Antigenotoxic effect of hyperoside against Mitomycin C and hydrogen peroxide-induced genotoxic damage on human lymphocytes

Hyperoside is a flavonol glycoside isolated from various plant genera such as Hypericum and Crataegus. It has an important place in the human diet and is used medically to relieve pain and ameliorate cardiovascular functions. However, a comprehensive profile of the genotoxic and antigenotoxic effects of hyperoside is not known. The current study aimed to investigate the genotoxic and antigenotoxic effects of hyperoside against genetic damages induced by two genotoxins (MMC and H₂O₂) using chromosomal aberrations (CAs), sister chromatid exchanges (SCEs), and micronucleus (MN) assays in human peripheral blood lymphocytes in vitro. Blood lymphocytes were incubated with 7.8–62.5 μg/mL concentrations of hyperoside alone and simultaneously with 0.20 μg/mL Mitomycin C (MMC) or 100 μM Hydrogen peroxide (H₂O₂). Hyperoside did not exhibit genotoxic potential in the CA, SCE, and MN assays. Moreover, it did not cause a decrease in mitotic index (MI) which is an indicator of cytotoxicity. On the other hand, hyperoside significantly decreased CA, SCE, and MN (except for MMC treatment) frequencies induced by MMC and H₂O₂. Hyperoside, increased mitotic index against both mutagenic agents at 24-h treatment when compared to positive control. Our results demonstrate that hyperoside exhibited antigenotoxic effects rather than genotoxic in vitro human lymphocytes. Therefore, hyperoside may be a potential preventive agent in inhibiting chromosomal and oxidative damage induced by genotoxic chemicals.     

50% Ethanol extract of Orthosiphon stamineus modulates genotoxicity and clastogenicity induced by mitomycin C

Herbal products contain a variety of compounds which may be useful in protecting against cellular damage caused by mutagens. Orthosiphon stamineus (O.s) also known as Cat whiskers. The herb has been shown anti-oxidative properties and can modulate key cellular proteins that have cytoprotective effect. The study aimed to evaluate the effects of different doses (250, 500 and 1000?mg?kg^?1) of 50% ethanol extract of O.s (Et. O.s) on micro-nucleated polychromatic erythrocytes (MNPCE), Polychromatic to normachromatic erythrocytes ratio (PCE/NCE), Mitotic index (MI), and Chromosomal aberration (CA) in Bab/c mice. Moreover, these parameters were used to evaluate the anti-genotoxic and clastogenic potencies of (Et. O.s) against mitomycin c (MMC) that interact with biological molecules and induce genotoxic and clastogenic disorders in non-tumor cells. MMC (4?mg?kg^?1) was injected intraperitoneally (i.p.) to the mice before and after treatment with three different doses of (Et. O.s). The results indicated that the extract at different doses did not show significant (p?≥?0.05) differences in (MNPCE), (PCE/NCE) ratios, and (CA) values. The higher doses sowed high (MI) values compared with untreated control group. MMC showed significant increase (p?≤?0.001) in (MNPCE), (CA) and reduce (PCE/NCE) and (MI) values compared with untreated control group. Treatment with (Et. O.s) at different doses before and after MMC injection showed to modulate MNPCE, PCE/NCE ratios, CA and MI values in mice bone marrow cells suggesting genoprotective potential of this plant extract.     

Cytogenetic and hematological alterations induced by acute oral exposure of imidacloprid in female mice

Imidacloprid (IMD), 1(6-chloro-3-pyridinyl)methyl)-N-nitro-2-imidazolidinimine, was administered in female mice to study in vivo cytogenetic (chromosomal aberrations (CAs) and micronucleus assay) and hematological effects. The acute oral LD₅₀ was determined to be 150?mg/kg bw in mice following OECD guidelines using AOT StatPgm425 software. The mice were administered orally with distilled water (negative control); mitomycin C (MMC), 1?mg/kg (positive control) and sub-lethal doses of 37.5 (low), 75.0 (medium) and 112.5 (high) mg/kg bw (25%, 50% and 75% of LD₅₀) of IMD to analyze CAs and hematological effects after 24?h, whereas micronucleus test (MT) after 48?h. The genotoxicity analysis revealed that selected test doses of IMD – medium and high doses – induced significantly mitotic inhibition (p?<?0.01), CAs (p?<?0.01) and at high dose micronucleus (MN) formation (p?<?0.05). Significant changes in red blood cell (RBC; p?<?0.01), hemoglobin (Hb; p?<?0.01) and erythrocyte sedimentation rate (ESR; p?<?0.001) were observed, except WBC in which significant increase (p?<?0.001) was observed. Present observation substantiates overall significant dose dependent genotoxic potential (p?<?0.05; r?=?0.98) of IMD. Precautions should be taken to minimize possible risk to exposed farmers of the state of Haryana (India) – an agrarian economy.     

