The current study was designed to estimate the effect of υ-radiation on male rats pretreated with Levetiracetam (LEV) and/or Oxcarbazepine (OXC). Poly-treatment of rats with LEV, OXC and υ-radiation showed a significant elevation in the activity of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and isoenzyme creatinine kinase-MB (CK-MB) along with, an increase in the level of creatinine, urea, cardiac troponin (cTnI) and glutamate. These increases were associated with a decrease in acetylcholine (Ach) and υ-aminobutyric acid (GABA) levels. The data further revealed a significant increase of the apoptotic mediators tumor necrosis factor alpha (TNF-α) and brain caspase3 as well as, alterations in the oxidative stress parameters. The Results of the histopathological examination of liver, kidney, heart and brain tissues indicated coincidence with those recorded by the biochemical analysis. It seems promising to conclude that the exposure to υ-radiation intensified the deleterious and detrimental effect of dual treatment of LEV and OXC in rats.

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