tilmicosin and Cardiotoxicity

The present study aimed to investigate the possible mitigating effect of L-carnitine (LC) and/or α-tocopherol (Vit. E) administration against tilmicosin (TIL)-induced cardiotoxicity in rats. Fifty-six male albino rats were divided into seven groups according to LC, Vit. E, and/or TIL administration. Control, LC, and Vit. E groups were given saline, 150 mg LC/kg body weight (BW)/day and 100 mg Vit. E/kg BW/day, respectively, orally once daily for 15 days. The TIL group was administered saline orally once daily for 15 days and a single dose of TIL (75 mg/kg BW) subcutaneously (SC) on day 14 from the starting of the experimental period (15 days). The TIL-LC, TIL-Vit. E, and TIL-LC-Vit. E groups received 150 mg LC/kg BW/day, 100 mg Vit. E/kg BW/day, and 150 mg LC/kg BW pulse 100 mg Vit. E/kg BW, respectively, orally once daily for 15 days with TIL as described above. The results revealed that the administration of TIL significantly (P ≤ 0.05) raised serum activities of heart injury indicators, lactate dehydrogenase (LDH), creatine kinase (CK), and CK-MB with substantial increase (P ≤ 0.05) in the cardiac contents of malondialdehyde (MDA) and decreased in antioxidants. The pathological changes appeared in the form of necrotic muscle fibers and massive inflammatory cellular infiltrations in the cardiac muscle and increased the caspase-3 immunohistochemical expression in the heart tissues as well. These changes were ameliorated by LC and/or Vit. E administration. In conclusion, supplementation of LC and/or Vit. E ameliorated the cardiotoxicity of the TIL SC injection in the rat.

Topics: Animals; Antioxidants; Cardiotoxicity; Carnitine; Male; Oxidative Stress; Rats; Tylosin; Vitamin E

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.

Topics: Animals; Apoptosis; Biomarkers; Cardiotoxicity; Caspase 3; Chemical and Drug Induced Liver Injury; Diclofenac; Disease Models, Animal; Heart Diseases; Kidney Diseases; Lipid Peroxidation; Male; Myocytes, Cardiac; Oxidative Stress; Proto-Oncogene Proteins c-bcl-2; Pulmonary Edema; Rats; Tylosin

Tilmicosin (TIL) is a long-acting macrolide antibiotic approved for the treatment of cattle with Bovine Respiratory Disease. However, overdose of TIL has been reported to induce cardiotoxicity. The purpose of our experiment was to evaluate the protective effects of Commiphora molmol (mirazid (MRZ); myrrh) and (or) ascorbic acid (AA) against TIL-induced cardiotoxicity in mice. MRZ and AA were orally administered using stomach gavage, either alone or in combination for 5 consecutive days, followed with a single TIL overdose. TIL overdose induced a significant increase in serum levels of cardiac damage biomarkers (AST, LDH, CK, CK-MB, and cTnT), as well as cardiac lipid peroxidation, but cardiac levels of antioxidant biomarkers (GSH, SOD, CAT, and TAC) were decreased. Both MRZ and AA tended to normalize the elevated serum levels of cardiac injury biomarkers. Furthermore, MRZ and AA reduced TIL-induced lipid peroxidation and oxidative stress parameters. MRZ and AA combined produced a synergistic cardioprotective effect. We conclude that myrrh and (or) vitamin C administration minimizes the toxic effects of TIL through their free-radical-scavenging and potent antioxidant activities.

Topics: Animals; Ascorbic Acid; Cardiotonic Agents; Cardiotoxicity; Commiphora; Drug Synergism; Lipid Peroxidation; Male; Mice; Myocardium; Oxidative Stress; Resins, Plant; Tylosin