Evaluation of the antimutagenic,antigenotoxic, and antioxidant activities of Eriobotrya japonica leaves

Abstract

Context: The leaves of Eriobotrya japonica (Thunb.) Lindl. (Rosaceae) are used in traditional medicine to treat inflammatory diseases. However, information about the antigenotoxic and antioxidant properties of its leaves remains to be elucidated.

Objective: The objective of this work was to evaluate the mutagenic/antimutagenic, genotoxic/antigenotoxic, and antioxidant potentials of aqueous and total oligomers flavonoid (TOF) extracts from E. japonica.

Materials and methods: The mutagenic/antimutagenic and genotoxic/antigenotoxic potentials of extracts (50, 250, and 500?µg/plate) were evaluated, respectively, by the Ames test with 48?h incubation and the SOS chromotest test with 2?h incubation. The antioxidant capacity of these extracts (ranging from 50 to 700?µg/mL) was tested using xanthine/xanthine oxidase and the deoxyribose assays.

Results: Eriobotrya japonica extracts showed neither mutagenic nor genotoxic effect. The highest protective effect against methyl methanesulfonate and 2-aminoanthracene was obtained in the presence of aqueous extract, with IC₅₀ values of 80 and 140?µg/plate, respectively, against S. typhimurium TA104. Moreover, this extract (500?µg/plate) was also able to reduce significantly the genotoxicity induced by nitrofurantoin and aflatoxin B1 with IC₅₀ values of 140 and 240?µg/assay, respectively. Likewise, aqueous and TOF extracts inhibited xanthine oxidase and superoxide anion formation with IC₅₀ values ranging from 45 to 95 and from 70 to 90?µg/mL, respectively. However, TOF extract is more efficient in inhibiting hydroxyl radical and chelating iron ion with IC₅₀ values of 140 and 400?µg/mL, respectively, when compared with the aqueous extract.

Conclusion: Eriobotrya japonica prevents the genotoxicity of some carcinogenic substances probably thanks to its antioxidant capacities.     

In vitro genotoxic and antigenotoxic effects of an exopolysaccharide isolated from Lactobacillus salivarius KC27L

Exopolysaccharide isolated from Lactobacillus salivarius (new genus name Ligilactobacillus) KC27L strain (EPS_KC27L) exhibits antioxidant properties with 1,1-diphenyl-2-picrylhydrazase (DPPH) radical and superoxide anion radical (O₂^-.) scavenging effect and iron ion (Fe²⁺) chelating activity. This study aimed to investigate the in vitro genotoxic effects of EPS_KC27L alone (12.50, 25.00, 50.00, and 100.00 μg/mL) and its antigenotoxic activity against DNA damage induced by mitomycin-C (MMC; 0.20 μg/mL), methyl methanesulfonate (MMS; 5.00 μg/mL), and hydrogen peroxide (H₂O₂; 100 μM). For this purpose, chromosome aberration (CA), sister chromatid exchange (SCE), micronucleus (MN), and comet assays were performed in human peripheral lymphocytes. In addition, the structure of EPS_KC27L was investigated in the scanning electron microscope (SEM). EPS_KC27L alone did not cause a significant genotoxic effect in CA, SCE, MN, and comet tests. EPS_KC27L significantly decreased the frequency of CA, SCE, and MN induced by MMC and MMS. EPS_KC27L also significantly reduced DNA damage induced by H₂O₂. This study showed that the EPS_KC27L alone has no genotoxic risk at these concentrations and shows antigenotoxic activity against MMC, MMS, and H₂O₂. Consequently, EPS_KC27L was found to exhibit chemopreventive activity against genotoxic agents. This effect is believed to be due to the antioxidant properties of EPS_KC27L.     

