EFFECT OF HESPERIDIN ON AMIDORONE INDUCED PULMONARY TOXICITY AND POSSIBILITY OF RECOVERY AFTER WITHDRAWAL OF AMIODARONE IN ALBINO RAT (HISTOLOGICAL, IMMUNOHISTOCHEMICAL AND ULTRASTRUCTURAL STUDY) Marwa Salah1 and Mona A.A. Arafa2 Zoology Department, Faculty of Science, Beni-Suef University1 Anatomy Department, Faculty of Medicine for Girls, Alazhar University2
Amiodarone (AM) was known as an anti-arrhythmic drug that was used to help keep the heart beating normally in people with life-threatening heart rhythm disorders of the ventricles (tachycardia or fibrillation). It had some serious side effects, including pulmonary toxicity. Hesperidin was a naturally occurring bioflavonoid, a compound in plants with antioxidant properties. The aim of this work was to study the possible protective effect of Hesperidin on AM induced pulmonary toxicity and also to detect the possibility of recovery after withdrawal of AM. Forty five adult male albino rats were used and divided into five groups. Group I rats served as control. Group II rats were given hesperidin orally at 100 mg/kg daily for 12 weeks. Group III rats were given AM orally at 30 mg/kg daily for 12 weeks. Group IV rats were given hesperidin concomitantly with AM in the same previous doses, by the same route and for the same duration. Group V rats received the same dose of AM for 12 weeks, then were left for 6 weeks without any treatment (withdrawal group). The rats of the first four groups were sacrificed after 12 weeks while the rats of the fifth group were sacrificed after 18 weeks. The lungs were dissected and processed for histological, immunohistochemical and ultrastructural study. Light microscopic examination of lung tissue after administration of AM revealed severe distortion of its architecture in the form of collapsed alveoli and markedly thickened interalveolar septa with congested blood capillaries and focal cellular infiltrations. Also, some bronchioles showed cellular debris in their lumena and cellular infiltration of their smooth muscle layer reaching the epithelial lining. Results obtained by electron microscope examination revealed that pneumocytes type I and II had electron-dense nuclei. Pneumocytes type I showed vacuolated cytoplasm while pneumocytes type II showed degenerative changes of their lamellar bodies leaving irregular empty spaces. Congested blood capillaries, fibroblast cells and extensive interstitial collagen fibers deposition were also seen. In addition the interalveolar septa showed cellular infiltration by eosinophils and neutrophils. Moreover, immuonohistochemical staining with PCNA revealed increased number of brown deposits in the nuclei of the alveolar cell lining. Co-administration of hesperidin with AM showed obvious preservation of the lung architecture; however, a mild improvement in the lung injury was observed in animals after AM withdrawal. Conclusion: Concomitant administration of hesperidin with AM in rat had effectively protected the lung tissue against the severe damage induced by AM.