الفهرس | Only 14 pages are availabe for public view |
Abstract Daily oral administration of Dimethyl fumarate (DMF), Empagliflozin (EMPA), or Telmisartan (TEL) to alcohol fed mice, significantly reduced serum levels of ALT, AST, and ALP. They also reversed the increased total and differential cell count recovered in BALF. Moreover, they showed anti-oxidant activity by increasing the activities of SOD and GSH with concomitant reduction of MDA and NO in liver and lung homogenate. Furthermore, they inhibited the release of proinflammatory cytokines, including TNF-𝛼, IL-1β, and IL-6, via the downregulation of NF-𝜅B. These results were associated with an amelioration of histopathology. The protective effect of DMF, EMPA, or TEL, i.e., against oxidative stress and inflammation, was associated with the up-regulation of PPAR-γ, Nrf-2, and of their target gene, Hmox-1. In conclusion, our results demonstrated that DMF, EMPA, or TEL modulated alcohol-induced liver and lung injury by suppressing oxidative stress and inflammatory responses via the activation of Nrf-2/PPAR-γ crosstalk and inhibition of NF-κB. The present study provided a potential basis for future clinical research and treatment of alcohol-induced organ dysfunction. Also, it reports extra protective mechanisms of these drugs unrelated to its known pharmacological effects, which can be used to explore more of their pleiotropic effects. |