The genotoxic and antigenotoxic effects of Salvia fruticosa leaf extract in human blood lymphocytes

Abstract

The aim of this study was to investigate the genotoxic and antigenotoxic effects of Salvia fruticosa (Sf) leaf extract with the absence and presence of S9 mix using sister chromatid exchange (SCE), chromosome aberration (CA) and micronucleus (MN) formation test systems in human peripheral blood lymphocytes (HPBLs) that were treated with 1.5-, 3.0- and 6.0-µL/mL concentrations for 24- and 48-hour treatment periods. The cytotoxicity of Sf leaf extract was also investigated by calculating the mitotic index (MI), proliferation index (PI) and nuclear division index (NDI). In the absence of S9 mix, Sf leaf extract alone increased SCE frequency at the 48-hour treatment period; however, it induced the CA and MN at all concentrations and at all treatment periods. Sf plus MMC (mitomycin C) synergically induced SCE and CA, except the highest concentration of Sf leaf extract and MMC on induction of SCE. In addition, Sf leaf extract induced the effect of MMC on MN frequency for 24 hours, but it significantly decreased the effect of MMC on MN frequency for the 48-hour treatment period. Sf leaf extract showed a cytotoxic effect by decreasing the MI; however, it did not decrease the PI and NDI. In the presence of S9 mix, Sf leaf extract did not increase the SCE, when compared to solvent control, whereas it reduced the effect of cyclophosphamide (Cyp). Sf leaf extract induced the CA and MN, but could not increase the effect of Cyp on CA and MN formation. Sf leaf extract had no cytotoxic effect; however, it induced the cytotoxicity of Cyp.     

Assessment of combinations of antiandrogenic compounds vinclozolin and flutamide in a yeast based reporter assay

Glycyrrhiza glabra Linn. (licorice) is widespread throughout the Mediterranean region and certain areas of Asia. Historically, the dried rhizome and root of the plant were used by the Chinese, Egyptian, Greek, Indian, and Roman civilizations as expectorant and carminative. In the modern medicinal system, licorice is used to treat liver ailments, dyspepsia, bronchitis, rheumatoid arthritis etc. Despite the extensive pharmacological applications, the genotoxic potential of G. glabra extract (GutGard™) has not been evaluated. Hence, this study was conducted to investigate the genotoxic potential of GutGard™ using battery of in vitro test systems: bacterial reverse mutation test (Ames II™), chromosome aberration (CA) and micronucleus (MN) tests. GutGard™ did not show significant increase in number of revertant colonies in Salmonella typhimurium strains (TA98 and TAMix) with/without S9 fraction. In CA and MN studies, GutGard™ did not show clastogenic effect at 4 and 18 h treatments with and without S9 fraction. Results indicated that GutGard™ is not mutagenic in a battery of genotoxicity tests.     

Evaluation of DNA damage induced by norcantharidin in human cultured lymphocytes

Norcantharidin (NCTD) is currently used in the treatment of several cancers such as leukemia, melanoma and hepatoma. The mechanism of action of NCTD is suggested to involve induction of apoptosis of cancer cells via production of reactive oxygen species. In this study, the genotoxic effect of different concentrations of NCTD (1, 10 and 20?μm) in human lymphocytes was investigated using sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) assays. The results revealed that NCTD significantly increased the rate of SCEs (p?<?0.05) in a dose-dependent manner. In addition, NCTD significantly increased the number of high-frequency cells (SCEs?≥?8, p?<?0.05). However, NCTD did not have any significant effect on the rate of CAs (p?>?0.05). In addition, no significant differences were detected in the mitotic index or proliferative index at examined doses (up to 20?μm). In conclusion, NCTD is genotoxic to human cultured lymphocytes as measured by SCE assay.     

In vitro cytotoxicity,genotoxicity and antigenotoxicity assessment of Solanum lycocarpum hydroalcoholic extract

Context: Solanum lycocarpum A. St.-Hil. (Solanaceae), popularly known as ‘fruta-do-lobo’ (wolf fruit), ‘lobeira’ and ‘jurubebão’, is commonly used by native people of Central Brazil in powder form or as a hydroalcoholic extract for the management of diabetes and obesity and to decrease cholesterol levels. Objective: The present study determines the possible cytotoxic, genotoxic and antigenotoxic activities of hydroalcoholic extract of the S. lycocarpum fruits (SL).

