The Potential Role of Hesperidin to Ameliorate Endocrine and Exocrine Pancreatic Changes in an Experimentally-Induced Hypothyroidism Rat Model: a Functional and Histological Study

Introduction: Thyroid dysfunction adversely affect the pancreas. Hesperidin, a flavonoid, has been explored for treating
pancreatic disorders including diabetes and pancreatitis.
Objectives: Evaluation of possible protective effect of hesperidin on pathophysiological and structural pancreatic changes in
carbimazole-induced hypothyroidism rat model.
Material and Method: Thirty adult male albino rats were divided into 3 groups (I) control, (II) hypothyroid, (III) hypothyroid
hesperidin treated group. Finally, rats were sacrificed; blood samples were collected to measure the levels of serum amylase,
lipase, insulin and fasting blood glucose. Malondialdehyde (MDA) and antioxidant enzymes were measured in pancreatic
homogenate. Pancreatic tissues were used in the histological, electron microscopic, morphometric and immunohistochemical
studies for Bax and insulin proteins.
Results: Hypothyroid rats showed a significant decrease of serum amylase, lipase and pancreatic antioxidant enzymes
compared with control. There was a significant increase of fasting blood glucose, serum insulin, homeostatic model assessment
in hypothyroid rats compared with control. There were no significant statistical differences between MDA levels among all
groups. Hypothyroid group revealed fatty infiltration and eosinophilic material deposition in the pancreatic connective tissue
septa. Acinar cells showed small dark nuclei, increased basal basophilia, cytoplasmic vacuolation, degenerated mitochondria
and dilated rough endoplasmic reticulum. β-cells of pancreatic islets were densely packed with insulin granules. There was
a significant increase of insulin immune-expression and increased of Bax immunoreactivity. Hypothyroid group displayed
a significant decrease of zymogen granules and significant increase in collagen fibers deposition compared with control.
Hesperidin administration to hypothyroid rats significantly improved serum amylase, lipase and pancreatic antioxidant
enzymes levels, down regulated insulin and Bax immunoexpression. Zymogen granules were significantly increased and
collagen fibers were significantly decreased compared with hypothyroid group. Histological results were consistent with the
biochemical results.
Conclusion: Hesperidin treatment of hypothyroid rats reversed the associated functional and structural pancreatic changes via
antioxidant and antiapoptotic mechanisms.