en عمومى General پژوهشي Research <p style="text-align:justify"><span style="font-size:12px;"><span style="font-family:Tahoma;"><b><span style="color:#2d73b4">Background: </span></b>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.<br> <b><span style="color:#2d73b4">Methods: </span></b>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.<br> <b><span style="color:#2d73b4">Results: </span></b>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.<br> <b><span style="color:#2d73b4"><span style="letter-spacing:-.1pt">Conclusion: </span></span></b>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.</span></span><br> &nbsp;</p> AMP-Activated Protein Kinases, Dorsomorphin, Drug-Induced Liver Injury, Fluoxetine, Metformin 182 188 http://ijt.arakmu.ac.ir/browse.php?a_code=A-10-1374-1&slc_lang=en&sid=1 Amin Hasanvand dr.hasanvand@yaahoo.com 100319475328460018844 100319475328460018844 No Hepatitis Research Center, Department of Physiology and Pharmacology, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran. Peyman Astaraki peymanastaraki@yahoo.com 100319475328460018845 100319475328460018845 No Department of Internal Medicine, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran. Shakiba Shamsinia shakiba.shamsiniya@gmail.com 100319475328460018846 0009-0006-9594-9228 No Student Research Committee, Lorestan University of Medical Sciences, Khorramabad, Iran. Mohammadjavad Nourmohammadi mohammadjavad328@gmail.com 100319475328460018847 100319475328460018847 No Student Research Committee, Lorestan University of Medical Sciences, Khorramabad, Iran Fatemeh Hatami hatamifatemeh158@gmail.com 100319475328460018848 0009-0003-9397-4014 No Student Research Committee, Lorestan University of Medical Sciences, Khorramabad, Iran. Mehdi Birjandi mehdibirjandi@gmail.com 100319475328460018849 100319475328460018849 No Department of Biostatistics, School of Health and Nutrition, Lorestan University of Medical Sciences, Khorramabad, Iran. Zahra Haghighatian haghighatian14@yahoo.com 100319475328460018850 100319475328460018850 No Department of Pathology, School of Medicine, Lorestan University of Medical Science, Khorramabad, Iran. Peyman Amanolahi Baharvand amanolahi1984@yahoo.com 100319475328460018851 100319475328460018851 No Department of English, School of Medicine, AJA University of Medical Sciences, Tehran, Iran. Nader Rahimi nrahimi@razi.tums.ac.ir 100319475328460018852 100319475328460018852 Yes Health and Environment Research Center, Ilam University of Medical Sciences, Ilam, Iran.