Thymoquinone reverses nonalcoholic fatty liver disease (NAFLD) associated with experimental hypothyroidism

Objectives: To assess the efficacy of thymoquinone (TQ), the most active constituent in Nigella sativa, which is a medicinal plant from the Ranunculaceae family, in restoring the normal liver structure after 6-propyl-2-thiouracil (PTU)-induced hypothyroidism and explore the mechanism behind this. Materials and Methods: Hypothyroidism was induced in rats by injection of PTU [6 mg/kg body weight (b.w.)] for six weeks. Twenty-four adult male Wistar rats were divided into four groups; the control, TQ-treated at the dose 400 mg/kg b.w., untreated hypothyroidism and TQ-treated hypothyroid groups. Serum levels of thyroid hormones and antioxidant profile were measured. Real-time polymerase chain reaction was used to assess gene expression of catalase (CAT). Liver was histopathologically examined using routine and immunohistochemical techniques. Results: Livers of rats with hypothyroidism displayed nonalcoholic fatty liver disease (NAFLD) in the form of steatosis as well as nonalcoholic steatohepatitis (NASH). Moreover, there was an intralobular inflammatory reaction associated with significant (p<0.05) increases in the density of resident hepatic macrophages [cluster of differentiation 68 (CD68)(+) cells], as well as in activated hepatic stellate cells, alpha-smooth muscle actin (alpha-SMA) index in livers with hypothyroidism. Resolution of hypothyroid NAFLD was observed in livers after treatment with TQ. The significantly increased (p<0.05) steatosis, lobular inflammation, NAFLD activity scores, a-SMA index as well as CD68(+) cells induced by hypothyroidism were corrected after TQ administration. Up-regulation of the CAT gene in livers with hypothyroidism after treatment with TQ supported our hypothesis of its antioxidant mechanistic hepatoprotective action. Conclusions: TQ efficiently restores the normal liver histology in hypothyroid rats with up-regulation of the antioxidant CAT gene.