Thymoquinone Preserves Pancreatic Islets Structure Through Upregulation of Pancreatic β-Catenin in Hypothyroid Rats

Abstract

Background: Altered status of thyroid hormones, which have a key role in regulating metabolism, was reported to affect glucose homeostasis and insulin secretion.

Objective: This study was designed to assess the impact of propylthiouracil (PTU)-induced hypothyroidism on the pancreatic islet cells and the efficacy of thymoquinone (TQ) in alleviating this impact and explore the mechanism behind it alleviating oxidative stress and affecting β-catenin expression.

Materials and methods: PTU (6 mg/kg/body weight) was used to induce hypothyroidism in Wistar rats. Four groups of rats (n=6 each) were utilized in this study. Untreated hypothyroid and TQ-treated hypothyroid groups (50 mg/kg/body weight for 4 weeks) were included. Thyroid functions, antioxidant profile and pancreatic β-catenin and IL-10 mRNA were measured. Histopathological and immunohistochemical assessment of the pancreas was performed.

Results: PTU administration induced a hypothyroid status that was associated with a marked disturbed oxidant/antioxidant status and a significant hyperglycemia (p<0:001), hypoinsulinemia (p=0.01) and decreased HOMA-β-cell (p<0.001). Islet cells of hypothyroid pancreas showed many degenerative changes with increased apoptosis, reduced insulin β-catenin immunoexpression. Administration of TQ alleviated these effects on the thyroid function, antioxidants, structure of pancreatic islet cells. Up-regulation of β-catenin, IL-10 and CAT gene expression in pancreatic islets after treatment with TQ supported its antioxidant and preserving β-cell function and viability mechanistic action.

Conclusion: TQ alleviated PTU-induced hypothyroidism changes in insulin homeostasis and pancreatic β cells mostly through its antioxidant effect as well as up-regulation of pancreatic β-catenin expression.

Keywords: Nigella sativa; caspase-3; glucose; hypothyroidism; insulin; pancreas.

Figure 1

Effect of Thymoquinone on serum level of T3 (A), T4 (B), TSH (C), fasting insulin (D) and glucose (E), HOMA-IR and HOMA-β (F). *Significantly different compared to the control group (p<0.05). ^#Significantly different compared to the Hypothyroid group (p<0.05).

Figure 2

Effect of Thymoquinone on serum level of MDA (A), NO (B) and antioxidant activities of catalase (CAT) (C), Glutathione peroxidase (GPX) (D), reduced glutathione (GSH) (E) and superoxide dismutase (SOD) (F). *Significantly different compared to the control group (p<0.05). ^#Significantly different compared to the Hypothyroid group (p<0.05).

Figure 3

Effect of Thymoquinone on gene expression of catalase (A), β-catenin (B) and IL-10 (C) in pancreatic islets of Langerhans. *Significantly different compared to the control group (p<0.05). ^#Significantly different compared to the hypothyroid group (p<0.05).

Figure 4

Effect of Thymoquinone on histological structure of the pancreatic islets of Langerhans (A–D) as well as immunoexpression of insulin (E–H), caspase-3 (I–L) and β-catenin (M–P) expression in the pancreas of the studied groups. Haematoxylin and eosin-stained section showed islets (IS) between the pancreatic acini (AC). Islet cells (arrow) appear intact in control, TQ and hypothyroid+TQ groups while they appear degenerated in Hypothyroid group. Note the presence of blood capillaries (thick arrow). Qualitative assessment of the morphometric measurements and immunoexpression (Q–T) was done using image Pro Plus image analysis software version 6.0. *Significantly different compared to the control group (p<0.05). ^#Significantly different compared to the Hypothyroid group (p<0.05).

Figure 5

A diagram summarized the proposed mechanism of antihyperglycemic effect of thymoquinone in hypothyroid model. Catalase (CAT) (C), glutathione peroxidase (GPX) (D), reduced glutathione (GSH) (E) and superoxide dismutase (SOD), T regulatory cells (Tregs).