Materials and methods: The clonogenic efficiency assay was used to determine the cytotoxicity. Three concentrations of SL (16, 32 and 64?μg/mL) were used for the evaluation of its genotoxic and antigenotoxic potential on V79 cells using the micronucleus and comet assays. In the antigenotoxicity assays, the cells were treated simultaneously with SL and the alkylating agent methyl methanesulphonate (MMS, 44?μg/mL for the micronucleus assay and 22?μg/mL for the comet assay) as an inducer of micronuclei and DNA damage.

Results: The results showed that SL was cytotoxic at concentrations up to 64?μg/mL. No significant differences in the rate of chromosome or DNA damage were observed between cultures treated with SL and the control group. In addition, the frequencies of micronuclei and DNA damage induced by MMS were significantly reduced after treatment with SL. The damage reduction percentage ranged from 68.1% to 79.2% and 12.1% to 16.5% for micronucleus and comet assays, respectively.

Discussion and conclusion: SL exerted no genotoxic effect and exhibited chemopreventive activity against both genomic and chromosome damage induced by MMS.     

Antimalarial,antiplasmodial and analgesic activities of root extract of Alchornea laxiflora

Context: Alchornea laxiflora (Benth.) Pax. &; Hoffman (Euphorbiaceae) root decoctions are traditionally used in the treatment of malaria and pain in Nigeria.

Objective: To assess the antimalarial, antiplasmodial and analgesic potentials of root extract and fractions against malarial infections and chemically-induced pains.

Material and methods: The root extract and fractions of Alchornea laxiflora were investigated for antimalarial activity against Plasmodium berghei infection in mice, antiplasmodial activity against chloroquine sensitive (Pf 3D7) and resistant (Pf INDO) strains of Plasmodium falciparum using SYBR green assay method and analgesic activity against experimentally-induced pain models. Acute toxicity study of the extract, cytotoxic activity against HeLa cells and GCMS analysis of the active fraction were carried out.

Results: The root extract (75–225?mg/kg, p.o.) with LD₅₀ of 748.33?mg/kg exerted significant (p?P. berghei infection in suppressive, prophylactive and curative tests. The root extract and fractions also exerted moderate activity against chloroquine sensitive (Pf 3D7) and resistant (Pf INDO) strains of P. falciparum with the ethyl acetate fraction exerting the highest activity with IC₅₀ value of 38.44?±?0.89?μg/mL (Pf 3D7) and 40.17?±?0.78?μg/mL (Pf INDO). The crude extract was not cytotoxic to HeLa cells with LC₅₀ value >100?μg/mL. The crude extract and ethyl acetate fraction exerted significant (p?Discussion and conclusions: These results suggest that the root extract/fractions of A. laxiflora possess antimalarial, antiplasmodial and analgesic potentials and these justify its use in ethnomedicine to treat malaria and pain.     

Evaluation of vitamin B12 effects on DNA damage induced by paclitaxel

Abstract

Paclitaxel (PAC) is an anticancer drug that has been shown to generate free radicals leading to irreversible cell injury. Vitamin B12 has antioxidative properties and can protect DNA from free radicals. In this study, we examined the possible genotoxic effect of PAC on DNA as well as the possible protective effect of vitamin B12 on DNA damage induced by paclitaxel. Sister chromatid exchanges (SCEs), chromosomal aberrations (CAs) and 8-hydroxy-2’-deoxyguanosine (8-OHdG) levels were measured in cultured human blood lymphocytes treated with PAC (10?µM) and/or vitamin B12 (2.7?mg/mL). Our results showed that PAC significantly increased the frequencies of SCEs (p?<?0.001) and CAs (p?<?0.001) in human blood lymphocytes, as compared to controls. These DNA damages, caused by PAC drug, were prevented by pretreatment of cells with vitamin B12. In addition, we showed that PAC induced an increase in 8-OHdG, a marker of oxidative DNA damage, and that this increase was prevented by vitamin B12. Vitamin B12 seems to protect against genotoxicity induced by PAC in human blood lymphocytes.     

In vitro antioxidant and anti-cholinesterase activities of Rhizophora mucronata

Context: Rhizophora mucronata Lam. (Rhizophoraceae), commonly known as Asiatic mangrove, has been used traditionally among Asian countries as folk medicine.

