Histopathological and immunohistochemical alterations in rat heart after thyroidectomy and the role of hemin and ketoconazole in treatment

The heart is a major target organ for thyroid hormone action and marked changes occur in cardiac function in the case of hypo- or hyperthyroidism. Also, thyroid hormone has a significant regulatory effect on the rate of heme oxidation in the liver. Heme oxygenase (HO) is a heme-catabolizing enzyme that converts heme into biliverdin, iron and carbon monoxide. HO−1 and its reaction products protect the heart and vasculature in pathological conditions. We studied the changes in the heart structure of thyroidectomized rat at the post-pubertal stage, in addition to the role of hemin as HO inducer and ketoconazole (KTZ) as HO inhibitor in treatment. 35 male Wistar rats were equally divided into seven groups; the first and second groups were the control and Sham-operated groups respectively while the 3rd and 4th groups were subjected to sham operation then treated with hemin (G3) and KTZ (G4). The 5th group (G5) was thyroidectomized group. The 6th and 7th groups were subjected to thyroidectomy then treated with hemin (G5) and KTZ (G6) respectively. Serum T3 & TSH levels in thyroidectomized rats were significantly decreased and increased respectively when compared with the control group. Left ventricle section in the heart of thyroidectomized rats showed many of abnormalities as hydrophobic changes of myofibrillar structure with striations, myocardial atrophy and edema, focal haemorrhage when compared with that in control and sham groups. The iNOS label index was significantly decreased in thyroidectomized rat heart (grade 1) and their levels were significantly increased in treated thyroidectomized rats with hemin and KTZ (grades 3 & 2 respectively) when compared with control and sham rat groups (grade 4). Treatment of thyroidectomized rat with hemin improves the histopathological alternation and the intensity of iNOS immunoreactive cells demonstrating the recovery of some injury.