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Egypt. J. Exp. Biol. (Zoo.). 2013; 9(1): 141-150


GENOTOXIC AND MOLECULAR STUDIES ON CYCLOSPORINE A- AZITHROMYCINE INTERACTION AND THE PROTECTIVE EFFECT OF GARLIC DURING ADMINISTRATION

Amany Abd El-monem Tohamy Warda A. Khalifa Manal F. El Khadragy Adel K. Ibrahim.

Abstract
The experiment was conducted to study the effects of both Cyclosporine A- (CsA) and Azithromycine (AZM), and to demonstrate the interaction of combination of CsA with AZM and the protective properties of garlic against each drug of them, besides Cyclosporine - Azithromycine interaction. The study was planned to clarify changes in chromosomal aberrations (CsA), expression of tumor necrosis factor alpha (TNF-α) and biochemical changes in different organs of Male Sprague-Dawley rats during period of oral administration of drug or drugs. The alterations after oral administration of animals with doses equal to 25 mg/kg of CsA, 500 mg/kg of AZM and 300 mg/kg of garlic were estimated after one and seven days. Non significant changes were observed in all types of structural and numerical chromosomal aberrations after one day of oral administration of the used drugs. After seven days of oral administration of CsA alone, CsA + garlic, CsA + AZM, and CsA + AZM + garlic, a significant increase in structural and numerical chromosomal aberrations were noticed. No significant changes in structural and numerical CAs were noticed after seven days of oral administration of AZM or AZM + garlic. The mean values of TNF-α gene expression, when measured with real time PCR assay, revealed that its expression in the three control groups were higher than the groups received the drug alone, in case of AZM and AZM+ CSA, while the group received CSA alone was the lowest group in TNF-α expression. Biochemical results showed significant changes in serum AST, ALT, GGT, LDH, ALP, globulin, BUN, creatinine and glucose after oral administration of CsA. In conclusion, CsA was genotoxic on chromosomes and TNF-α gene, AZM administration alone or with CsA showed safety protection and minimal interaction while garlic may improve the hazard effect of CsA.

Key words: Cyclosporine A, Azithromycine, Garlic, Genotoxicity, TNF-α expression, Biochemical changes



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