Concerted effects of L-carnitine and vitamin E on cardio-pulmonary apoptosis induced by gamma irradiation in rats

Abstract

Pulmonary fibrosis and cardiotoxicity are a common and dose-limiting side-effect of ionizing radiation used to treat cancers of the thoracic region. This study aims at investigating the role of Bcl-2, Bax protein and caspase-3 in the pathogenesis of tissue damage induced by gamma irradiation (IRR) and the protective potential role of vitamin E (Vit E) and/or L-carnitine (L-car) against γ-irradiation induced oxidative injury. Irradiation was performed as a whole body γ-irradiation (5Gy). Immnuohistochemistry was used to estimate Bcl-2 expression. The level of Bax and caspase 3 activity were determined using enzyme-linked immunosorbent assay. C-reactive protein was determined using immunoturbidimetric assay. Results revealed that γ-irradiation (5Gy) induced apoptosis via the mitochondrial pathway by downregulating Bcl-2 expression, upregulating Bax protein and activating caspase-3. Administration of Vit E (50mg/kg) and/or L-car (300mg/kg) prior to gamma-irradiation decreased apoptosis through changing the expression of Bcl-2, Bax and caspase-3 activity. Exposure to γ-irradiation increased triglyceride, cholesterol, low density lipoprotein-cholesterol (LDL-C), C-reactive protein (CRP) and potassium levels, creatine kinase (CK-MB) and lactate dehydrogenase (LDH) activities and decreased high density lipoprotein-cholesterol (HDL-C) levels. The altered lipid profile, CRP and potassium levels, CK-MB and LDH activities induced by exposure to γ-irradiation were significantly renovated in Vit E and/or L-car pretreated γ-irradiated rats. In conclusion, Vit E and/or L-car might ameliorate γ-irradiation induced apoptosis via modulation of Bcl-2, Bax and caspase-3.