Objective: This study investigates the cholinesterase inhibitory potential and antioxidant activities of R. mucronata.

Materials and method: Rhizophora mucronata leaves were successively extracted using solvents of varying polarity and a dosage of 100–500?µg/ml were used for each assay. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities were assessed according to the method of Ellman. In vitro antioxidant activity was assessed using free radical scavenging, reducing power, and metal-chelating activity (duration – 3 months). Total phenolic and flavonoid content were quantified spectrophotometrically. Compound characterization was done using column chromatography, NMR, FTIR, and LC-MS analysis.

Results: Methanolic leaf extract (500?µg/ml) exhibited the highest inhibitory activity against AChE (92.73?±?0.54%) and BuChE (98.98?±?0.17%), with an IC₅₀ value of 59.31?±?0.35 and 51.72?±?0.33?µg/ml, respectively. Among the different solvent extracts, methanolic extract exhibited the highest antioxidant activity with an IC₅₀ value of 47.39?±?0.43, 401.45?±?18.52, 80.23?±?0.70, and 316.47?±?3.56?µg/ml for DPPH, hydroxyl, nitric oxide radical, and hydrogen peroxide, respectively. Total polyphenolic and flavonoid contents in methanolic extract were observed to be 598.13?±?1.85?µg of gallic acid equivalent and 48.85?±?0.70?μg of rutin equivalent/mg of extract. Compound characterization illustrated (+)-catechin as the bioactive compound responsible for cholinesterase inhibitory and antioxidant activities.

Conclusion: The presence of rich source of flavonoids, in particular catechin, might be responsible for its cholinesterase inhibitory and antioxidant activities.     

Evaluation of genotoxic and antigenotoxic effects of boron by the somatic mutation and recombination test (SMART) on Drosophila

Objective: In this study, different concentrations of boron have been evaluated for genotoxic and antigenotoxic properties by using the somatic mutation and recombination test (SMART) on Drosophila melanogaster. Study Design: The treatment concentrations were chosen to a pretest. Third-instar larvae trans-heterozygous for two genetic markers, multiple wing hair (mwh) and flare (flr3), were treated at different concentrations (0.1, 5, 10, 20, and 40?mg/mL) of boron. In addition to investigating antigenotoxic effects, the same boron concentrations were co-administered with 0.1?mM Ethyl Methane Sulfonate (EMS). Distilled water was used as a negative control; 0.1?mM of EMS was used as a positive control. For the chronic feeding study, small plastic vials were prepared with 1.5?g of dry Drosophila Instant Medium and 5?mL of the respective test solution. Hundreds of trans-heterozygous larvae were embedded into this medium. Feeding ended with pupation of the surviving larvae. After metamorphosis, all surviving flies were collected and stored in a 70% ethanol solution. Preparation and microscopic analyses of wing were made after the treatment. Then the observed mutations were classified according to size and type of mutation per wing. Results: Results indicated that there is no significant genotoxic effect with all of the boron concentrations. In addition, the antigenotoxic activities of boron against EMS were tested. Results indicated that all boron concentrations (0.1, 5, 10, 20 and 40?mg/mL) were able to abolish the genotoxic effects induced by the EMS. Conclusion: It is suggested that the observed effects can be linked to the antioxidant properties of boron. Moreover, these in vivo results will contribute to the antigenotoxicity database of boron.     

Protective effects of Scutellaria lindbergii root extract against oxidative-induced cell and DNA damage in mouse fibroblast-like cells

