Immunomodulatory effect of new quinolone derivative against cisplatin/gamma radiation-induced renal and brain toxicity in mice

Treatment of cancer often requires exposure to radiation, which has several limitations involving non-specific toxicity toward normal cells, reducing the efficacy of treatment. Recent studies synthesize new quinolone derivatives to satisfy other purposes such as treatment of inflammatory and malignant diseases. The main purpose of the present study is to evaluate the effect of a new quinolone derivative; 2-(1-Ethyl-4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl)-2-oxoacetic acid (EHQA) and its possible mechanism against gamma radiation (IRR) and cisplatin (Cis) induced nephrotoxicity and neurotoxicity in mice. The structure of the newly synthesized quinolone derivative was elucidated by microanalytical and spectral data, which were found consistent with the assigned structures. Exposure to Cis and IRR significantly induced renal damage manifested by a significant increase in levels of urea and creatinine. Moreover, the exposure to both Cis and IRR significantly decreased the levels of anti-apoptotic protein; Bcl-2 in both renal and brain tissue homogenate accompanied by activation of an inflammatory marker; IL-17. Immunophenoting results showed an activation of T- lymphocytes marker; CD3 and B-lymphocytes marker; CD19. Interperitonial administration of EHQA significantly ameliorated the above-mentioned parameters. Overall, the present results indicated that EHQA is a promising anti-inflammatory and anti-apoptotic agent. From the obtained results it can be concluded that EHQA could be a candidate as immunomodulatory agents. Further studies are required to establish its molecular mechanism.