Background and Objective: Amiodarone is an effective antiarrhythmic drug used for cardiac arrhythmias. Due to the presence of iodine in its structure, it tends to accumulate in lipophilic tissues, including the lungs, leading to lung injury and other major adverse effects. The present study aimed to determine the protective effects of vitamin E and the aqueous extract of Thymus vulgaris (T. vulgaris) leaves against amiodarone-induced cytotoxicity in non-cancerous human lung fibroblast (HLF) and human lung cancer (A549) cell lines.
Methods: This descriptive-analytical study was conducted on HLF and A549 cell lines obtained from the Pasteur Institute of Iran in the cell culture laboratory at the Faculty of Pharmacy, Mazandaran University of Medical Sciences. The grouping for non-cancerous HLF and A549 cell lines included a negative control group, a positive control group (amiodarone at its inhibitory concentration [IC₅₀]), treatment groups receiving T. vulgaris and vitamin E at concentrations of 10, 20, and 50 μM, and single-treatment groups receiving T. vulgaris and vitamin E at 50 μM. All experiments were performed in triplicate with an initial cell density of 10⁴ cells per well. To evaluate amiodarone-induced cytotoxicity (5.6 μM), methylthiazolyldiphenyl-tetrazolium bromide (MTT) (48 h), reactive oxygen species (ROS) (6 h), and lipid peroxidation (LPO) (48 h) assays were performed.
Results: The addition of amiodarone to both A549 and non-cancerous HLF cells culminated in a significant decrease in cell viability percentage in the MTT assay (at a concentration of 50 µM T. vulgaris and vitamin E in the normal cell line, and
20 µM T. vulgaris and vitamin E in the A549 cell line). Moreover, it led to a significant increase in ROS (at concentrations of 20 and 50 µM T. vulgaris and vitamin E in the normal cell line, and 20 µM T. vulgaris and vitamin E in the A549 cell line), as well as malondialdehyde (MDA) levels in the LPO assay (at concentrations of 20 and 50 µM T. vulgaris and vitamin E in the normal cell line, and 20 µM T. vulgaris and vitamin E in the A549 cell line) (P<0.05). Furthermore, adding a combination of vitamin E and extract of T. vulgaris leaves in amiodarone-intoxicated non-cancerous HLF cells led to a significant increase in cell viability against IC₅₀ toxicity, alongside a significant reduction in ROS and MDA levels (P<0.05).
Conclusion: The addition of amiodarone to both A549 and non-cancerous HLF cell lines induces cytotoxicity in these cell lines. Concomitant treatment with vitamin E and extract of T. vulgaris leaves in amiodarone-treated cells culminates in a reduction in oxidative damage and an increase in cell viability in non-cancerous HLF cells.