Fluoxetine attenuates hepatic ischemia-reperfusion injury through antioxidant, anti-inflammatory and anti-apoptotic mechanisms.

Authors

Musab Işık, Gülderen Şahin, Gülnaz Kervancıoğlu, Muhittin Onur Yaman, Nermin Yelmen, İbrahim Güner

Published in

Naunyn-Schmiedeberg's archives of pharmacology. Jun 19, 2026. Epub Jun 19, 2026.

Abstract

Hepatic ischemia-reperfusion injury is a major clinical problem associated with liver surgery, trauma, and transplantation, characterized by oxidative stress, inflammation, microcirculatory dysfunction, and apoptosis. Fluoxetine, a selective serotonin reuptake inhibitor, has been reported to exert antioxidant, anti-inflammatory, and antiapoptotic effects. The present study aimed to investigate the potential protective effects of fluoxetine against experimental hepatic ischemia-reperfusion injury in rats. Male Wistar rats were randomly assigned to three groups: control, ischemia-reperfusion and fluoxetine-treated ischemia-reperfusion (n = 7 each). Hepatic ischemia-reperfusion injury was induced by infrarenal abdominal aortic cross-clamping for 60 min followed by 120 min of reperfusion. Fluoxetine (20 mg/kg/day, intraperitoneal) was administered for three consecutive days prior to ischemia. Oxidative stress markers, antioxidant parameters, inflammatory and anti-inflammatory cytokines, apoptotic markers, and specific tissue injury biomarkers were measured in liver homogenates using ELISA. Histopathological alterations were evaluated by light microscopy. Ischemia-reperfusion significantly increased oxidant markers, inflammatory cytokines, NF-κB activation, apoptotic indices, liver enzyme levels, and histological damage, while reducing antioxidant capacity. Fluoxetine treatment markedly restored antioxidant defenses, suppressed oxidative stress, inflammation, apoptosis, and microcirculatory injury, and significantly improved histopathological findings compared with the untreated ischemia-reperfusion group. Fluoxetine exerts a protective effect against hepatic ischemia-reperfusion injury through antioxidant, anti-inflammatory and antiapoptotic mechanisms, suggesting its potential as a therapeutic agent in conditions associated with hepatic ischemia-reperfusion.

PMID:
42319415
Bibliographic data and abstract were imported from PubMed on 19 Jun 2026.

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