Mehmet Buyukleyla

The effects of thymol on sister chromatid exchange, chromosome aberration and micronucleus in human lymphocytes

The genotoxic effects of thymol were investigated in human peripheral lymphocytes treated with 25, 50, 75, and 100 microg/ml concentrations of thymol for 24 and 48h treatment periods by using sister chromatid exchange (SCE), chromosome aberration (CA), and micronucleus (MN) tests. Nuclear division index (NDI), replication index (RI), and mitotic index (MI) were also calculated in order to determine the cytotoxicity of thymol. Thymol significantly increased the SCE, especially at the lower concentrations. Thymol also increased the SCE at the highest concentrations without statistical significance. Thymol induced both the structural CA and frequency of MN at all concentrations. Thymol dose-dependently decreased the NDI for two treatment periods. Thymol decreased the RI for the 24h treatment time without any statistical significance. However, thymol decreased the RI for the 48h treatment time in a dose-dependent manner. Thymol also decreased the MI at the higher concentration without dose-dependent effect.

Sex-related effects of imidacloprid modulated by piperonyl butoxide and menadione in rats. Part II: genotoxic and cytotoxic potential

Abstract Despite its intended use, imidacloprid causes genotoxic and cytotoxic effects in mammals, especially in the presence of metabolic activation systems. The aim of this study was to determine to which extent these effects are sex related and how its metabolism modulators piperonyl butoxide and menadione affect its toxicity. Male and female Sprague-Dawley rats were injected with the intraperitoneal LD50 dose of imidacloprid alone (170 mg/kg) or pretreated with piperonyl butoxide (100 mg/kg) and menadione (25 mg/kg) for 12 and 24 h. Structural chromosome aberrations, abnormal cells and mitotic index were determined microscopically in bone marrow cells. Male rats showed susceptibility to the genotoxic effects of imidacloprid. Piperonyl butoxide was effective in countering this effect only at 24 h, whereas menadione exacerbated imidacloprid-induced genotoxicity. Piperonyl butoxide and menadione pretreatments increased the percentage of structural chromosome aberrations and abnormal cells in females. Imidacloprid decreased the mitotic index, whereas pretreatment with piperonyl butoxide and menadione showed improvement in both sexes. We believe that CYP450-mediated metabolism of imidacloprid is under the hormonal control and therefore that its genotoxicity is sex related. Piperonyl butoxide pretreatment also showed sex-related modulation. The hormonal effects on imidacloprid biotransformation require further investigation.

Prevalence and Molecular Analysis of β-Thalassemia in Adiyaman, Turkey

Thalassemia is one of the most common hereditary disorders in the Mediterranean region. We report here the results of a premarital screening carried out in Adıyaman in the southeastern region of Turkey, a region with a hitherto unknown incidence of β-thalassemia (β-thal). In order to detect β-thal carrier frequency and genotypes of carriers from the city of Adıyaman, Turkey, both high performance liquid chromatography (HPLC) and the red blood cell counts of 1616 people who applied for premarital tests were analyzed. Blood cell counts were measured by a cell counter and the hemoglobin (Hb) fractionation was carried out by HPLC. The frequency of β-thal carriers in the city of Adıyaman was 1.91% and the frequency of abnormal Hbs was 0.07%. We report 28 chromosomes of β-thal traits with 10 different mutations, including the first report of codon 17 (AAG>TAG) in Turkey and one individual who was heterozygous for Hb D-Los Angeles [β121(GH4)Glu→Gln, GAA>CAA]. This study was the first to be performed on the frequency and molecular pathology of β-thal mutations in Adıyaman in the southeastern region of Turkey. We report that the prevalence of the thalassemia trait is similar in all regions of our country, but the prevalence of mutation heterogeneity varies from region to region.

Effects of natamycin on sister chromatid exchanges, chromosome aberrations and micronucleus in human lymphocytes

Natamycin (pimaricin) (E235) is an antifungal that can be used as an antibiotic to treat most fungus infections. It has been globally used in a variety of foods and beverages. In the present study, the effects of natamycin on chromosome aberrations (CAs), sister chromatid exchanges (SCEs), and micronucleus (MN) formation in human lymphocytes cells were investigated. The human lymphocytes were treated with 13, 18, 23, and 28 μg/mL of natamycin for 24 and 48 h. Natamycin induced the SCE frequency at the highest concentration for 48 h only; however, it induced the structural CA and MN frequency at all concentrations when compared to control and at all concentrations, except the lowest concentration (13 μg/mL), when compared to solvent control. Natamycin showed a cytotoxic effect by decreasing the replication index, mitotic index, and nuclear division index (NDI), especially at the highest concentrations for two treatment periods.

The genotoxic and antigenotoxic effects of tannic acid in human lymphocytes.

The genotoxicity of tannic acid (TA, tannin) were investigated using chromosome aberration (CA), sister chromatid exchange (SCE), and micronucleus (MN) test systems in human peripheral lymphocytes. Also, the antigenotoxicity of TA against known mutagen EMS was also examined. The lymphocytes were treated with 1.74 × 10−5, 3.49 × 10−5, and 6.98 × 10−5 µM of TA for 24- and 48-hour treatment periods. For the antigenotoxicity of TA, the lymphocytes were treated with three different concentrations of TA and 2.71 µM of EMS. TA synergically induced the CA alone and with the mixture of EMS. However, TA did not induce the SCE alone, whereas TA and EMS as a mixture also synergically induced SCE. TA alone showed no clear effect on micronucleus formation, and it did not induce the MN when used with EMS as a mixture. In addition, TA showed a synergistic cytotoxic effect by decreasing the mitotic and nuclear division indices. The replication index was decreased at all concentrations for 48 hours of treatment time by TA and EMS as a mixture.

