org . americanscience . www :// http ) 12 ( 6 ; 2010 , Journal of American Science org . americanscience . www :// http 865 org . americanscience @ editor Radioprotective activity of L- Carnitine and α -Lipoic acid against whole body γ- irradiation in rats Sally S. Alam 1* , Aziza M. Hassan 1 , Nermine K. El Halawaney 1 , Dalia E. El-Nashar 2 , Mona G. Abd El-Azeem 2 1 Cell Biology Department, National Research Center, 12622 Dokki, Giza, Egypt. 2 Health Radiation Research, National Center for Radiation Research and Technology (NCRRT). Atomic Energy Authority, Cairo, Egypt. dr_Sallyalam@yahoo.com Abstract: The present study was designed to investigate the radioprotective efficacy of naturally occurring antioxidants, L - carnitine (LC) and α -Lipoic acid (LA) on radiation-induced bone marrow and liver damages in a rat model. The cellular changes were estimated by evaluation the expression of antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GPx), genes using RT-PCR and DNA damage in bone marrow and liver cells. The histopathological and ultra structural changes were also determined. To evaluate the effects of the above antioxidants, adult rats were treated with LC (300 mg/kg b wt) and LA (150 mg/kg b wt) after exposure to whole-body γ-rays (6 Gy) for 10 days, or treated with LC & LA for 7 consecutive days and one hour after the last administration, animals irradiated a single dose of whole-body γ-rays (6 Gy) and received again LC & LA in same dose for 10 days. The obtained data revealed that γ –irradiation significantly decreases the expression of SOD and GPx genes and increases DNA fragmentation in liver cells as well as the incident of micronuclei in bone marrow cells. In addition, different histological and ultra structural alterations in the liver of irradiated animals were recorded. These alterations were varied from hemorrhage, congestion in blood vessels, pyknosis and necrosis as well as complete degenerated area in the liver electron micrographs recorded swollen mitochondria, fragmented endoplasmic reticulum, distorted nuclei and cell membrane. Treatment with LC & LA post-exposure to radiation attenuated most of these changes. Whereas pre- and post- treatment with LC & LA to γ-irradiation normalized the expression of the antioxidant genes enzymes, decreased the DNA fragmentation and micronuclei formation with a normal restoration of histopathologial and ultra structure liver architecture. Thus, our results suggested that pre- treatment with LC & LA offers protection against γ-irradiation induced cellular damage. [Sally S. Alam, Aziza M. Hassan, Nermine K. El Halawaney, Dalia E. El-Nashar, Mona G. Abd El-Azeem. Radioprotective activity of L- Carnitine and α -Lipoic acid against whole body γ- irradiation in rats. Journal of American Science 2010; 6(12):865-879]. (ISSN: 1545-1003). http://www.americanscience.org. Keywords: L-Carnitine, α-Lipoic acid, γ-irradiation, DNA fragmentation, Antioxidant gene expression, Ultra structure, Histopathology. 1. Introduction Ionizing radiation (IR) is an important environmental risk factor for various cancers and also a major therapeutic agent for cancer treatment. Radiation toxicity occurs either by direct attack on the genetic material and/or by generating reactive oxygen species (ROS) by radiolysis of water. It also attenuates the endogenous antioxidant enzymes which are considered as first line defense mechanism to maintain redox balance and normal biochemical processes (Parihar et al., 2007). Consequently, the organs become more susceptible to the deleterious effects of ROS that attack various cellular components including DNA, RNA, proteins and membrane lipids, thereby leading to significant cellular damage (Tominaga et al., 2004). The potential application of radioprotective chemicals in the event of planned exposures or radiation accidents/incidents has been investigated from the beginning of the nuclear era (Weiss and Simic, 1988). It has also been considered possible that radiation therapy for cancer patients could be improved by the use of radioprotectors to protect normal tissue. They include sulfhydryl compounds, antioxidants, plant extracts, immunomodulators, and other agents (Nair et al., 2001). α-Lipoic acid (LA), a naturally occurring sulphydryl compound found in virtually all plants and animal species that functions as a coenzyme in pyruvate dehydrogenase and α-ketoglutarate dehydrogenase mitochondrial reactions, leading to the production of cellular energy. In human body LA