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Evaluating In Vitro DNA Damage Using Comet Assay
Published on: October 11, 2017
The genotoxic and oxidative damage potential of olanzapine in vitro
1Biology Department, Science Faculty, Atatürk University, Erzurum, Turkey.
Abstract:
Olanzapine (OLZ) is an atypical antipsychotic drug and is commonly used for the treatment of schizophrenia and bipolar disorder (BD). However, recent reports indicated that this drug could exhibit cytotoxic effects on nervous and immune systems. To our knowledge, there is scarce data considering the genotoxic or oxidative damage potentials of OLZ on human lymphocyte culture system. Therefore, in this study, the genotoxic potential of OLZ (0 to 160 µM) have been evaluated in human whole blood cultures (WBCs) related to oxidative status. Sister-chromatid exchange (SCE) test was applied to estimate the DNA damage, and biochemical parameters (total antioxidant capacity [TAC] and total oxidative stress [TOS]) were examined to determine oxidative stress. Our results indicated that the tested antipsychotic drug did not induce SCEs in lymphocytes of treated cultures. However, the application of the highest OLZ concentration caused oxidative stress. It is concluded that the OLZ can be used safely, but it is necessary to consider the tissue damages that are likely to appear depending on the oxidative stress.
Insights
Olanzapine (OLZ) did not cause DNA damage in human lymphocytes. However, high doses of this antipsychotic drug induced oxidative stress, suggesting potential tissue damage.
Area of Science:
- Pharmacology
- Toxicology
- Genetics
Background:
- Olanzapine (OLZ) is an atypical antipsychotic used for schizophrenia and bipolar disorder.
- Concerns exist regarding OLZ's potential cytotoxic effects on nervous and immune systems.
- Limited data exists on OLZ's genotoxic and oxidative damage potential in human lymphocytes.
Purpose of the Study:
- To evaluate the genotoxic potential of OLZ in human whole blood cultures (WBCs).
- To assess the impact of OLZ on oxidative status, including total antioxidant capacity (TAC) and total oxidative stress (TOS).
Main Methods:
- Human whole blood cultures were treated with varying concentrations of OLZ (0 to 160 µM).
- Genotoxicity was assessed using the sister-chromatid exchange (SCE) test.
- Oxidative stress markers (TAC and TOS) were measured biochemically.
Main Results:
- Olanzapine did not induce sister-chromatid exchanges (SCEs), indicating no genotoxic effect on lymphocytes.
- The highest concentration of OLZ applied resulted in significant oxidative stress.
- A dose-dependent increase in oxidative stress markers was observed with OLZ treatment.
Conclusions:
- Olanzapine demonstrates a lack of genotoxicity in human lymphocyte cultures.
- High concentrations of OLZ can induce oxidative stress, potentially leading to tissue damage.
- While generally safe, clinical use of OLZ requires consideration of its oxidative stress-inducing properties.
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