Baicalin provides protection against fluoxetine-induced hepatotoxicity by modulation of oxidative stress and inflammation

BACKGROUND Fluoxetine is one of the most widely prescribed anti-depressant drugs belonging to the category of selective serotonin reuptake inhibitors.Long-term fluoxetine treatment results in hepatotoxicity.Baicalin,a natural compound obtained from the Chinese herb Scutellaria baicalensis is known to have antioxidant,hepatoprotective and anti-inflammatory effects.However,the beneficial effects of baicalin against fluoxetine-induced hepatic damage have not previously been reported.AIM To evaluate the protective action of baicalin in fluoxetine-induced liver toxicity and inflammation.METHODS Male albino Wistar rats were divided into seven groups.Group 1 was the normal control.Oral fluoxetine was administered at 10 mg/kg body weight to groups 2,3,4 and 5.In addition,groups 3 and 4 were also co-administered oral baicalin(50 mg/kg and 100 mg/kg,respectively)while group 5 received silymarin(100 mg/kg),a standard hepatoprotective compound for comparison.Groups 6 and 7 were used as a positive control for baicalin(100 mg/kg)and silymarin(100 mg/kg),respectively.All treatments were carried out for 28 d.After sacrifice of the rats,biomarkers of oxidative stress[superoxide dismutase(SOD),catalase(CAT),reduced glutathione(GSH),glutathione-S-transferase(GST),advanced oxidation protein products(AOPP),malondialdehyde(MDA)],and liver injury[alanine transaminase(ALT),aspartate transaminase(AST),alkaline phosphatase(ALP),total protein,albumin,bilirubin]were studied in serum and tissue using standard protocols and diagnostic kits.Inflammatory markers[tumor necrosis factor(TNF-α),interleukin(IL)-6,IL-10 and interferon(IFN)-γ]in serum were evaluated using ELISA-based kits.The effect of baicalin on liver was also analyzed by histopathological examination of tissue sections.RESULTS Fluoxetine-treated rats showed elevated levels of the serum liver function markers(total bilirubin,ALT,AST,and ALP)and inflammatory markers(TNF-α,IL-6,IL-10 and IFN-γ),with a decline in total protein and albumin levels.Biochemical markers of oxidative stress such as SOD,CAT,GST,GSH,MDA and AOPP in the liver tissue homogenate were also altered indicating a surge in reactive oxygen species leading to oxidative damage.Histological examination of liver tissue also showed degeneration of hepatocytes.Concurrent administration of baicalin(50 and 100 mg/kg)restored the biomarkers of oxidative stress,inflammation and hepatic damage in serum as well as in liver tissues to near normal levels.CONCLUSION These findings suggested that long-term treatment with fluoxetine leads to oxidative stress via the formation of free radicals that consequently cause inflammation and liver damage.Concurrent treatment with baicalin alleviated fluoxetine-induced hepatotoxicity and liver injury by regulating oxidative stress and inflammation.