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 (α-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, α-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.

Red grape juice protects the rat thyroid gland against hypercholesterolemic changes. Ultrastructural and biochemical evidences.

OBJECTIVES: This study aimed to assess the impact of high cholesterol diet (HCD)-induced hypercholesterolemia on the rat thyroid gland and investigate the role of grape juice (GJ) in reducing such impact through biochemical and histopathological methods. MATERIALS AND METHODS: Thirty male Wistar rats sorted into three groups (the control, HCD-fed group, and the HCD+GJ fed group for 13 weeks) were used in this study. Lipid profile, blood glucose and insulin, thyroid hormones, some oxidants/antioxidants parameters were assessed. After the end of the experiment, thyroid glands were dissected out and processed for histopathological assessment using the light and electron microscopy. RESULTS: Based on the lipid profile, HCD induced hypercholesterolemia in rats after 13 weeks. This resulted in significant (p<0.001) increase of the levels of insulin, blood glucose, thyroid-stimulating hormone (TSH) (596.4±17 IU∕mL), thyroxine (T4) (202.8±14.1 ng∕mL) and malondialdehyde (MDA) (21.2±4.9 nmol∕mg protein), while the levels of triiodothyronine (T3) (12.6±1.9 ng∕mL) and total antioxidant capacity (TAOC) (21.2±4.9 U∕mg protein) decreased in HCD-fed rats compared to that of the controls. Structurally, thyroid gland follicles of HCD-fed rats showed cytoplasmic vacuolation, stratification and increased thickness of some lining cells. Ultrastructurally, some of follicular and parafollicular cells showed heterochromatic nuclei, degenerated mitochondria, intracytoplasmic lipid droplets and deposition of collagen fibers between the follicles. GJ could improve the lipid and antioxidants profiles, reduced blood glucose level, thyroid hormones, and alleviated the HCD-induced structural changes in the thyroid. CONCLUSIONS: GJ administrated simultaneously with HCD ameliorated the negative impact of the function and structure of the thyroid.