Antigenotoxic Effects Research Articles

Antigenotoxic and antimutagenic effects of Myrciaria dubia juice in mice submitted to ethanol 28-day treatment

ABSTRACTMyrciaria dubia is a native plant from the Amazon region which produces red-purplish fruit rich in antioxidant compounds such as ascorbic acid, carotenoids, and phenolic. M. dubia fruit is used to prepare juices considered to possess high nutritional content providing health benefits. The aim of this study was to examine the ability of M. dubia juice to protect DNA against genomic instability induced by sub-acute ethanol consumption attributed to oxidative stress. Mice were treated for 28 days with juice at 25% and 50% diluted in distilled water or with the diluted combination juice plus ethanol (5 g/kg). The genotoxic/antigenotoxic and mutagenic/antimutagenic effects were assessed using comet assay in blood, liver, and kidney and micronucleus (MN) test with bone marrow. In addition, the mutagenicity was also evaluated using Salmonella/microsome assay. Phytochemical compounds were determined using HPLC/PDA/MS/MS. The juice did not induce genotoxic effects in blood, kidney, and liver cells at both doses. In combination with ethanol, the juice reduced the alcohol-mediated DNA damage in all tissues analyzed. Further, the juice did not produce mutagenic effects and decreased mutagenicity induced by ethanol in the bone marrow. The anthocyanins were major compounds detected by HPLC/PDA/MS/MS, which modulated genotoxic and mutagenic effects initiated by ethanol and at least in part appeared responsible for the observed antigenotoxic and antimutagenic effects of M. dubia juice.

Anti-genotoxic potential of Gentiana lutea extracts against the food sweetener saccharin

Sweeteners are now an integral part of the food industry. Despite its long history of use, saccharin has been in the spotlight for many reasons including toxicity, cancerogenicity and other health issues. Because of this, it is necessary to find natural supplements that could reduce the negative effect of this sweetener. The aim of the study was to investigate the potential anti-genotoxic effect of Gentiana lutea plant extracts against saccharin-induced genotoxicity. G. lutea is widely used in traditional medicine and in the food and pharmaceutical industries. The anti-genotoxicity of root and leaf 50% aqueous-ethanolic extracts was tested on normal human fetal fibroblasts (MRC-5) and human hepatocarcinoma cells (HepG2) using the comet assay. G. lutea extracts significantly reduced the genotoxic effect of saccharin at all tested concentrations. The results obtained in this study indicate the strong protective effect of G. lutea against saccharin-induced DNA damage and encourage further studies in order to use this plant as a source of natural food supplements.

Protective effect of Gentiana lutea root and leaf extracts against heterocyclic aromatic amines IQ and PhIP produced in thermally processed meat

During high-temperature cooking of protein rich foods, especially meat and fish, heterocyclic aromatic amines can be formed. These amines are a class of potent mutagens that can cause alterations in the structure of DNA and chromosomes. In recent decades, research has been focused on investigating plants and their phytochemicals as potential antimutagens. The aim of this study was to examine the anti-genotoxic effect of methanolic root and leaf extracts of Gentiana lutea against the food mutagens 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) produced in thermally processed meat. To determine the protective potential of extracts, the alkaline comet assay was applied. The results obtained indicated strong anti-genotoxic effect of both extracts against the tested mutagens. The highest inhibition of IQ-induced genotoxicity was recorded for leaf extract (72%). Regarding PhiP, root extract achieved inhibition of 80% of DNA damage, so was more successful than leaf extract. The data obtained in this study stimulates further research of G. lutea extracts and its constituents as potential dietary supplements in improving human health.

