Radioprotective effects of hesperidin on oxidative damages and histopathological changes induced by X-irradiation in rats heart tissue

Abstract

This study was carried out to evaluate radioprotective effects of hesperidin (HES) administration before the irradiation on the cardiac oxidative stress and histopathological changes in an experimental rat model. The cardiovascular complications of radiation exposure cause morbidity and mortality in patients who received radiotherapy. HES, an antioxidant flavonoid found in citrus fruits, suggests the protection against the tissue damage. Fifty-eight rats were divided into four groups: Group 1 received phosphate buffered saline (PBS) and sham radiation; Group 2, HES and sham radiation; Group 3, PBS and radiation; and Group 4, HES and radiation. The rats were exposed to single dose of 18 Gy of 6 MV X-ray. One hundred milligrams per kilogram doses of HES was administered for 7 days before irradiation. The estimation of superoxide dismutase (SOD), malondialdehyde (MDA), and histopathological analyses was performed at 24 h and 8 weeks after radiation exposure. The irradiation of chest area resulted in an elevated MDA level and decreased SOD activity. Moreover, long-term pathological lesions of radiation were inflammation, fibrosis, the increased number of mast cells and macrophages, and development of plaque, vascular leakage, myocardial degeneration, and myocyte necrosis. Although the administration of HES decreases inflammation, fibrosis, mast cell and macrophage numbers, and myocyte necrosis, it did not result in reduced thrombus, myocardium degeneration, and vascular leakage. In conclusion, these results suggest that HES can perform a radioprotection action. The protective effect of HES may be attributable to its immunomodulatory effects and free radical-scavenging properties.

Keywords: Cardiomyopathy; cardiotoxicity; hesperidin; radioprotector.

Figure 1

Dose-dependent effect of hesperidin on the survival rate of rats observed for an experimental duration of 60 days. Control group: Six rats survived; radiation group: Five rats survived; hesperidin + R group: Eight rats survived

Figure 2

Histopathological findings of rat hearts in the acute phase (24 h). H and E stains of hearts taken at ×400 from unirradiated (a and b) and irradiated (c and d) rats reveal mild inflammation and the scattered foci of inflammatory cell in a subpopulation of the irradiated rats. The flashes indicate the accumulation of lymphocyte, macrophages, and inflammation in heart tissue. (a): Control, (b): Hesperidin, (c): Radiation, (d): Hesperidin + R

Figure 3

Histopathological findings of rat hearts in the chronic phase (8 weeks). H and E stains of hearts were taken at x400. Myocardial tissue and vascular bed are seen normal (a and f). Acute inflammation and accumulation of inflammatory cells (b), atheroma plaque associated with intraplaque angiogenesis and macrophage infiltration (c), cardiac myocyte necrosis (d) in the myocardial tissue are observed. Mild inflammation and the decreased infiltration of inflammatory cells are also discerned (e). (a): Control, (b-d): Radiation, (e and f): Hesperidin + R

Figure 4

Histopathological findings of rat hearts in the chronic phase (8 weeks). Masson's trichrome stains of hearts were taken at ×100 and collagen deposition as an indicator of fibrosis is seen light blue. Myocardial tissue and vascular bed are considered normal (a). Acute collagen deposition is distinguished in the epicardial (b), endocardial (c) and myocardial (d) layers of ventricle. In addition, mild collagen deposition is detected in the endocardial (e) and myocardial (f). (a): Control, (b-d): Radiation, (e and f): Hesperidin + R

Figure 5

Histopathological findings of rat hearts in the chronic phase (8 weeks). Acid fast stains of hearts were taken at ×400 magnification and mast cells seem dark blue points. Normal appearance is observed in the myocardium at the control group (a). Mast cell infiltration appears minimal to moderate at the epicardial (b) and endocardial (e) of the ventricle. Acute mast cells infiltration is recognized in the myocardial (d) and endocardial (c) layers of ventricle. (f) Myocardial tissue is characterized by mild infiltration of mast cells. (a): Control, (b-d): Radiation, (e and f): Hesperidin + R