Hasan Türkez

Propolis prevents aluminium-induced genetic and hepatic damages in rat liver.

Aluminium is present in several manufactured foods and medicines and is also used in water purification. Therefore, the present experiment was undertaken to determine the effectiveness of propolis in modulating the aluminium chloride (AlCl(3)) induced genotoxicity and hepatotoxicity in liver of rats. Animals were assigned to 1 of 4 groups: control; 34 mg AlCl(3)/kg bw; 50mg propolis/kg bw; AlCl(3) (34 mg/kg bw) plus propolis (50mg/kg bw), respectively. Rats were orally administered their respective doses daily for 30 days. At the end of the experiment, rats were anesthetized and hepatocytes (HEP) were isolated for counting the number of micronucleated hepatocytes (MNHEPs). In addition, the levels of serum enzymes and histological alterations in liver were investigated. AlCl(3) caused a significant increase in MNHEPs, alkaline phosphatase, transaminases (AST and ALT) and lactate dehydrogenase (LDH). Furthermore, severe pathological damages such as: sinusoidal dilatation, congestion of central vein, lipid accumulation and lymphocyte infiltration were established in liver. On the contrary, treatment with propolis alone did not cause any adverse effect on above parameters. Moreover, simultaneous treatments with propolis significantly modulated the toxic effects of AlCl(3). It can be concluded that propolis has beneficial influences and could be able to antagonize AlCl(3) toxicity.

Effects of Some Boron Compounds on Peripheral Human Blood

Peripheral blood cultures were exposed to various doses (5 to 500 mg/L) of boron compounds. Sister-chromatid exchange, micronucleus and chromosomal aberration tests were applied to estimate the DNA damage, and biochemical parameters (superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glucose-6-phosphate dehydrogenase, total glutathione, malondialdehyde and total antioxidant capacity) were examined to determine oxidative stress. According to our findings, various boron compounds at low doses were useful in supporting antioxidant enzyme activities in human blood cultures. It was found that the boron compounds do not have genotoxic effects even in the highest concentrations, though in increasing doses they constitute oxidative stress. It is concluded that the tested boron compounds can be used safely, but it is necessary to consider the tissue damages which are likely to appear depending on the oxidative stress.

The effects of some boron compounds against heavy metal toxicity in human blood.

Heavy metals can accumulate in the environment and cause serious damages to ecosystems and human health. Boron is considered to be essential micronutrient with its well established biological functions and the antioxidant effects of boric acid (BA) are controversial. However, the potential of important boron compounds in cellular activities remains unexplored. Therefore, we aimed to assess the efficacies of some boron compounds (BA, borax, colemanite and ulexite) on the genotoxicity induced by heavy metals (arsenic trioxide, colloidal bismuth subcitrate, cadmium chloride, mercury chloride and lead chloride) in human blood cultures. For this aim, sister chromatid exchange (SCE) and micronuclei (MN) assays were performed to establish DNA damages in lymphocytes. Besides, oxidative stress was monitored by estimating the changes of main antioxidant enzyme activities and the levels of total glutathione (TGSH) in erythrocytes. The present study showed that heavy metal treatments increased the frequencies of SCE and MN and the plasma malondialdehyde (MDA) level; decreased the antioxidant enzyme activities and the level of TGSH compared to controls. Whereas, the tested boron compounds (5-20 ppm) significantly reduced the genotoxic effects induced by low doses of heavy metals. Our results revealed that the protective roles of boron compounds occurred with the effectiveness on their anti-oxidant capacity. In conclusion, these compounds could be useful in the development of functional food and raw materials of medicine.

An in vitro blood culture for evaluating the genotoxicity of titanium dioxide: the responses of antioxidant enzymes:

Titanium dioxide (TiO 2) is extensively used in many industrial areas, including cosmetics, pharmaceutical, paint and paper production. Although the uses of TiO 2 have become so widespread, there is limited information concerning its toxicity on humans. However, the genotoxicity of TiO2 remains to be controversial. The possible genotoxic effects of TiO2 have been evaluated in human whole blood cultures (WBCs) related to oxidative status. The blood was processed to examine the following oxidative stress markers: glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase. In addition, the frequencies of sister-chromatid exchanges (SCEs) and micronuclei (MN) were scored as genetic endpoints. Different concentrations of TiO2 (1, 2, 3, 5, 7.5 and 10 μM) were tested. From the results, it appeared that TiO2 was able to induce genotoxic effects, as observed by the increases found in SCE and MN frequencies in TiO2-treated cultures. Present results also show that treatments with TiO2 promoted oxidative stress in human WBC with an increase in concentrations. In conclusion, our data indicate that TiO2 can enhance oxidative stress-mediated DNA damage in vitro. Toxicology and Industrial Health 2007; 23: 19—23.

Antimutagenic effects of lichen Pseudovernia furfuracea (L.) Zoph. extracts against the mutagenicity of aflatoxin B1 in vitro

The aim of this study was to investigate the effects of methanol, acetone, n-hexane and ether extracts obtained from Pseudovernia furfuracea on genotoxicity and total antioxidant capacity (TAC) in cultured human blood cells intoxicated with aflatoxin B 1 (AFB1). Sister chromatid exchange (SCE) and micronucleus (MN) tests were used for genotoxic influences estimation. In both the test systems, it was observed that P. furfuracea extracts suppressed the mutagenic effects of AFB1 due to the type of extracts added to the cultures. Furthermore, a significant reduction in plasma TAC was observed after AFB 1 treatment. Interestingly, the methanol and acetone extracts of the lichen recovered AFB1-induced TAC inhibition. The order of extracts of anti-genotoxicity efficacy against AFB1 was methanol, acetone, ether and n-hexane, respectively. In conclusion, P. furfuracea has been shown to modulate the adverse effects of AFB1 in human blood cells for the first time.