Modulation of hepatic ABC transporters by Eruca vesicaria intake: Potential diet-drug interactions

The aim of this work was to evaluate whether oral administration of Eruca vesicaria, a species of rocket cultivated in Argentina, could modify cyclophosphamide (CP)-induced genotoxicity through modulation of hepatic ABC transporters. Daily oral administration of E. vesicaria fresh leaves juice (1.0, 1.4 and 2.0 g/kg) for 14 days did not alter genotoxicity biomarkers —alkaline comet assay and micronucleus test —in neither male nor female mice. Instead, repeated intake of this cruciferous decreased CP-induced DNA damage dose-dependently and it caused hepatic overexpression of P-glycoprotein (P-gp; 1.4 and 2.0 g/kg) and multidrug resistance protein 2 (MRP2; 2.0 g/kg), but not breast cancer resistance protein (Bcrp). The antigenotoxic effect of E. vesicaria was prevented by 50 mg/kg verapamil (P-gp inhibitor) or 10 mg/kg indomethacin (MRP2 inhibitor). In turn, CP-induced cytotoxicity (10 mM, 24 h) on human hepatoma cells (HepG2/C3A) was significantly reduced by preincubation with E. vesicaria (1.4 mg/ml; 48 h); this effect was absent when CP was coincubated with 35 μM verapamil, 80 μM indomethacin or 10 μM KO-143 (BCRP inhibitor).Altogether, these results allow us to demonstrate that repeated intake of E. vesicaria exhibited antigenotoxicity, at least in part, by induction of hepatic ABC transporters in vivo in mice as well as in vitro in human liver cells. This could account for other diet-drug interactions.

Protective effects of Ginkgo biloba L. against natural toxins, chemical toxicities, and radiation: A comprehensive review.

Nowadays in our developing and industrial world, humans' health or even their life is threatened by exposure to poisons. In this situation, detecting a protective compound could be helpful and interesting. In the present article, we collected and reviewed all studies, which have been conducted so far about the protective effects of Ginkgo biloba L. (GB), one of the most ancient medicinal tree species, against toxicities induced by chemical toxic agents, natural toxins, and also radiation. In overall, investigations showed that GB exerts the antioxidant, antiinflammatory, antiapoptotic, and antigenotoxicity effects in different toxicities. There are also some special mechanisms about its protective effects against some specific toxic agents, such as acetylcholine esterase inhibition in the aluminium neurotoxicity or membrane-bond phosphodiesterase activation in the triethyltin toxicity. Ginkgolide A was the most investigated active ingredient of G. biloba leaf extract as a protective compound against toxicities, which had the similar effects of total extract. A few clinical studies have been conducted in this field, which demonstrated the beneficial effects of GB against toxic agents. However, the promising effects of this valuable herbal extract will practically remain useless without carrying out more clinical studies and proving its effects on human beings.

Genotoxic and antigenotoxic potential of herbal mixture and five medicinal plants used in ethnopharmacology

One of the commonly used herbal preparation in traditional medicine is made of Rubus fruticosus leaves, Vaccinium myrtillus leaves, Potentilla erecta roots, Geum urbanum aerial parts and Phaseolus vulgaris pods, but little is known about potential toxicity and antitoxicity of these medicinal plants and their accumulated biological effect when used as a herbal mixture. In the present study, possible cytotoxic/genotoxic and anticytotoxic/ antigenotoxic effects of the tested extracts were evaluated using the Allium cepa assay and RBCs antihaemolytic test. Determined by the A. cepa genotoxicity assay, the lowest genotoxic effect was expressed by the herbal mixture extract, and the highest one by P. vulgaris and V. myrtillus. In the A. cepa antigenotoxicity assay, the herbal mixture (45 μg/ml) and P. vulgaris (70 μg/ml) had the highest capacity to reverse chromosomal aberrations caused by ROS. All the extracts in lower concentrations (25, 50 and 100 μg/ml) showed strong antihaemolytic activity. The present study concluded that, although all the extracts expressed high protective activity against cell damage caused by oxidative stress, the most beneficial use of these medicinal plants is when used as a mixture prepared according to a precisely defined recipe.

