Cytotoxicity, genotoxicity, and mutagenicity of the active pharmaceutical ingredient nevirapine and a nevirapine-based drug on the plant species Allium cepa

Abstract

The toxicity of the active pharmaceutical ingredient and nevirapine-based drug at analytical concentrations was evaluated under laboratory conditions, using Allium cepa seeds as a model. The germination index of the negative control was 86.8 ± 2.1. The concentrations of 6.42 and 9.54 mg/L of the active pharmaceutical ingredient and 11.20 mg/L of the nevirapine-based drug showed a statistically higher germination index than the negative control. We found that the root growth of the negative control was 1.7 ± 0.6 mm and that the root growth was statistically lower than the negative control at concentrations of 9.54 and 17.73 mg/L of active pharmaceutical ingredient and 5.48, 11.20, and 17.68 mg/L of the drug. The mitotic index of negative control and methyl methanesulfonate were 7.4 ± 2.7 and 12.8 ± 4.5, respectively. At a concentration of 17.68 mg/L of the nevirapine-based drug, the mitotic index of 12.7 ± 2.7 was statistically higher than the negative control and like the methyl methanesulfonate, which indicated that nevirapine was cytotoxic at this concentration. At all concentrations tested the chromosome abnormality indices were statistically higher than negative control, suggesting that nevirapine was genotoxic. The mutagenicity index of the negative control was 0.2 ± 0.3. At concentrations of 6.42, 9.54, and 17.73 mg/L of the active pharmaceutical ingredient and 17.68 mg/L of the nevirapine-based drug, the mutagenicity index was statistically higher than the negative control, indicating that nevirapine was mutagenic for A. cespa at these concentrations. The chromosomal adhesion was the most frequent chromosomal aberration in the groups exposed to nevirapine, suggesting that it has an aneugenic effect on the A. cepa species.