Therapeutic Potential of Nanocurcumin in Mitigating Duloxetine‐Induced Hepatic Damage: Biochemical and Histopathological Insights

Abstract

ABSTRACT Duloxetine, a serotonin‐norepinephrine reuptake inhibitor, commonly prescribed for depression and chronic pain, has been implicated in hepatotoxicity, primarily driven by oxidative stress and inflammatory responses. This has led to growing interest in naturally derived antioxidant compounds as potential protective strategies. The aim of this study was to evaluate the hepatoprotective potential of nanocurcumin against duloxetine‐induced liver injury in a controlled animal model. Male Wistar rats were divided into eight experimental groups, control, Solvent, curcumin 200 mg/kg, nanocurcumin 200 mg/kg, duloxetine 60 mg/kg, and treatment groups that simultaneously received duloxetine and nanocurcumin. Biochemical assays measured liver function enzymes (ALT, AST), oxidative stress markers (MDA, TOS), and antioxidant enzymes (SOD, GPx). Proinflammatory cytokine levels, TNF‐α were also measured and liver tissue was evaluated histologically. Duloxetine administration significantly increased liver enzymes, oxidative stress markers, and TNF‐α levels, along with histopathological evidence of liver injury. Concomitant treatment with nanocurcumin reduced these effects and attenuated these changes, as evidenced by normalization of biochemical indices, enhanced antioxidant defense, suppression of proinflammatory cytokines, and preservation of liver structure. Nanocurcumin exhibits potent hepatoprotective effects against duloxetine‐induced liver injury, likely through enhancement of antioxidant capacity and modulation of inflammatory responses. These findings support its potential as an adjunctive therapy to duloxetine to mitigate hepatic side effects.