Vedat Şekeroğlu

Effects of Viscum album L. extract and quercetin on methotrexate-induced cyto-genotoxicity in mouse bone-marrow cells

Viscum album, a semi-parasitic plant, has been used both in traditional and supplementary medicine in the treatment of many diseases. Quercetin (QE), one of the major flavonoids in some fruits and vegetables, has anti-oxidative and anti-carcinogenic activities. Methotrexate (MTX), an anti-folate anti-metabolite, is a widely used anti-neoplastic drug with significant clastogenic effects. The aim of this study was to investigate the anti-cytogenotoxic effects of pre-treatment with V. album extract (VAE) and QE on MTX-induced chromosomal aberrations (CAs) in mouse bone-marrow cells. Pre-treatment of mice by gavage with VAE (250mg/kgbw/day for 10 days) and QE (50mg/kgbw/day for 10 days) caused a significant decrease in CAs and in the number of aberrant cells with CAs induced by intramuscular treatment of the mice with MTX (10mg/kgbw/day for 3 days), when compared with the group treated with MTX alone. These compounds also significantly increased the mitotic index (MI) in bone-marrow cells that had been suppressed by MTX. In conclusion, from the findings we suggest that VAE and QE may play a role in reducing cyto-genotoxicity induced by anti-neoplastic drugs during cancer chemotherapy.

Effects of commercial formulations of deltamethrin and/or thiacloprid on thyroid hormone levels in rat serum.

Deltamethrin (DEL) and thiacloprid (THIA) are the two commonly used synthetic insecticides applied either separately or as a mixture. The aim of this study was to assess thyroid stimulating hormone (TSH) and the serum levels of thyroid hormones exposure to these compounds in rats. The animals were orally gavaged with a single dose of DEL (15 mg/kg), THIA (112.5 mg/kg) or DEL + THIA (15 + 112.5 mg/kg) for 24 h (acute treatments) or DEL (3 mg/kg per day), THIA (22.5 mg/kg per day) or DEL + THIA (3 + 22.5 mg/kg per day) for 30 days (subacute treatments). Although all independent and combined treatments with DEL and THIA changed the levels of TSH, these alterations were not significant. Statistically significant increases in free triiodothyronine (FT3) and free thyroxine (FT4) serum hormone levels were observed in the independent treatment with THIA and the combined treatment with DEL and THIA for 30 days. The results of this study suggest that in vivo exposure to subacute treatments of commercial formulations of THI and mixture of DEL + THIA increased serum FT3 and FT4 levels in rats. Further studies are required to determine the effects of endocrine disruptors and potential health risks of these insecticides in human, especially in children because of the importance of these hormones during growth and development.

Cytogenetic effects of commercial formulations of deltamethrin and/or thiacloprid on Wistar rat bone marrow cells.

Deltamethrin (DEL) and thiacloprid (THIA) are two insecticides that are widely used in agriculture either separately or in combination. Studies on genotoxicity and cytotoxicity of TIA and the mixture of DEL and THIA insecticides have not been reported so far. Therefore, we investigated the cytotoxic and genotoxic effects of commercial formulations DEL and/or THIA in rat bone marrow cells, using mitotic index (MI), micronucleus (MN) and chromosome aberrations (CA) assay. In vivo cytokinesis‐block micronucleus (CBMN) assay using cytochalasin‐B in bone marrow cells was performed for the first time in this study. Rats were orally gavaged with a single dose of DEL (15 mg/kg), THIA (112.5 mg/kg) or DEL + THIA (15 + 112.5 mg/kg) for 24 h (acute treatments), or DEL (3 mg/kg/day), THIA (22.5 mg/kg/day) or DEL + THIA (3 + 22.5 mg/kg/day) for 30 days (subacute treatments). A corn oil vehicle control group and cyclophosphamide (50 mg/kg) positive control group were also included. All DEL and/or THIA treatments significantly decreased MI and binucleated (BN) cell numbers, and significantly increased CA, as compared to the vehicle control group. The results of CBMN assay indicated that the combination of DEL and THIA for both treatment times and the 30‐day treatment with THIA alone caused a significant increase in micronucleus formation in BN cells. The present findings indicated the combined exposure of DEL and THIA showed genotoxic and cytotoxic effects more than those of individual exposure of DEL or THIA in rat bone marrow cells.

Cytotoxic and genotoxic effects of high-frequency electromagnetic fields (GSM 1800 MHz) on immature and mature rats.