Sex-, tissue-, and exposure duration-dependent effects of imidacloprid modulated by piperonyl butoxide and menadione in rats. Part I: oxidative and neurotoxic potentials

Abstract Earlier research has evidenced the oxidative and neurotoxic potential of imidacloprid, a neonicotinoid insecticide, in different animal species. The primary aim of this study was to determine how metabolic modulators piperonyl butoxide and menadione affect imidacloprid’s adverse action in the liver and kidney of Sprague-Dawley rats of both sexes. The animals were exposed to imidacloprid alone (170 mg kg-1) or in combination with piperonyl butoxide (100 mg kg-1) or menadione (25 mg kg-1) for 12 and 24 h. Their liver and kidney homogenates were analysed spectrophotometrically for glutathione peroxidase, glutathione S-transferase, catalase, total cholinesterase specific activities, total glutathione, total protein content, and lipid peroxidation levels. Imidacloprid displayed its prooxidative and neurotoxic effects predominantly in the kidney of male rats after 24 h of exposure. Our findings suggest that the observed differences in prooxidative and neurotoxic potential of imidacloprid could be related to differences in its metabolism between the sexes. Co-exposure (90-min pre-treatment) with piperonyl butoxide or menadione revealed tissue-specific effect of imidacloprid on total cholinesterase activity. Increased cholinesterase activity in the kidney could be an adaptive response to imidacloprid-induced oxidative stress. In the male rat liver, co-exposure with piperonyl butoxide or menadione exacerbated imidacloprid toxicity. In female rats, imidacloprid+menadione co-exposure caused prooxidative effects, while no such effects were observed with imidacloprid alone or menadione alone. In conclusion, sex-, tissue-, and duration-specific effects of imidacloprid are remarkable points in its toxicity Sažetak Rezultati ranijih istraživanja pokazali su oksidativni i neurotoksični potencijal imidakloprida, neonikotinoidnog insekticida, u različitih životinjskih vrsta. Primarni je cilj ovog istraživanja bio utvrditi kako modulatori metabolizma piperonil butoksid i menadion utječu na nepovoljne učinke imidakloprida na jetra i bubrege muških i ženskih štakora soja Sprague-Dawley. Životinje su 12 h odnosno 24 h bile izložene samo imidaklopridu (170 mg kg-1) ili njegovoj kombinaciji s piperonil butoksidom (100 mg kg-1) odnosno menadionom (25 mg kg-1). U homogenatima jetara i bubrega spektrofotometrijski su utvrđene razine glutation peroksidaze, glutation S-transferaze, katalaze, specifične aktivnosti ukupne kolinesteraze, ukupni glutation, ukupni proteini te razine lipidne peroksidacije. Imidakloprid se pokazao prooksidativnim i neurotoksičnim uglavnom u bubrezima muških štakora nakon 24-satne izloženosti. Naši rezultati upućuju na to da su razlike u prooksidativnom i neurotoksičnom djelovanju imidakloprida povezane sa spolnim razlikama. Predtretmanom piperonil butoksidom odnosno menadionom (90 min prije davanja imidakloprida) otkriveno je da imidakloprid djeluje na ukupnu aktivnost kolinesteraze specifično za pojedina tkiva. Povišena aktivnost kolinesteraza u bubrezima mogla bi odražavati prilagodbu na oksidativni stres uzrokovan imidaklopridom. Piperonil butoksid odnosno menadion u jetrima muških štakora samo su pogoršali toksičnost imidakloprida. U ženki je djelovanje imidakloprida s menadionom bilo prooksidativno; takvo se djelovanje nije vidjelo nakon primjene samo imidakloprida odnosno samo menadiona. Vjerujemo da je promjenjivo djelovanje imidakloprida s obzirom na spol, tkivo i trajanje izloženosti važno za daljnja istraživanja njegove toksičnosti

In vitro evaluation of the protective effects of 4-thujanol against mitomycin-C and cyclophosphamide-induced genotoxic damage in human peripheral lymphocytes

4-Thujanol (sabinene hydrate), a bicyclic monoterpene alcohol, is found in the essential oils of many aromatic and medicinal plants and is widely used as a fragrance and flavouring agent in many different products. The aim of this study was to evaluate the protective effects of 4-thujanol against the genotoxic effects induced by mitomycin C (MMC) and cyclophosphamide (CP) in human lymphocytes, using the chromosome aberrations, sister chromatid exchanges, and micronucleus tests, in the absence and in the presence of S9 mix, respectively. The cells were treated with 0.25 µg/mL MMC and 28 µg/mL CP as alone and cotreated with 13 + 0.25, 26 + 0.25, and 52 + 0.25 µg/mL 4-thujanol + MMC and with 13 + 28, 26 + 28, and 52 + 28 µg/mL 4-thujanol + CP as a mixture. The present study showed that 4-thujanol was unable to reduce the genetic damage induced by MMC, in the absence of S9 mix. On the other hand, probably the metabolites of 4-thujanol act as an antagonist and markedly antagonize CP-induced genotoxicity, in the presence of S9 mix. In general, 4-thujanol + MMC and 4-thujanol + CP decreased the mitotic index, proliferation index and nuclear division index to the same extent or more than those of individual exposure of MMC or CP. In conclusion, 4-thujanol significantly reduced (p < 0.001) the genotoxic damage induced by CP but not MMC when compared with the respective positive control alone. We can suggest that 4-thujanol may improve the chemopreventive effects and may also reduce the harmful side effects of CP, which is widely used in chemotherapy against cancer, without reducing its antiproliferative activities.