1- a Lebanese University, Faculty of Sciences, Sections I and III, Tripoli - Lebanon; b Lebanese University, Faculty of Public Health, Sections I and IV, Zahleh – Lebanon; c Jinan University, Faculty of Public Health , houssein.al-attrache@ul.edu.lb
2- a Lebanese University, Faculty of Sciences, Sections I and III, Tripoli - Lebanon; b Lebanese University, Faculty of Public Health, Sections I and IV, Zahleh – Lebanon;
3- Lebanese University, Faculty of Sciences, Sections I and III, Tripoli - Lebanon
4- a Lebanese University, Faculty of Sciences, Sections I and III, Tripoli - Lebanon
2- a Lebanese University, Faculty of Sciences, Sections I and III, Tripoli - Lebanon; b Lebanese University, Faculty of Public Health, Sections I and IV, Zahleh – Lebanon;
3- Lebanese University, Faculty of Sciences, Sections I and III, Tripoli - Lebanon
4- a Lebanese University, Faculty of Sciences, Sections I and III, Tripoli - Lebanon
Abstract: (67 Views)
Background: Amiodarone (AMD) is an antiarrhythmic drug that induces idiosyncratic toxicity. Different physicochemical parameters could interact with its toxicity by affecting pharmacokinetics and pharmacodynamics. In the present study, we investigated the effects of temperature, pH, electrical current, and ultraviolet (UV) on the toxicity of this drug in the wild type BY4741 of Saccharomyces cerevisiae.
Materials and Methods: The percentage of growth and half inhibitory concentration (IC50) of AMD under different conditions were calculated using GraphPad Prism after measuring yeast growth with a spectrophotometer.
Results: Based on the findings obtained, amiodarone alone decreased yeast growth in a dose‑dependent manner and was accompanied by reduced CO₂ release, suggesting a possible role of fermentation in protecting cells from the drug’s toxicity. Acidic pH increased the inhibitory effect of AMD on growth by lowering the IC50, while basic pH decreased this effect by raising the IC50. Toxicity also increased when cells were exposed to a temperature of 50 °C, indicating that yeasts were sensitized through stress induction. However, exposure to a low temperature of -20 °C had no effect. On the other hand, the growth inhibition of BY4741 was slightly reduced when irradiated by UV, indicating a possible effect on cell proliferation. A similar effect was observed in cells exposed to a voltage of 9 V, which increased the IC50. This may be due to the influence of current on AMD’s membrane transporters.
Conclusion: Overall, pH, temperature, UV, and an electric current can modify the toxicity induced by AMD in yeast, indicating the possibility of the influence of physicochemical parameters on the toxicity of this idiosyncratic drug.
Materials and Methods: The percentage of growth and half inhibitory concentration (IC50) of AMD under different conditions were calculated using GraphPad Prism after measuring yeast growth with a spectrophotometer.
Results: Based on the findings obtained, amiodarone alone decreased yeast growth in a dose‑dependent manner and was accompanied by reduced CO₂ release, suggesting a possible role of fermentation in protecting cells from the drug’s toxicity. Acidic pH increased the inhibitory effect of AMD on growth by lowering the IC50, while basic pH decreased this effect by raising the IC50. Toxicity also increased when cells were exposed to a temperature of 50 °C, indicating that yeasts were sensitized through stress induction. However, exposure to a low temperature of -20 °C had no effect. On the other hand, the growth inhibition of BY4741 was slightly reduced when irradiated by UV, indicating a possible effect on cell proliferation. A similar effect was observed in cells exposed to a voltage of 9 V, which increased the IC50. This may be due to the influence of current on AMD’s membrane transporters.
Conclusion: Overall, pH, temperature, UV, and an electric current can modify the toxicity induced by AMD in yeast, indicating the possibility of the influence of physicochemical parameters on the toxicity of this idiosyncratic drug.
Keywords: Amiodarone, Chemical and physical Factors, Drug Toxicity, Growth, Saccharomyces cerevisiae
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