Protective Effect of Thymoquinone Against Fluoxetine-Induced Liver Damage Through Enhancing Antioxidant and Anti-Inflammatory System in Male Rats

Fluoxetine is a drug used to treat depression and has toxic effects on liver cells. Thymoquinone, the most important active ingredient in black seed (Nigella sativa), has several pharmacological effects, including sedation, reduced motor activity, and muscle relaxation. This study aimed to investigate the effect of thymoquinone on reducing the hepatotoxicity effects of fluoxetine.

A total of forty Wistar rats were treated with fluoxetine, thymoquinone, and silymarin for four weeks. Different techniques, including biochemical analysis, qRT-PCR, and histopathological examination, were performed to investigate the effect of drugs on the oxidant/antioxidant system and inflammatory responses.

Our results revealed that fluoxetine increased lipid peroxidation and protein oxidation and inhibited antioxidant systems in rat hepatocytes. In addition, fluoxetine increased the expression of the proinflammatory cytokine TNF-α and also the migration of lymphocytes to liver cells. In contrast, thymoquinone (10, 20, and 40 mg/kg) significantly decreased MDA, PC, and TNF-α levels. Moreover, thymoquinone enhanced the catalytic activity of antioxidant enzymes, including catalase, superoxide dismutase, glutathione peroxidase, and GSH. Thymoquinone only at a dose of 40 mg/kg can inhibit the infiltration of lymphocytes into the liver.

Thymoquinone exerted liver protective effects against fluoxetine hepatotoxicity by inducing antioxidant and antiinflammatory activities. This study suggests that thymoquinone, in combination with fluoxetine, can be used to reduce liver damage.