We investigated the cytogenotoxic effects of high frequency electromagnetic fields (HF-EMF) for 45 day and the effect of a recovery period of 15 day after exposure to EMF on bone marrow cells of immature and mature rats. The animals in treatment groups were exposed to 1800 MHz EMF at SAR of 0.37 W/kg and 0.49 W/kg for 2h/day for 45 day. Two recovery groups were kept for a recovery period of 15 day without EMF after exposure to HF-EMF. Two control groups for both immature and mature rats were also included. Significant differences were also observed in chromosome aberrations (CA), micronucleus (MN) frequency, mitotic index (MI) and ratio of polychromatic erythrocytes (PCEs) in all treatment groups. The cytogenotoxic damage was more remarkable in immature rats and, the recovery period did not improve this damage in immature rats. Because much higher and irreversible cytogenotoxic damage was observed in immature rats than in mature rats, further studies are needed to understand effects of EMF on DNA damage and DNA repair, and to determine safe limits for environment and human, especially for children.

Genotoxic and cytotoxic effects of doxycycline in cultured human peripheral blood lymphocytes

Doxycycline (DOX) is a broad-spectrum tetracycline antibiotic used in the treatment of many infections. In this study, the genotoxic and cytotoxic effects of DOX in cultured human peripheral blood lymphocytes were investigated by measuring chromosome aberrations (CAs), cytokinesis-block micronucleus (CBMN) assay, mitotic index (MI), and nuclear division index (NDI). Cultures were treated with DOX at three concentrations (2, 4, and 6 µg/mL) for 48 hours. Mitomycin C (MMC) was used as a positive control. All the tested concentrations of DOX for MI and the higher concentrations (4 and 6 µg/mL) for NDI significantly decreased mitotic activity. However, there are no significant differences between negative control and all the tested concentrations of DOX for CA and MN frequencies. In conclusion, our results indicate that DOX has a cytotoxic effect, but not a genotoxic effect, on human peripheral blood lymphocyte cultures. Further detailed studies, especially about the cell-cycle kinetics of DOX, are required to elucidate the decreases in dividing cells and make a possible risk assessment on cells of patients receiving therapy with this drug. Further, if the specific cytostatic and cytotoxic potential of DOX to different types of cancer cells is investigated in detail, it may also have been used as an antitumoral drug.

Evaluation of the genotoxicity and cytotoxicity of fexofenadine in cultured human peripheral blood lymphocytes.

Fexofenadine (FXF) is a new non-sedating antihistamine used in the treatment of seasonal allergic rhinitis and chronic idiopathic urticaria. Studies on FXF genotoxicity and cytotoxicity in cultured human peripheral blood lymphocytes have not been reported so far. Therefore, the present study is the first report investigating the genotoxic and cytotoxic effects of FXF in cultured human peripheral blood lymphocytes in vitro. Cultures were treated with FXF at three concentrations (50, 100 and 150 μg/ml) for 24 and 48 h. Endpoints analyzed included: mitotic index (MI), nuclear division index (NDI), chromosomal aberrations (CA) and micronucleus (MN) assay. Mitomycin C (MMC) was used as a positive control. The results of CA and MN assays showed that FXF was not genotoxic at all the concentrations tested, meanwhile MI and NDI results showed dose-dependent decrease and significant differences were found for at least one concentration. In conclusion, the results of this study suggest that FXF has a cytotoxic effect but not genotoxic effect on human peripheral blood lymphocyte cultures. Further cytogenetic studies, especially about the cell cycle kinetics of FXF are required to elucidate the decreases in dividing cells, and biomonitoring studies should also be conducted with patients receiving therapy with this drug.

Evaluation of the cytogenotoxic damage in immature and mature rats exposed to 900 MHz radiofrequency electromagnetic fields

Abstract Purpose: One of the most important issues regarding radiofrequency electromagnetic fields (RF-EMF) is their effect on genetic material. Therefore, we investigated the cytogenotoxic effects of 900 MHz radiofrequency electromagnetic fields (RF-EMF) and the effect of a recovery period after exposure to RF-EMF on bone marrow cells of immature and mature rats. Materials and methods: The immature and mature rats in treatment groups were exposed to RF-EMF for 2 h/day for 45 days. Average electrical field values for immature and mature rats were 28.1 ± 4.8 V/m and 20.0 ± 3.2 V/m, respectively. Whole-body specific absorption rate (SAR) values for immature and mature rats were in the range of 0.38–0.78 W/kg, and 0.31–0.52 W/kg during the 45 days, respectively. Two recovery groups were kept for 15 days after RF-EMF exposure. Results: Significant differences were observed in chromosome aberrations (CA), micronucleus (MN) frequency, mitotic index (MI) and ratio of polychromatic erythrocytes (PCE) in all treatment and recovery groups. The cytogenotoxic damage in immature rats was statistically higher than the mature rats. The recovery period did not reduce the damage to the same extent as the corresponding control groups. Conclusions: The exposure of RF-EMF leads to cytotoxic and genotoxic damage in immature and mature rats. More sensitive studies are required to elucidate the possible carcinogenic risk of EMF exposure in humans, especially children.

