Er, AyseTras, BunyaminCetin, GulDik, Burak2020-03-262020-03-2620141678-03451679-9216https://hdl.handle.net/20.500.12395/30583Background: Tilmicosin is widely used in veterinary medicine and its accidental overdose by injection may cause death via causing negative inotropy and positive chronotropy in both the treated animal and the veterinarian. In addition, there is no any antidote against to tilmicosin-caused death. Amiodarone blocks some channels in the heart, but it has much complex effect including vagotonic, bradycardic etc on the heart. Considering vagotonic and bradycardic effects of amiodarone, it has been hypothesised that amiodarone may prevent tilmicosin-caused death. The aim of this study was to determine the effect of amiodarone on the survival rate of rats in tilmicosin-caused lethal toxicity. Materials, Methods & Results: Twenty female Wistar rats (body weight: 288 +/- 33.8 g, age: 7-8 months) were used in this study. The study protocol was approved by the Ethical Committee. Rats received food and water ad libitum. The rats were divided into two groups containing 10 rats each. Rats in Group 1 were administered 360 mg/kg of tilmicosin in a single subcutaneous injection. Rats in Group 2 were administered 25 mg/kg of amiodarone via the tail vein at 8. min after the single subcutaneous injection of tilmicosin in a dose of 360 mg/kg. After the injections, deaths were recorded at 0, 2, 6, 10, 12 and 24 h. At the end of the 24-h period, survival/death ratio was analysed by the Chi-square test. The level of statistical significance was set at P < 0.05. The survival rate of Group 2 (40%) was statistically significantly (P < 0.025) higher than that of Group 1 (0.0%). In control group all rats died at 10 h after subcutaneously tilmicosin injection. In Group 2 were administered 25 mg/kg of amiodarone (intravenously) at 8 min after the single subcutaneous injection of tilmicosin in a dose of 360 mg/kg, and 2 rats died at 2 h and 4 rats died at 12 h. At the end of the experiment, all rats died in tilmicosin injected group whereas 4 rats lived in amiodarone and tilmicosin administered group. Clinically tilmicosin administered rats were observed as worse than amiodarone and tilmicosin administered group. Observed clinical signs of toxicity were fluffed feathers, ataxia, weakness in the legs, hypoactivity, lethargy. Discussion: Tilmicosin, a macrolide antibiotic, is widely used in the therapy of respiratory system infections in cattle and sheep. However, tilmicosin has cause serious cardiac side effects, and after tilmicosin administration to animals or accidental self-exposure of this drug to humans, if may cause heart related side effects including chest pain, increased serum cardiac damage markers, changed electrocardiogram, and decreased antioxidant enzyme activities in the heart, serum potassium level and death, as well as. Tilmicosin causes negative inotropy and positive chronotropy. Although the mechanism of tilmicosin-induced cardiotoxicity is not fully known, the inhibitory effect of tilmicosin on the entry of calcium into the cell may cause this lethal effect. It can be speculated that the beneficial effect of amiodarone in tilmicosin toxicity may primarily depend on the potassium channel blocking, antiarrhythmic effect and other exactly not explained effects. Amiodarone may increase survival rate and may be beneficial in the treatment of tilmicosin-caused lethal toxicity. However, especially specific cellular target or other effects of amiodarone on the heart are needed to determine in the tilmicosin toxicity.eninfo:eu-repo/semantics/closedAccesstilmicosinamiodaronecardiotoxicArticle42Q4WOS:000339158400001Q4