Antigenotoxic and antioxidant potential of medicinal mushrooms (Immune Assist) against DNA damage induced by free radicals-an in vitro study

Immune Assist (IA) is produced from extract of six species of medical mushrooms: Agaricus blazei - Cordyceps sinensis - Grifola frondosa - Ganoderma lucidum - Coriolus versicolor - Lentinula edodes. The genoprotective potential of IA was evaluated for the first time. Significant antigenotoxic effects were detected in human peripheral blood cells against H2O2 induced DNA damage, in the pretreatment and in the posttreatment. The most efficient concentration of IA in pretreatment was 500 μg/mL, while in posttreatment it was the concentration of 250 μg/mL. Kinetics of attenuation of H2O2 induced DNA damage in posttreatment with the optimal concentration of IA showed significant decrease in the number of damaged cells at all time periods (15–60 min), reaching the greatest reduction after 15 and 45 min. Remarkable ·OH scavenging properties and moderate reducing power, together with the modest DPPH scavenging activity, could be responsible for the great attenuation of DNA damage after 15 min of exposure to IA, while reduction of DNA damage after 45 min could be the result in additional stimulation of the cell’s repair machinery. Our results suggest that IA displayed antigenotoxic and antioxidant properties. A broader investigation of its profile in biological systems is needed.

Determination of genotoxic and antigenotoxic effects of wild-grown Reishi mushroom (Ganoderma lucidum) using the hen’s egg test for analysis of micronucleus induction

ABSTRACTThe micronucleus (MN) technique is commonly used for genotoxicity testing. The hen’s egg test (HET) for analysis of MN induction (HET-MN) is an inexpensive, rapid and simple genotoxicity assay that is compatible with animal protection and ethical considerations. Ganoderma lucidum (Curtis) P. Karst is known also as reishi mushroom and mushroom of immortality. It has long been used to treat disorders including fungal infections, influenza, common cold, hepatitis, diabetes, high cholesterol and cancer in many countries including China and Japan. G. lucidum strengthens the immune system and reduces the side effects of chemo- and radiotherapy. We investigated the possible genotoxic and antigenotoxic effects of the aqueous extract of wild-grown G. lucidum from Turkey using the HET-MN test. Three different doses of aqueous extract of G. lucidum, 50 µg/egg vitamin C as an antigenotoxic agent and 50 µg/egg cyclophosphamide as a genotoxic compound were injected separately or together into fertilized chicken eggs at incubation day 8. Embryonic peripheral blood smears were prepared and stained with a modified May-Grünwald-Giemsa method on incubation day 11. The frequencies of MN and nuclear abnormalities in erythrocytes were determined using light microscopy. Although the aqueous extract G. lucidum exhibited no genotoxic effect, it did exhibit an antigenotoxic effect. Our findings suggest that G. lucidum extract is a valuable natural antigenotoxic agent.

Evaluation of genotoxicity and coumarin production in conventional and organic cultivation systems of Mikania glomerata Spreng

Mikania glomerata Sprengel, popularly known as “guaco,” is used in Brazilian folk medicine for several inflammatory and allergic conditions. Besides, the popular use “guaco” is indicated by the Brazilian Ministry of Health as a safe and effective herbal medicine. The biological activity of M. glomerata extracts is due to the presence of the coumarins, a large family of phenolic substances found in plants and is made of fused benzene and α-pyrone rings. Considering that there are few data on the biological effects of the extracts of M. glomerata, mainly in genetic level, this work aims to evaluate, in vitro, the genotoxicity and coumarin production in M. glomerata in conventional and organic growing. The data showed that the organic culture system showed double the concentration of coumarin being significantly more productive than the conventional system. Besides, the results of comet assay suggest that extracts of M. glomerata cultivated in a conventional system was genotoxic, increased DNA damage levels while the organic extracts seem to have antigenotoxic effect possibly due to the concentration of coumarins. Additional biochemical investigations are necessary to elucidate the mechanisms of action of M. glomerata extracts, which were found to have a role in protection against DNA damage.

Nutraceutic Potential of Two Allium Species and Their Distinctive Organosulfur Compounds: A Multi-Assay Evaluation.