Context: Scutellaria lindbergii Rech. f. (Lamiaceae) is an Iranian species of Scutellaria which has been shown to exert antimicrobial, antioxidant and cytotoxic effects. Objective: The protective properties of total methanol extract (TME) of S. lindbergii and its fractions (defatted and CH₂Cl₂) were investigated against cytotoxic and genotoxic effects of H₂O₂ in NIH 3T3 cell line as non-malignant cells. Materials and methods: The cells were incubated with different concentrations of S. lindbergii root extracts [TME (15–250?μg ml^?1), defatted fraction (15–500?μg ml^?1) and CH₂Cl₂ fraction (5–40?μg ml^?1)] and toxic concentration of H₂O₂ (200?µM) at 37?°C for 2?h concurrently and Cell viability was quantitated by MTT assay. The antigenotoxic effect of extracts was investigated using comet assay. The cells were incubated with extracts [TME (25–250?μg ml^?1), defatted fraction (25–500?μg ml^?1) and CH₂Cl₂ fraction (5–40?μg ml^?1)] and H₂O₂ (25?µM) at 4?°C for 20?min, then the comet assay was performed. DNA damage was expressed as percentage tail DNA. Results: Total methanol extract of S. lindbergii and its fractions had a significant inhibitory effect on DNA damage. The IC₅₀ values of TME, defatted fraction and CH₂Cl₂ fraction against DNA damage were determined as 48, 138 and 8?μg ml^?1, respectively. Conclusion: S. lindbergii extracts can prevent oxidative DNA damage, which is likely due to its flavonoids and phenolic compounds as antioxidant constituents.     

Hepatoprotective activity of Feronia limonia root

Objectives The aim of this study was to evaluate the hepatoprotective potential of a methanolic extract and of marmesin isolated from the root bark of Feronia limonia. Methods Activity levels of aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT), cell viability and cell death were evaluated in HepG2 cells (human liver hepatoma cells) treated with CCl₄ in the presence or absence of F. limonia extract or marmesin. Plasma activity levels of AST, ALT, bilirubin, alkaline phosphatase, protein, hepatic antioxidants, lipid peroxidation and histopathological evaluations were carried out in rats treated with CCl₄ alone or co‐supplemented with F. limonia extract or marmesin in a dose‐dependent manner. Key findings In‐vitro co‐supplementation of F. limonia methanolic extract or marmesin significantly minimized alteration in levels of AST and ALT and improved cell viability. Oral administration of F. limonia methanolic extract or marmesin significantly prevented CCl₄‐induced elevation in the plasma markers of hepatic damage and hepatic lipid peroxidation and a decrease in hepatic antioxidants. In‐vivo hepatoprotective potential of F. limonia methanolic extract and marmesin was evident from the minimal alterations in the histoarchitecture of liver. Conclusions This has been the first scientific report on the hepatoprotective potential of F. limonia root bark methanolic extract and marmesin.     

Hyparrhenia hirta: A potential protective agent against hematotoxicity and genotoxicity of sodium nitrate in adult rats

The present study was carried out to examine the adverse hematotoxic and genotoxic effects of water nitrate pollution on male adult rats and the use of hyparrhenia hirta methanolic extract in alleviating these effects. Sodium nitrate (NaNO₃) was administered to adult rats by oral gavage at a dose of 400 mg kg^?1 bw daily for 50 days, while hyparrhenia hirta methanolic extract was given by drinking water at a dose of 1.5 mg mL^?1 (200 mg kg^?1 bw). The NaNO₃‐treated group showed a significant decrease in red blood cell count, hemoglobin and hematocrit and a significant increase in total white blood cell, in neutrophil and eosinophil counts. Platelet count, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration remained unchanged in treated groups compared to those of controls. Meanwhile, the results showed a marked reduction in the antioxidant enzyme activities, such as superoxide dismutase, catalase, and glutathione peroxidase, along with an elevation in the level of lipid peroxidation and a reduction in the total glutathione content, indicating the induction of oxidative stress in the erythrocytes of NaNO₃‐treated group. Interestingly, NaNO₃ treatment showed a significant increase in the frequencies of total chromosomal aberrations, aberrant metaphases and micronucleus in bone‐marrow cells. The oxidative stress induced by nitrate treatment might be the major cause for chromosomal rearrangements as free radicals leading to DNA damage. Hyparrhenia hirta methanolic extract appeared to be effective against hematotoxic and genotoxic changes induced by nitrate, as evidenced by the improvement of the markers cited above. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 1275–1284, 2015.     

