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.

Ameliorating Effect of Ashwagandha (Withania Somnifera) Extract on Hippocampus and Growth Plate Changes Associated With Propylthiouracil Induced Hypothyroidism in Juvenile Rats

“…The statistical analysis revealed a considerable drop in the serum T3 and T4 concentrations; also, the TSH showed a significant rise in comparison to the control values. The current findings were in agreement with a number of studies (26,30). The theory underlying the PTU action mechanism is based on the fact that the thyroid peroxidase enzyme regulates T4 production, which in turn restricts thyroid hormone release and the conversion of T3 and T4 into their active forms in peripheral tissues (31 and 32).…”

“…Rats in the PTU-group were given 6 mg/kg/day of (26) propylthiouracil orally. Rats in PTU+Ash group received oral doses of both propylthiouracil (6 mg/kg/day) (26) and ashwagandha extract (Ash) (50 mg/kg/day) (27). For a total of 30 days, the therapies were administered orally while using a gastric tube.…”

Propolis versus Nigella sativa Oil challenging the apoptotic pathway in Propylthiouracil-induced Hypothyroidism on parotid gland

“…In the present work, the hypothyroid status was achieved by administration of propylthiouracil (PTU) for 6 weeks and its establishment was con rmed by a decrease in serum level of T3 and T4 and an increase in TSH level (Faddladdeen et al, 2021).…”

Possible Protective Effect of Fish Oil on Parotid Salivary Glands in Adult Male Albino Rats With Ptu - Induced Hypothyrodism (Histological and Ultrastructural Study)

“…In the present study, PTU was used to induce hypothyroidism in rats, which was serologically monitored. This drug was used in previous studies to induce an animal model of hypothyroidism (23) . It was reported that PTU blocks the production of newly secreted thyroid hormone in the thyroid gland.…”