This study aimed to evaluate the biological activities of two Allium species (garlic and onion) as well as diallyl disulphide (DADS) and dipropyl disulphide (DPDS) as their representative bioactive compounds in a multi-assay experimental design. The genotoxic, antigenotoxic, and lifespan effects of garlic, onion, DADS, and DPDS were checked in Drosophila melanogaster and their cytotoxic, pro-apoptotic, and DNA-clastogenic activities were analyzed using HL60 tumoral cells. All compounds were non-genotoxic and antigenotoxic against H2O2-induced DNA damage with a positive dose-response effect and different inhibition percentages (the highest value: 95% for DADS) at all tested concentrations. Daily intake of Allium vegetables, DADS, or DPDS had no positive effects on flies’ lifespan and health span. Garlic and DADS exerted the highest cytotoxic effects in a positive dose-dependent manner. Garlic and DADS exerted a DNA-internucleosomal fragmentation as an index of induced proapoptotic activity on HL60 cells. Allium vegetables and DADS were able to induce clastogenic strand breaks in the DNA of HL60 cells. This study showed the genomic safety of the assayed substances and their protective genetic effects against the hydrogen peroxide genotoxine. Long-term treatments during the whole life of the Drosophila genetic model were beneficial only at low-median concentrations. The chemo-preventive activity of garlic could be associated with its distinctive organosulfur DADS. We suggest that supplementary studies are needed to clarify the cell death pathway against garlic and DADS.

The curative effect of Cymbopogon citrates volatile oil against chlorambucil drug toxicity

Chlorambucil (CLB) is a bifunctional alkylating drug widely used as an anticancer agent and immunosuppressant. CLB mutagenicity, teratogenicity, and carcinogenicity are indicated based on their structure and clinical history. This study aims to evaluate the antigenotoxic effect of Cymbopogon citratus essential oil, CC, (75 mg/kg) against CLB (7.5 mg/kg) genotoxicity in rats. GC/MS for essential oil has identified 19 compounds representing approximately 99.7% Geranial was the most abundant (53.5%) followed by Neral (35%) and Myrcene (5.3%). The lowest was α-Muurolene (0. 1%). The marked damage was observed in total genomic DNA and total protein profile of CLB-intoxicated rat's spleen tissues. Lymphocytes single-strand breaks of treated rats were examined by comet assay after CC had ameliorated these effects in a time-dependent manner (5, 10, and 15 days) for spleen and after 48 hours for lymphocytes. In conclusion, this study suggests that Cymbopogon citrates oil possesses antigenotoxic potential in CLB-intoxicated rats. It can constitute natural, new, and safe co-therapeutics.

Potential of Whole Pequi (Caryocar spp.) Fruit-Pulp, Almond, Oil, and Shell-as a Medicinal Food.

Pequi (Caryocar) pulp, the most consumed component of pequi fruit, is one of the richest Brazilian carotenoid sources, and the most important carotenoid food source native to the Cerrado. However, there are considerable differences among pequi species regarding total carotenoids content and carotenoids profile. Caryocar brasiliense Camb. pulp presents higher content of total carotenoids than Caryocar villosum (Aubl.) Pers. Regarding the carotenoids profile, few studies are available in the literature, mainly with C. brasiliense. Pequi pulp also has high contents of lipids, dietary fiber, zinc, and magnesium, and is source of calcium and polyphenols. Pequi almond presents high energy, lipid, protein, dietary fiber, and ash contents. Pequi oil (pulp and almond) has high levels of monounsaturated fatty acids, especially oleic acid, and relatively high contents of saturated fatty acids, mainly palmitic. Pequi shell (exocarp and external mesocarp) is the largest component of the fruit and a solid residue of the pequi processing, which is rich in dietary fibers, including soluble fibers, and phenolic compounds, mostly gallic acid, ellagic acid, and quercetin. Pulp oil is the pequi byproduct most investigated in in vivo studies. Research with pequi pulp oil in animal models has shown antioxidant, anti-inflammatory, cardioprotective, hepatoprotective, antigenotoxic, and anticarcinogenic effects. In humans, there are evidences supporting anti-inflammatory, cardioprotective, and antigenotoxic effects. Studies on carotenoids profile of pequi pulp in different fruit species are recommended, and in vivo studies are necessary to better explore the potential health benefits of pequi fruit components, mainly the pequi pulp and shell.

