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Mechanisms underlying the hepatoprotective effect of silymarin on fluoxetine-induced liver injury in rats: the implication of peroxisome proliferator–activated receptor-gamma (PPAR-γ)

Abstract

Fluoxetine (FLX) is used widely as a first-line treatment in cases of depression and other neuropsychiatric disorders. Although its safety has been approved, the use of FLX was associated with liver injury and chronic liver disease. Silymarin (SIL) possesses antioxidant and anti-inflammatory effects. Hence, this study aimed to evaluate the protective effects of SIL on FLX-induced liver damage, implying the role of peroxisome proliferator-activated receptor-gamma (PPAR-γ). Rats were randomized to four groups: control group, SIL group (100 mg/kg/day; orally), FLX group (10 mg/kg/ day; orally), and SIL + FLX group. FLX-induced liver damage was evidenced through elevated liver function biomarkers and induced hepatic histopathological changes. Concurrent SIL treatment resulted in a significant decrease in hepatotoxicity biomarkers and histopathological alterations. FLX induced oxidative stress and inflammation attenuated by SIL. In addition, SIL up-regulated PPAR-γ expression. FLX elevated Bcl-2- associated X protein (Bax) mRNA expression and decreased B-cell lymphoma 2 (Bcl2) mRNA expression, an effect markedly reversed by SIL. SIL possesses ameliorative effects against FLX-induced liver injury in rats. This effect may be due to attenuation of oxidative stress and inflammation and upregulation of PPAR-γ expression.

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Correspondence to Gellan Alaa Mohamed Kamel.

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Mohamed Kamel, G.A., Harahsheh, E. & Hussein, S. Mechanisms underlying the hepatoprotective effect of silymarin on fluoxetine-induced liver injury in rats: the implication of peroxisome proliferator–activated receptor-gamma (PPAR-γ). Comp Clin Pathol 31, 689–698 (2022). https://doi.org/10.1007/s00580-022-03369-7

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  • DOI: https://doi.org/10.1007/s00580-022-03369-7

Keywords

  • Liver damage
  • Fluoxetine, Silymarin
  • Oxidative stress
  • Inflammation
  • Peroxisome proliferator-activated receptor-gamma, Nuclear factor (PPAR-γ)