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Impact of Diclofenac Sodium on Tilmicosin-Induced Acute Cardiotoxicity in Rats (Tilmicosin and Diclofenac Cardiotoxicity)

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Abstract

To assess the influence of diclofenac sodium (DIC) treatment on tilmicosin (TIL) prompted cardiotoxicity, forty albino rats were randomly divided into four equal groups: control, TIL group (single subcutaneous injection of 75 mg/kg BW tilmicosin phosphate 30%), TIL + DIC group (single subcutaneous injection of tilmicosin phosphate 30% and then injection intramuscularly of 13.5 mg/kg BW/day for 6 days diclofenac sodium) and DIC group (intramuscular injection of 13.5 mg/kg BW/day diclofenac sodium for 6 days). Creatine kinase-MB, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, urea and creatinine significantly elevated in all treated groups, but markedly in TIL + DIC group serum. Lipid peroxidation significantly increased, and reduced glutathione significantly decreased in tissues of all groups. Several histopathological alterations were noticed in heart, liver, kidneys and lungs of all treated groups, particularly TIL + DIC group. Ultrastructurally, myocardium of TIL and TIL + DIC groups showed characteristic changes for myocardial apoptosis and degeneration. Significant differences were detected in area percentage of caspase-3 protein expression and bcl-2 immunoreactivity in cardiomyocytes, particularly in TIL + DIC group. This study is the first to indicate that one of the possible mechanisms of TIL cardiotoxicity is myocardial apoptosis. DIC amplifies TIL-induced cardiotoxicity besides its hepato-nephrotoxicity.

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Acknowledgements

We would thank Professor Dr. Mahmoud M. A. Elmaghraby for accomplishing the statistical analysis.

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Authors and Affiliations

  1. Department of Pathology, Faculty of Veterinary Medicine, Alexandria University, P.O. Box. 22758, Edfina-Rashid-Behera, Egypt

    Samah S. Oda

  2. Department of Histology and Cytology, Faculty of Veterinary Medicine, Alexandria University, P.O. Box. 22758, Edfina-Rashid-Behera, Egypt

    Amira E. Derbalah

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Correspondence to Samah S. Oda.

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Oda, S.S., Derbalah, A.E. Impact of Diclofenac Sodium on Tilmicosin-Induced Acute Cardiotoxicity in Rats (Tilmicosin and Diclofenac Cardiotoxicity). Cardiovasc Toxicol 18, 63–75 (2018). https://doi.org/10.1007/s12012-017-9414-2

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