Antigenotoxic effects of morin against lead induced genomic damage in cultured human peripheral blood lymphocytes.

Lead (Pb) is a well-known carcinogenic heavy metal. Exposure to Pb induces DNA damage by enhancing the generation of reactive oxygen species (ROS). One of the possible ways to shield DNA from this damage is to supply antioxidants that can remove free radicals generated by genotoxicants. Hence, the current study was designed to evaluate the antigenotoxic potential of a flavonoid compound; morin against Pb-induced genomic damage on cultured human peripheral blood lymphocytes (PBL). The effect of Pb or morin or their combination was evaluated on the DNA damage using comet and sister chromatid exchange (SCE) assays. The results indicated a significant (p<0.05) increase in the SCE frequency and various comet parameters in a dose-dependent manner upon treatment with lead as compared to control in cultured PBL. Supplementation of morin along with Pb effectively negated DNA damage as measured by SCE frequency and comet parameters. PRACTICAL APPLICATIONS: Results of our current study suggest that the DNA damage induced by genotoxicants can be overcome by co-treatment with natural antioxidants, found in dietary supplements such as vegetables and fruits.

Evaluation of in vitro and in vivo genotoxic and antigenotoxic effects of Rhus coriaria

Rhus coriaria has been important in the treatment of many diseases in traditional use. In this content, the genotoxic, antigenotoxic, and oxidative stress effects of methanol extract of R. coriaria (RCE) were investigated in this study. Two hundred fifty, 500, or 750 µg/mL concentrations of RCE were not found to have DNA damaging effect on pET22-b(+) plasmid and were unable to induce micronuclei in human lymphocytes (24 or 48 h treatment period). However, it did not inhibit the genotoxic effect of mitomycin-c (0.25 µg/mL). Cytotoxic effects of RCE were investigated using mitotic index (MI) and nuclear division index (NDI). Five hundred, 1000, and 2000 mg/kg concentrations of RCE did not induce chromosome aberrations in rat bone marrow cells for 12 or 24 h treatment period. In addition, 2000 mg/kg concentration of RCE showed an antigenotoxic effect by decreasing to genotoxic effect of 400 mg/kg urethane at 12 and 24 h treatment periods. RCE showed cytotoxic effects by significantly decreasing NDI. Moreover, RCE increased cytotoxic effect of Mitomycin C (MMC). However, RCE did not induce cytotoxicity in rat bone marrow cells. The highest concentration of RCE reduced total oxidant level in 12 h treatment. Interestingly, the lowest total oxidant level was found in rats blood treated with the lowest concentration RCE and urethane together. Thousand and 2000 mg/kg concentrations of RCE decreased total antioxidant levels of rat blood at 24 h treatment period. Our results showed that RCE possess cytotoxic effect in short-term treatments in vitro. However, it does not demonstrate genotoxic or cytotoxic effects in vivo.

Protective effects of phenolic acids on mercury-induced DNA damage in precision-cut kidney slices.

Objective(s):Precision-cut tissue slices are considered an organotypic 3D model widely used in biomedical research. The comet assay is an important screening test for early genotoxicity risk assessment that is mainly applied on in vitro models. The aim of the present study was to provide a 3D organ system for determination of genotoxicity using a modified method of the comet assay since the stromal components from the original tissue make this technique complicated.Materials and Methods:A modified comet assay technique was validated using precision-cut hamster kidney slices to analyze the antigenotoxic effect of the phenolic compounds caffeic acid, chlorogenic acid, and rosmarinic acid in tissue slices incubated with 15 µM HgCl2. Cytotoxicity of the phenolic compounds was studied in Vero cells, and by morphologic analysis in tissue slices co-incubated with HgCl2 and phenolic compounds. Results:A modification of the comet assay allows obtaining better and clear comet profiles for analysis. Non-cytotoxic concentrations of phenolic acids protected kidney tissue slices against mercury-induced DNA damage, and at the same time, were not nephrotoxic. The highest protection was provided by 3 µg/ml caffeic acid, although 6 µg/ml rosmarinic and 9 µg/ml chlorogenic acids also exhibited protective effects.Conclusion:This is the first time that a modification of the comet assay technique is reported as a tool to visualize the comets from kidney tissue slices in a clear and simple way. The phenolic compounds tested in this study provided protection against mercury-induced genotoxic damage in precision-cut kidney slices.

