Synergistic Effect of Thymoquinone and Interferon Alpha on Immunological Dysfunctions and Oxidative Damage in γ- irradiated Rats

Abstract

The objective of this study is to give more information about the role of thymoquinone (TQ) as an antioxidant and interferon alpha (IFN-α) as an immune- modulator in radiation-protection. Irradiation was performed as a whole body exposure of rats to 4Gy of γ- irradiation every two weeks up to a total dose of 8Gy. Irradiated rats received 5mgTQ/Kg/body weight, daily and injected subcutaneously with 10,000 IU IFN-α / for 3 times per week for 28 days. The results showed that animals exposed to γ- radiation had dramatic changes of all parameters including hematological alterations revealed by a decreased red blood corpuscles count, platelets count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), hematocrit and hemoglobin content and a severe depletion of white blood cells, lymphocytes, neutrophils and monocytes counts. Severe antioxidant enzymes depletion was also demonstrated and increased lipid peroxidation, in addition to deterioration in liver enzymes and renal dysfunction expressed by increased urea and creatinine. Hyperlipidemia was demonstrated by increased total cholesterol (TC), low-lipoprotein (LDL-C), and

triglycerides (TG) and decreased high-lipoprotein (HDL-

C).

Moreover, immune dysfunction was revealed by the increase of pro-inflammatory cytokines levels and depletion of spleen macrophages, T-cytotoxic and helper cells, and increased cells arrested in sub G0/1 and G2/M phase. Interestingly, rats exposed to γ-radiation exhibited increased exhaustion of T lymphocytes via down-regulation of Bcl-2 expression and up-regulation of programmed death receptor (PD-1), Bax, and caspase-3 expression, which sensitized these cells to apoptosis.