Vitamin E protects human lymphocytes from genotoxicity induced by oxaliplatin

Oxaliplatin is a platinum-based anticancer drug that has been shown to be genotoxic to the normal cells. Vitamin E is a potent antioxidant that may protect and enhance the repair of the damaged DNA. In this study, we aimed to evaluate the genotoxic effect of oxaliplatin on DNA by measuring the frequency of chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) in cultured human lymphocytes. We also attempted to explore the potential protective effect of vitamin E on chromosomal damage induced by oxaliplatin. Results showed that oxaliplatin significantly increased the frequency of CAs (p?<?0.001) and SCEs (p?<?0.001) as compared to control. This chromosomal damage, caused by oxaliplatin, was significantly decreased by pretreatment of cells with vitamin E. Moreover, the results showed that oxaliplatin caused a significant reduction in the cell kinetic parameters, the mitotic index (MI) and the proliferative index (PI). However, vitamin E did not affect this reduction in the MI and PI. Therefore, we conclude that oxaliplatin is genotoxic, and vitamin E can prevent the chromosomal damage induced by oxaliplatin but it has no effect on oxaliplatin-induced cytotoxicity.     

Pharmacological study on Panax ginseng C. A. Meyer. XIV. Effect of 70% methanolic extract from red ginseng on the cytocidal effect of mitomycin c against rat ascites hepatoma AH 130]

The influence of the 70% methanolic extract (RMe) from Red Ginseng (a steamed and dried root of Panax ginseng C. A. Meyer) on the antitumor activity of mitomycin C (MMC) against rat ascites hepatoma AH 130 was investigated. In the case of a solid tumor, RMe at oral doses of 200, 500 mg/kg showed an inhibitory effect, but RMe was ineffective in the case of an ascites tumor. MMC combined with RMe showed a stronger antitumor effect than MMC alone. Moreover, RMe inhibited the pulmonary metastases of the tumor cells, as well as the decrease of blood platelet counts and of the fibrinogen level induced by the infusion of the tumor cells in rats. Furthermore, RMe promoted the uptake of MMC into the tumor cells and enhanced in vitro the cytotoxicity of MMC against the cultured tumor cells.     

Pharmacological study on Panax ginseng C. A. Meyer. XV. Effects of 70% methanolic extract from red and white ginseng on the antitumor activity of mitomycin C]

The influence of various fractions and ginsenosides from the 70% methanolic extract (RMe) of Red Ginseng (a steamed and dried root of Panax ginseng C. A. Meyer) on the cytocidal effect of mitomycin C (MMC) against Ehrlich ascites carcinoma was investigated in vitro. The AcOEt soluble portion (RMe-I) showed an increasing effect on the activities of lysosomal enzymes in the cultured tumor cells. RMe-I promoted the uptake of MMC into the tumor cells and enhanced the cytotoxicity of MMC against the cultured tumor cells. 20(S)-, 20(R)-ginsenoside Rg3 and ginsenoside Rh2 isolated from RMe-I promoted the uptake of MMC into the tumor cells but ginsenosides from the n-BuOH soluble portion (RME-II) had no effect. Furthermore, the influence of RMe and the 70% methanolic extract (WMe) from White Ginseng (a dried root of Panax ginseng C. A. Meyer) on the cytocidal effect of MMC was investigated in vivo. MMC combined with RMe showed stronger antitumor effects against the ascites form of mouse Ehrlich ascites carcinoma and rat ascites hepatoma AH 130 than MMC combined with WMe. The activities of lysosomal enzymes in tumor cells were also more increased in comparison with that combined MMC and WMe.     

Antigenotoxic effects of ascorbic acid against megestrol acetate-induced genotoxicity in mice

The genotoxicity of megestrol acetate was studied in mouse bone marrow cells using sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) as parameters. Megestrol acetate (8.12, 16.25 and 32.50 mg/ kg of body weight) was injected intraperitoneally separately in different groups of animals. Both CAs and SCEs were statistically increased at 16.25 and 32.50 mg/kg of body weight. Our earlier in vitro studies show the generation of free oxygen radicals, by synthetic progestins responsible for the genotoxic damage. As the genotoxic effects of steroids can be reduced by natural products having antioxidant properties, and ascorbic acid possesses antioxidant activity, ascorbic acid (20, 40 or 60 mg/kg of body weight) administered together with megestrol acetate (32.50 mg/kg of body weight) significantly decreased CAs and SCEs, suggesting an antigenotoxic role of ascorbic acid against megestrol acetate-induced genotoxic damage in mice bone marrow cells. The antigenotoxic effect was clearly dose dependent. The highest protective effect was observed at 60 mg/kg body weight of ascorbic acid treated with 32.50 mg/kg body weight of megestrol acetate.