The role of ascorbic acid on titanium dioxide-induced genetic damage assessed by the comet assay and cytogenetic tests

Titanium dioxide (TiO(2)) is used in several commercial products such as cosmetics, sunscreen, toothpaste and pharmaceuticals. However, some recent investigations have revealed that titanium particles generate potential harmful effects on the environment and humans. Because of its strong antioxidant activity, ascorbic acid (AA) is admitted to act as an anti-mutagenic agent. The present study was undertaken to investigate the protective effect of AA against TiO(2)-induced genotoxicity. Sister chromatid exchange (SCE), micronucleus (MN) and the comet assays were used to assess TiO(2)-induced genotoxicity and to establish the protective effects of AA. There were significant increases (P<0.05) in both SCE and MN frequencies of cultures treated with TiO(2) as compared to controls. However, co-application of AA (4.87 and 9.73 μM) and TiO(2) resulted in decreases of SCE and MN rates as compared to the group treated with titanium alone. Besides, significant reductions of primary DNA damage (comet assay) were determined when the AA was added to the cell culture medium simultaneously with TiO(2). In conclusion, the preventive role of AA in alleviating TiO(2)-induced DNA damage was indicated for the first time in the present study.

Toxicologic evaluation of imazalil with particular reference to genotoxic and teratogenic potentials

Imazalil (IMA) is a fungicide that is used extensively in fruit plantations and post-harvest treatments. IMA is suspected to produce craniofacial malformations in vertebrates and scarce data are available about its genotoxicity. Therefore, toxicity tests on embryogenesis of zebrafish (Danio rerio) and genotoxicity biomonitoring assays on human lymphocytes were performed to assess the effects of IMA. For this aim, zebrafish embryos were continually exposed, from 0.5 to 144 h post-fertilization, to a range of concentrations (5, 10, 20, 50 and 100 µM). IMA (0 to 672 µM) were also applied to the whole-blood cultures from two persons. We used chromosomal aberrations (CA) and micronucleus (MN) tests to examine DNA damage by IMA in human peripheral lymphocytes. The fungicide significantly altered zebrafish development even at low concentrations and its effects were dose-dependent. Results of the experiment indicated that IMA concentrations of 10 µM and above negatively affected embryo survival and hatching success. Morphological analysis uncovered a large suite of abnormalities such as less melanin pigmentation, wavy notochord, crooked trunk, tail defect and cardiac edema. The cytogenetic results clearly showed that IMA caused increases of the frequencies of the structural chromosomal aberrations and the rates of MN as compared to controls in a dose-dependent manner. In conclusion, the present findings are of importance in the assessment of the potential risk of fungicides as IMA on aquatic ecosystems and humans.

The protective roles of some lichen species on colloidal bismuth subcitrate genotoxicity.

Medicinal plants are increasingly being projected as suitable alternative source for the treatment of various diseases. However, toxic effects resulting from therapeutic bismuth compounds are still documented in animals and humans. This study described the genetic effects of five common lichen species and compared their activities on the genotoxicity induced by the colloidal bismuth subcitrate. After the application of colloidal bismuth subcitrate and lichen extracts, separate and together, human whole blood cultures were assessed by sister-chromatid exchange (SCE) and micronucleus tests. According to our results, the frequencies of SCE and micronucleus rate in peripheral lymphocytes were significantly increased by colloidal bismuth subcitrate (at dose 5 μg/mL) compared with controls. However, lichen extracts had no genotoxic effect. The order of anti-genotoxicity efficacy against colloidal bismuth subcitrate was Pseudevernia furfuracea, Dermotocarpon intestiniforme, Ramalina capitata, Parmelia pulla, respectively. However, Rhizoplaca melanophthalma did not show any effect against colloidal bismuth subcitrate genotoxicity. Present findings showed that the protective roles of lichens studied were dose related. In conclusion, this is the first study report describing the therapeutic potential of lichens against drug genotoxicity in human blood.

The genotoxic and oxidative damage potential of olanzapine in vitro

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.

The genotoxic, hepatotoxic, nephrotoxic, haematotoxic and histopathological effects in rats after aluminium chronic intoxication

Aluminium (Al) is used in water purification and is also present in several manufactured foods and medicines. Al is known to induce a broad range of physiological, biochemical and behavioural dysfunctions in laboratory animals and humans. This investigation was carried out to investigate the effects of subchronic exposure to Al (as AlCl3) in rats. Sprague-Dawley rats were randomly separated into two groups. Group 1 rats treated with sodium chloride served as the control, group 2 rats were treated with Al (as AlCl3, 5 mg/kg body weight) intraperitonally for 10 weeks. Animals were killed and blood samples were analyzed for blood serum alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) enzyme activities and creatinine, urea (U) and uric acid (UA) levels for evaluating hepatotoxicity and nephrotoxicity. Blood parameters including red blood cells (RBCs), haemoglobin (Hb) concentration, haematocrit (Ht), platelets (PLTs) and white blood cells (WBCs) were compared between control and experimental group to assess haematoxicity. In order to determine the genotoxicity, the number of micronucleated hepatocytes (MNHEPs) was counted in isolated hepatocytes. In addition, histological alterations in liver and kidney samples were investigated. After exposure with Al, the enzymatic activities of ALP, AST, ALT and LDH, and the levels of U and UA significantly increased. RBC, WBC, PLT, Hb and Ht revealed significant decreases in experimental group compared to the control. AlCl3 caused a significant increase in MNHEPs. Furthermore, severe pathological damages were established in both liver and kidney samples. Subchronic exposure to low doses of Al can produce serious dysfunctions in rat blood, liver and kidney, and exposure to this metal can result in greater damages.