Usnic acid attenuates genomic instability in Chinese hamster ovary (CHO) cells as well as chemical-induced preneoplastic lesions in rat colon

ABSTRACTUsnic acid (UA) is one of the pharmacologically most important compounds produced by several lichen species. To better understand the mechanism of action (MOA) of this important substance, this study examined the genotoxicity attributed to UA and its influence on mutagens with varying MOA using the micronucleus (MN) test in Chinese hamster ovary cells (CHO). Additional experiments were conducted to investigate the effect of UA on colon carcinogenesis in Wistar rats employing the aberrant crypt focus (ACF) assay. In vitro studies showed a significant increase in the frequency of MN in cultures treated with the highest UA concentration tested (87.13 µM). In contrast, UA concentrations of 10.89, 21.78, or 43.56 µM produced an approximate 60% reduction in chromosomal damage induced by doxorubicin, hydrogen peroxide, and etoposide, indicating an antigenotoxic effect. In the ACF assay, male Wistar rats treated with different UA doses (3.125, 12.5, or 50 mg/kg b.w.) and with the carcinogen 1,2-dimethylhydrazine exhibited a significantly lower incidence of neoplastic lesions in the colon than animals treated only with the carcinogen. Data suggest that the MOA responsible for the chemopreventive effect of UA may be related to interaction with DNA topoisomerase II and/or the antioxidant potential of the compound.

In vitro genotoxic and antigenotoxic effects of cynarin

Ethnopharmacological relevanceCynarin is an artichoke phytochemical that possesses a variety of pharmacological features including free-radical scavenging and antioxidant activity. The origin of artichoke species appears to be Mediterranean region. Two of these species, globe artichoke (Cynara cardunculus var. scolymus L.) and cardoon (Cynara cardunculus var. altilis DC), are widely cultivated and consumed. This vegetable, as the basis of the mediterranean diet, has been used as herbal medicine for its therapeutic effects since ancient times. Therefore, this study was performed to determine genotoxic and antigenotoxic effects of cynarin against MMC (mitomycin C) and H2O2 (hydrogen peroxide) induced genomic instability using chromosome aberrations (CAs), sister chromatid exchanges (SCEs), micronucleus (MN), and comet assays in human lymphocytes. Materials and methodsLymphocytes obtained from two healthy volunteers (1 male and 1 female) were exposed to different concentrations of cynarin (12–194 μM) alone and the combination of cynarin and MMC (0.60 μM) or cynarin and H2O2 (100 μM, only for comet assay). ResultsCynarin alone did not induce significant genotoxic effect in the CA, SCE (except 194 μM), MN, and comet assays. The combination of some concentrations of cynarin and MMC decreased the frequency of CAs, SCEs and MN induced by MMC. Furthermore, the combination of cynarin and H2O2 reduced all comet parameters at all the concentrations compared to H2O2 alone. While the highest concentrations of cynarin significantly decreased mitotic index (MI), the combination of cynarin and MMC increased the reduction of MI induced by MMC alone. ConclusionAll the results obtained in this study demonstrated that cynarin exhibited antigenotoxic effects rather than genotoxic effects. It is believed that cynarin can act as a potential chemo-preventive against genotoxic agents.

Photoprotective and Antigenotoxic Effects of the Flavonoids Apigenin, Naringenin and Pinocembrin.

