In vitro genotoxicity of two widely used benzodiazepines: alprazolam and lorazepam

Abstract

Alprazolam (AZ) and Lorazepam (LZ) belong to benzodiazepines, a multi-membered group of biologically active substances. Even though they are widely used as drugs for the relief of anxiety, sedation and in the treatment of epilepsy, knowledge about their cytogenetic activity is limited.Materials and Methods: In the present study the cytotoxic and cytostatic actions of AZ and LZ have been evaluated in normal human lymphocyte cultures of peripheral blood at final concentrations (0.16-3.84 μM for AZ and 0.62-3.72 μΜ for LZ) equivalent to oral dosage (for AZ 0.25-6 mg/day and for LZ 1-6 mg/day), employing Sister Chromatid Exchanges (SCEs), one of the most sensitive methods reflecting instability of DNA or a deficiency in DNA repair mechanisms, and Proliferation Rate Index (PRI), a valuable indicator of cytostatic activity.Results: After 72h incubation in the cultures, both AZ and LZ caused a dose-dependent, statistically significant increase of SCE frequency (p < 0.001) followed by a statistically significant decrease of PRI (p < 0.001) of lymphocytes.Conclusions: Our results suggest that AZ and LZ at oral doses exhibit statistically significant genotoxicity in normal human lymphocyte cultures

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