积降低到与对照动物相似的水平。这些结果显示了酒精在肺部病理特征增加中的作用。此外，这些特征因贝特类药物治疗而减弱，这使我们能够瞥见这种药物作为肺部抗炎治疗的潜在作用。
