Sertraline (SRT) is an antidepressant agent used as a neuronal selective serotonin-reuptake inhibitor (SSRI). SRT blocks serotonin reuptake and increases serotonin stimulation of somatodendritic serotonin 1A receptor (5-HT1AR) and terminal autoreceptors in the brain. In the present study, the genotoxic potential of SRT was evaluated using cytokinesis-block micronucleus (CBMN) cytome assay in peripheral blood lymphocytes of healthy human subjects. DNA cleavage-protective effects of SRT were analyzed on plasmid pBR322. In addition, biochemical parameters of total oxidant status (TOS) and total antioxidant status (TAS) in blood plasma were measured to quantitate oxidative stress. Human peripheral blood lymphocytes were exposed to four different concentrations (1.25, 2.5, 3.75 and 5 μg/mL) of SRT for 24- or 48-h treatment periods. In this study, SRT was not found to induce MN formation either in 24- or 48-h treatment periods. In contrast, SRT concentration-dependently decreased the percentage of MN and MNBN (r=–0.979, p<0.01; r=–0.930, p<0.05, respectively) when it was present for the last 48 hr (48-h treatment) of the culture period. SRT neither demonstrated a cleavage activity on plasmid DNA nor conferred DNA protection against H2O2. The application of various concentrations of SRT significantly increased the TOS and oxidative stress index (OSI) in human peripheral blood lymphocytes for both the 24- and 48-h treatment periods. Morover, the increase in TOS was potent as the positive control MMC at both treatment times. However, SRT did not alter the TAS levels in either 24- or 48-h treatment periods when compared to control. In addition, exposing cells to SRT caused significant decreases in the nuclear division index at 1.25, 2.50 and 3.75 μg/mL in the 24-h and at the highest concentration (5 μg/mL) in the 48-h treatment periods. Our results suggest that SRT may have cytotoxic effect via oxidative stress on cultured human peripheral blood lymphocytes.
4-Methylimidazole (4-MEI), a heterocyclic organic chemical compound, is widely found in many foods and consumed by people worldwide. In this research, we aimed to investigate the cytotoxic and genotoxic effects of 4-MEI on human lymphocytes. For this purpose, human peripheral blood lymphocytes were treated with four concentrations of 4-MEI (300, 450, 600 and 750 μg/ml) for 24 h and 48 h periods and in vitro sister chromatid exchange (SCE), chromosome aberration (CA) and micronucleus (MN) tests were used. 4-MEI induced SCE in human peripheral lymphocytes at three highest concentrations (450, 600 and 750 μg/ml) in 48 h treatment period. CA and MN were induced in human peripheral lymphocytes at two highest concentrations of 4-MEI (600 and 750 μg/ml) in 24 h and 48 h treatment periods. The highest concentration of 4-MEI (750 μg/ml) induced MN formation more than the positive control MMC in 24 h treatment period. In addition, 4-MEI led to a decrease in MI at the highest concentration (750 μg/ml) in 24 h treatment period and at all concentrations in 48 h treatment period. 4-MEI reduced PI at all concentrations in 24 h treatment period and at all concentrations (expect the lowest) for 48 h treatment period. 4-MEI reduced nuclear division index (NDI) at 24 and 48 h treatment periods, even at the highest two concentrations, decreased more than the positive control MMC. Our results showed that 4-MEI pose a genotoxic and cytotoxic effects for human peripheral lymphocytes.
Flurbiprofen (FLB) (anti-inflammatory and analgesic drug) and roxithromycin (RXM) (antibiotic) were widely used in world wide. This study deals with investigation of genotoxicity, cytotoxicity, and oxidative stress effects of a particular combination of these drugs in human cultured lymphocytes. Also, DNA damaging-protective effects of combination of these drugs were analyzed on plasmid DNA. Human lymphocytes were treated with different concentrations (FLB + RXM; 10 μg/mL + 25 μg/mL, 15 μg/mL + 50 μg/mL, and 20 μg/mL + 100 μg/mL) of the drugs following by study of their genotoxic and cytotoxic effects by analysis of cytokinesis-block micronucleus test and nuclear division index, respectively. The effect of the combination in aspect of anti-oxidative and DNA damaging activity was evaluated on Pet-22b plasmid. According to our results, the combination of FLB and RXM did not show a notable genotoxic effect on cells. Although each of the substances had been shown as a cytotoxic agent by previous researchers, in this research, the combination of these drugs did not exhibit any adverse effect on cell division. FLB had DNA protection effect against HO while in combination with RXM had not the same effect on the plasmid.
Bu çalışma antitiroid ilaç Propycil®'in çeşitli test bakterileri üzerindeki antibakteriyel aktivitesinin belirlenmesi ve potansiyel mutajenik etkisinin Ames / Salmonella / Mikrozom test sistemi ile saptanması amacıyla yapılmıştır. Antibakteriyel aktivite testleri esnasında test bakterisi olarak Staphylococcus aureus ATCC 6538, Pseudomonas aeruginosa ATCC 9027, Bacillus megaterium DSM 32 ve klinik izolat olan Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae kullanılmıştır. Mutajen etki çalışmalarında ise Ames Testi tercih edilmiş olup, Salmonella typhimurium TA 98 ve TA 100 suşları kullanılmıştır. Elde edilen bulgular neticesinde Propycil®'in test edilen bakterilerinden sadece Klebsiella pneumoniae'ye karşı 13,35 mm ve Pseudomonas aeruginosa ATCC 9027'ye karşı ise 15,46 mm inhibisyon zonu oluşturduğu tespit edilmiştir. Ames testi sonucunda denenen dozların hiç biri TA 98 suşu üzerinde çerçeve kayması mutasyonuna neden olmazken, TA 100 suşu üzerinde denenen en yüksek doz hariç diğer tüm dozlar baz çifti değişimi mutasyonuna sebep olduğu belirlenmiştir.
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