This work evaluated the photoprotective and antigenotoxic effects against ultraviolet B (UVB) radiation of flavonoid compounds apigenin, naringenin and pinocembrin. The photoprotective efficacy of these compounds was estimated using in vitro photoprotection indices, and the antigenotoxicity against UVB radiation was evaluated using the SOS chromotest and an enzymatic (proteinase K/T4 endonuclease V enzyme) comet assay in UV-treated Escherichia coli and human (HEK-293) cells, respectively. Naringenin and pinocembrin showed maximum UV-absorption peak in UVC and UVB zones, while apigenin showed UV-absorption capability from UVC to UVA range. These compounds acted as UV filters reducing UV-induced genotoxicity, both in bacteria and in human cells. The enzymatic comet assay resulted highly sensitive for detection of UVB-induced DNA damage in HEK-293 cells. In this work, the photoprotective potential of these flavonoids was widely discussed.

Anti-inflammatory and antioxidative properties of honey bee venom on Freund's Complete Adjuvant-induced arthritis model in rats

The aim of this study was to assess anti-inflammatory, anti-oxidant, anti-genotoxic and immunomodulatory effects of honey bee venom (HBV) on adjuvant-induced arthritis in rats. Thirty-five rats were equally divided into a negative control (NC), a positive control (PC) and low, moderate and high doses (2, 4 and 20 mg/kg, respectively) of HBV treatment groups. Freund's Complete Adjuvant (FCA) was given to the rats to form arthritis. The treatment groups were treated with HBV for 3 consecutive weeks. After the treatment, plasma IL-1β, IL-6, TNF-α, IFN-γ and TGF-β1, total oxidant status (TOS), total antioxidant status (TAS) and myeloperoxidase (MPO) activities and mononuclear leukocyte (MNL) DNA damage levels were measured. Oxidative stress index (OSI) was calculated. IL-1β, IL-6, TNF-α, TGF-β1, IFN-γ, TOS, OSI, DNA damage levels and MPO activities were significantly higher and TAS levels were lower in the PC group than the NC. After low-doses of HBV treatment IL-1β, IL-6, TNF-α, TGF-β1, TOS, OSI, MPO and MNL-DNA damage levels significantly decreased according to the PC, while IFN-γ and TAS levels increased. The differences in moderate and high-dose HBV treatment groups were not as significant as low HBV doses. Low-doses of HBV has been shown to treat RA with anti-inflammatory and antioxidant effects, by preventing DNA damage. However, these effects have not been observed as strong at higher doses of HBV. In summary, HBV may be an effective option to ameliorate RA, but the optimization of the therapeutic dose has a crucial role.

Antioxidant, antiapoptotic, antigenotoxic, and hepatic ameliorative effects of L-carnitine and selenium on cadmium-induced hepatotoxicity and alterations in liver cell structure in male mice

L-carnitine (LC) and selenium (Se) have significant protective and antioxidant effects on several tissues. Cadmium (Cd), widely used in some industries and emitted from fossil fuels, is a heavy metal having a number of side effects, including hepatotoxicity. This study aims to assess the ameliorative function of both LC and SeCl4 on cadmium chloride (CdCl2)-induced liver toxicity. In total, 70 male mice included in this study were allocated to seven groups: control, CdCl2, LC, SeCl4, CdCl2 plus SeCl4, CdCl2 plus LC, CdCl2 plus SeCl4 and LC groups. Hepatic aminotransferase (aspartate aminotransferase [AST] and alanine transaminase [ALT]) activity and tumor necrosis factor-alpha [TNF-α] levels, as well as the antioxidant biomarkers (superoxide dismutase [SOD], glutathione reductase [GRx], glutathione-S-transferase [GST] and catalase [CAT], were examined. Histological and transmission electron microscopic [TEM] variations in the liver were used as indicators of liver damage after the administration of CdCl2-alone or CdCl2 with LC, SeCl4, or both. Genotoxic effects of CdCl2 were also evaluated and the possible roles of SeCl4 and/or LC on the expression of the antioxidant enzymes were studied. Results showed that administration of LC and SeCl4 decreased CdCl2-induced increase in ALT and AST levels and reduced oxidative stress to normal levels. In addition, LC combined with SeCl4 had a highly synergistic effect and elevated significantly the enzymatic antioxidants and decreased lipid peroxidation levels compared with those in the CdCl2-treated group. It is clear from the data that both LC and SeCl4 inhibit liver injury and improve the redox state in mice.