Effects of tartrazine on proliferation and genetic damage in human lymphocytes

Abstract The color additive, tartrazine (TRZ), is widely used in food products, drugs and cosmetics. Genotoxicity of TRZ and its metabolites has not been investigated in detail in the presence and absence of a metabolic activator (S9 mix) in human. Therefore, the aim of this study is to investigate the cytotoxic and genotoxic effects of TRZ and its metabolites on cultured human lymphocytes by using chromosome aberration (CA) and micronucleus (MN) tests. Cultures were treated with 625, 1250 and 2500 μg/ml of TRZ in the presence and absence of S9 mix. TRZ showed cytotoxic activity at the highest concentration due to significant decrease in mitotic index (MI) in the absence of S9 mix when compared with solvent control. TRZ and metabolites significantly increased the CAs and aberrant cells in the presence and absence of S9 mix at the higher concentrations. Increased MN values in cultures with and without S9 mix were found to significantly at the highest concentration when tested. Our results indicated that while both TRZ and its metabolites have genotoxic potential on human lymphocyte cultures with and without S9 mix, TRZ can induce cytotoxicity at the highest concentration in culture without S9 mix under the experimental conditions.

Argan oil reduces oxidative stress, genetic damage and emperipolesis in rats treated with acrylamide

Acrylamide (AA), a well-known toxicant, is present in high-temperature-processed foods in heated foods. Argan oil (AO), a natural vegetable oil, is receiving increasing attention due to its powerful biological properties. However, limited information is available about its effects in lymphoid organs and bone marrow. The aim of this study is to investigate the effects of AO on hematological parameters, 8-hydroxydeoxyguanosine (8-OHdG), thiobarbituric acid reactive substances (TBARs), protein carbonyl (PCO), glutathione (GSH), myeloperoxidase (MPO) levels, the formation of micronucleus (MN) and megakaryocytic emperipolesis (ME) against AA-induced toxicity in rats. The animals were treated with AA (50mg/kg/day), AO (6ml/kg/day per day) and AA+AO (50mg+6ml/kg/day) for 30days. Treatment of rats with AA significantly decreased the hematological parameters, GSH and MPO activity and PCEs ratio while it increased TBARs, PCOs and 8-OHdG levels and formation of MN and ME. No significant differences were observed in the animals received the AO alone. Co-treatment with AA+AO ameliorated almost all of the alterations caused by AA and exhibited protective effect in rats. Based on the obtained results, we suggest that integration of AO in diet or using its supplements may be a good strategy for improving tissue injury in many diseases.

Acrolein-induced oxidative stress and genotoxicity in rats: protective effects of whey protein and conjugated linoleic acid

Abstract Acrolein (AC), a highly reactive hazardous pollutant, poses serious threats to human health. Whey protein (WP) and conjugated linoleic acid (CLA) have beneficial health implications. We investigated the protective effects of WP and CLA against AC-induced toxicity in rats. The animals were orally gavaged with CLA (200 mg/kg/day), WP (200 mg/kg/day), AC (5 mg/kg/day), CLA + AC (200 + 5 mg/kg/day), and WP + AC (200 + 5 mg/kg/day) six days per week for 30 days. The oral administration of AC significantly induced oxidative stress by increasing thiobarbituric acid reactive substances (TBARS) and protein carbonyls (PCOs) levels and decreasing glutathione (GSH) level in the spleen, thymus, and polymorphonuclear leukocytes (PMNs). It also increased the frequencies of micronucleus (MN) and megakaryocytic emperipolesis (ME) and decreased the ratio of polychromatic erythrocytes (PCEs) in bone marrow. Slight alterations in urinary 8-hydroxydeoxyguanosine (8-OHdG) levels were not significant. Co-treatment with CLA + AC or WP + AC ameliorated the values of oxidative stress, MN, PCE, and ME. These data suggest that CLA and WP can improve the antioxidant defenses and preclude the formation of genetic damage and ME.