In vitro potential cytogenetic and oxidative stress effects of roxithromycin.

Macrolide antibiotic roxithromycin was evaluated in terms of its genotoxic, cytotoxic and oxidative stress effects. For this purpose; 25, 50, 100 and 200 µg/mL concentrations of roxithromycin were dissolved in dimethyl sulfoxide and treated to human peripheral blood lymphocytes for two different treatment periods (24 and 48 h). In chromosome aberration (CA) and micronucleus (MN) tests, roxithromycin did not show genotoxic effect. But it induced sister chromatid exchange (SCE) at the highest concentration (200 µg/mL) for the 24-h treatment period and at all concentrations (except 25 µg/mL) for the 48-h treatment period. Looking at cytotoxic effect of roxithromycin, statistically insignificant decreases on mitotic index and proliferation index were observed. Roxithromycin decreased nuclear division index (NDI) at highest two concentrations (100 and 200 µg/mL) for the 24-h treatment period and at all concentrations (expect 25 µg/mL) for the 48-h treatment period. Total oxidant values, total antioxidant values and oxidative stress index did not change with roxithromycin treatment. Eventually, roxithromycin did not have genotoxic and oxidative stress effects in human-cultured lymphocytes.

In vitro cytogenetic evaluation of the particular combination of flurbiprofen and roxithromycin.

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 H2O2 while in combination with RXM had not the same effect on the plasmid.

Investigation of flurbiprofen genotoxicity and cytotoxicity in rat bone marrow cells.

This study was performed to investigate cytogenetic effects of NSAID flurbiprofen which was used as active ingredient in some analgesic, antipyretic and anti-inflammatory drugs. Genotoxic effect of flurbiprofen was investigated using in vivo chromosome aberration (CA) test and random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) test. Also, oxidative stress potential of flurbiprofen was determined by measuring total oxidant and antioxidant level which occurred with flurbiprofen treatment in rat peripheral blood. For these purposes, rats were treated with three concentrations of flurbiprofen (29.25, 58.50 and 117 mg/kg, body weight) in single dose at two different treatment periods (12 and 24 h). According to the results, flurbiprofen did not affect chromosome aberrations in rat bone marrow cells with CA test. In RAPD-PCR test, polymorphic bands were unaffected. Also, test substance did not change total oxidant and antioxidant status (except for 58.50 and 117 mg/kg, 12 h) and therefore it did not lead to significant increase on oxidative stress (again except 58.50 and 117 mg/kg, 12 h). However, flurbiprofen reduced to mitotic indexes and these reductions were dose-dependent for 12 h treatment. In summary, flurbiprofen did not show significant genotoxic effect. But it caused cytotoxicity in rat bone marrow cells.

Response of the antioxidant enzymes of rats following oral administration of metal-oxide nanoparticles (Al2O3, CuO, TiO2).

Metal-oxide nanoparticles (NPs), as a new emerging technological compound, promise a wide range of usage areas and consequently have the potential to cause environmental toxicology. In the present work, aluminum (Al2O3), copper (CuO), and titanium (TiO2) nanoparticles (NPs) were administered via oral gavage to mature female rats (Rattus norvegicus var. albinos) for 14 days with a dose series of 0 (control), 0.5, 5, and 50 (mg/kg b.w./day). Enzyme activities of the antioxidant system such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST), and glutathione reductase (GR) in the liver were measured. Transmission electron microscope (TEM) images of the liver were taken to demonstrate NP accumulation and distribution in liver tissue. Data showed that all NPs caused some significant (P > 0.05) alterations in the activities of antioxidant enzymes. CAT activity increased after CuO and TiO2 administrations, while SOD activity decreased after Al2O3 administration. The activities of enzymes associated with glutathione (GR, GPx, GST) metabolisms were also significantly altered by NPs. GPx activity increased in rats received Al2O3, CuO NPs, while GR activity increased only by Al2O3. However, there were increases (TiO2) and decreases (CuO) in GST activity in the liver of rats. TEM images of the liver demonstrated that all NPs accumulated in the liver, even at the lowest dose. This study indicated that the antioxidant enzymes in the liver of rats were affected by all NPs, suggesting the antioxidant system of rats suffered after NP administration.