hepatoprotective effects of the adenosine monophosphate-activated protein kinase signaling pathway in the fluoxetine-induced hepatotoxic model in rats

Background: drug-induced liver injuries (dilis) can have various clinical manifestations ranging from asymptomatic abnormal liver tests to symptomatic acute liver disease. several studies have indicated that fluoxetine can lead to hepatotoxicity and affect liver enzyme activity. metformin suppresses sterol regulatory element-binding transcription factor 1. it reduces lipogenesis and fat accumulation by activating the adenosine monophosphate-activated protein kinase (ampk), which can have a protective effect on the liver.methods: the present study investigated the role of the ampk signaling pathway induced by metformin in preventing fluoxetine-induced hepatotoxicity in rats. rats were randomly divided into four groups of five, including a control group, a fluoxetine-induced hepatotoxicity (flux) group, a flux + metformin group, and a flux + metformin + dorsomorphin group. hepatotoxicity was induced by fluoxetine, and then the serum-specific liver marker, oxidative markers, and histopathology were measured.results: the findings demonstrated that the activation of ampk by metformin increased antioxidative activity and decreased necrosis, edema, and inflammatory cells in the liver. however, the results of the fourth group indicated that dorsomorphin administration reduced the beneficial effects of metformin by inhibiting the ampk signaling pathway.conclusion: the findings suggest that a decrease in inflammation and inhibition of oxidative stress in the liver may mediate the ampk signaling pathway in fluoxetine-induced hepatotoxicity.