Genotoxic evaluation of antiepileptic drugs by Drosophila somatic mutation and recombination test.
The study examines the potential genotoxicity of three antiepileptic drugs (phenytoin sodium, pregabalin, gabapentin) using the wing somatic mutation and recombination test (SMART) in Drosophila melanogaster. Trans-heterozygous (two genetic markers mwh and flr) third-instar larvae of D. melanogaster were treated with different concentrations of the test compounds. A positive correlation was observed between total mutations and the number of wings with morphologically detectable mutations. The observed mutations were classified according to size and type of mutation per wing. Phenytoin clearly increased the frequency of total spots at all concentrations above 1.25 microg/ml. Gabapentin also increased the frequency of total spots at concentrations of 40 and 80 microg/ml. This study shows that phenytoin and gabapentin have genotoxic effects according to the SMART test; however, pregabalin displays lower genotoxicity in the SMAR assay when compared with the other two antiepileptics. The results also show that all AED concentrations lower the survival rate of the flies.
Yüksel
Muammer
M
Department of Neurosurgery, 100 Yıl Hospital, 33 Cadde, Yüzüncüyıl, 06530 Ankara, Turkey.
Sarıkaya
Rabia
R
Bostanci
Neslihan
N
D000014:Abnormalities, Drug-Induced / Q000473:pathology; D000588:Amines / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry / Q000633:toxicity*; D003509:Cyclohexanecarboxylic Acids / Q000737:chemistry / Q000633:toxicity; D004331:Drosophila melanogaster / Q000187:drug effects / Q000235:genetics; D005260:Female; D000077206:Gabapentin; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens; D010672:Phenytoin / Q000737:chemistry / Q000633:toxicity; D000069583:Pregabalin; D011995:Recombination, Genetic / Q000187:drug effects*; D013534:Survival; D014921:Wings, Animal / Q000473:pathology; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000737:chemistry / Q000633:toxicity
D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D009153:Mutagens; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D010672:Phenytoin; D000077206:Gabapentin