Mouse Micronucleus Test Research Articles

Jaboticaba peel: Antioxidant compounds, antiproliferative and antimutagenic activities

This paper reports on the anthocyanin and antioxidant contents, an the ‘in vitro’ antiproliferative and ‘in vivo’ mutagenic/antimutagenic activities of freeze-dried jaboticaba peel (JP). According to the proximate composition, JP showed a high dietary fiber content. The identification and quantification of the JP anthocyanins was carried out by HPLC-PDA and LC–MS/MS, which revealed the presence of two compounds: delphinidin 3-glucoside and cyanidin 3-glucoside (634.75 and 1963.57mg 100g−1 d. w., respectively). JP showed a strong antioxidant potential: 25,514.24±3037μM TEg−1, 45.38±0.50μgmL−1 and 9458±97μM TEACg−1, for ORAC, DPPH and ABTS, respectively. The polar JP extract demonstrated antiproliferative effects against leukemia (K-562), and the non-polar extract was the most active against prostate cancer cell (PC-3), according to the antiproliferative assay. The micronucleus test in mice demonstrated that the polar JP extract induced no DNA damage and hence it showed no cytotoxic properties on mice bone marrow cells and caused no mutagenic effects.

Scientific Opinion on the safety evaluation of the substance, 2‐phenyl‐3, 3‐bis(4‐hydroxyphenyl)phthalimidine, CAS No. 6607–41‐6, for use in food contact materials

This scientific opinion of EFSA deals with the risk assessment of the substance 2-phenyl-3, 3-bis(4-hydroxyphenyl)phthalimidine with the CAS No. 6607–41-6 and the FCM substance No 872, for use as a co-monomer for manufacturing polycarbonate polymers intended to be used for single and repeated contacts with all kinds of foodstuffs without restriction in time and temperature. Based on three in vitro genotoxicity tests and a mouse micronucleus test in vivo on the substance, the Panel considered that there is no concern with respect to genotoxicity of the substance. The CEF Panel concluded that there is no safety concern for the consumer if 2-phenyl-3, 3-bis(4-hydroxyphenyl)phthalimidine is used as a co-monomer in polycarbonate copolymer and its migration does not exceed 0.05 mg/kg food. Potential migration of aniline, an impurity of the substance, should be in compliance with the restriction set in the Commission Regulation (EU) No 10/2011, i.e. not detectable.

Genotoxicity of Zizyphi Spinosi Semen in Bacterial Reverse Mutation (Ames) Test, Chromosomal Aberration and Micronucleus Test in Mice

Zizyphi spinosi semen (Z. spinosi) has been used in traditional Chinese medicine for the treatment of rheumatoid arthritis and wounds. However, toxicity in high doses was often observed due to the presence of alka- loids. This study was conducted to investigate the potential genotoxicity of Z. spinosi in vitro and in vivo. This was examined by the Bacterial reverse mutation (Ames) test using Salmonella typhimurium TA98, TA100, TA1535, TA1537 and Escherichia coli WP2uvrA, Chromosomal aberration was investigated using Chinese hamster lung cells and the micronucleus test using mice. Z. Spinosi did not induce mutagenicity in the Ames test, and it did not produce chromosomal aberration in Chinese hamster lung cells with and without metabolic activation, nor in the micronucle- ated polychromatic erythrocytes in the bone marrow cells in mice. Based on these results, it is concluded that Z. spi- nosi does not have mutagenic potential under the conditions examined in each study.

Genotoxicity profile of fexinidazole--a drug candidate in clinical development for human African trypanomiasis (sleeping sickness)

The parasitic disease human African trypanomiasis (HAT), also known as sleeping sickness, is a highly neglected fatal condition endemic in sub-Saharan Africa, which is poorly treated with medicines that are toxic, no longer effective or very difficult to administer. New, safe, effective and easy-to-use treatments are urgently needed. Many nitroimidazoles possess antibacterial and antiprotozoal activity and examples such as tinidazole are used to treat trichomoniasis and guardiasis, but concerns about toxicity including genotoxicity limit their usefulness. Fexinidazole, a 2-substituted 5-nitroimidazole rediscovered by the Drugs for Neglected Diseases initiative (DNDi) after extensive compound mining of public and pharmaceutical company databases, has the potential to become a short-course, safe and effective oral treatment, curing both acute and chronic HAT. This paper describes the genotoxicity profile of fexinidazole and its two active metabolites, the sulfoxide and sulfone derivatives. All the three compounds are mutagenic in the Salmonella/Ames test; however, mutagenicity is either attenuated or lost in Ames Salmonella strains that lack one or more nitroreductase(s). It is known that these enzymes can nitroreduce compounds with low redox potentials, whereas their mammalian cell counterparts cannot, under normal conditions. Fexinidazole and its metabolites have low redox potentials and all mammalian cell assays to detect genetic toxicity, conducted for this study either in vitro (micronucleus test in human lymphocytes) or in vivo (ex vivo unscheduled DNA synthesis in rats; bone marrow micronucleus test in mice), were negative. Thus, fexinidazole does not pose a genotoxic hazard to patients and represents a promising drug candidate for HAT. Fexinidazole is expected to enter Phase II clinical trials in 2012.

Safety Study of Culinary-Medicinal Royal Sun Agaricus, Agaricus brasiliensis S. Wasser et al. KA21 (Higher Basidiomycetes) Assessed by Prokaryotic as well as Eukaryotic Systems

As part of the safety evaluation of culinary-medicinal Royal Sun Agaricus, Agaricus brasiliensis KA21, for human consumption, we performed the bacterial reverse mutation test, the mouse micronucleus test, and mouse lymphoma test using A. brasiliensis KA21 as the test substance. The reverse mutation test utilized five bacterial strains, including Salmonella typhimurium TA100, TA1535, TA98, and TA1537, and Escherichia coli WP2 uvrAO. For the micronucleus test we used mice. For the mouse lymphoma test, we used one of the most commonly used mammalian cell mutagenesis systems; the L5178YTK +/- mouse lymphoma-TK assay detects the mutations at the thymidine kinase locus caused by base-pair changes, frameshift, and small deletions. All the tests were conducted according to the guidelines for genotoxicity testing of drugs by the Ministry of Health, Labor, and Welfare, Japan. In the bacterial reverse mutation test, no toxicity was observed up to a dose of 5,000 μg/plate. In the mouse micronucleus test, no toxicity was noted up to a dose of 1 g/kg body weight. In the mouse lymphoma test, frequency of the mutation was equal both in the presence or absence of KA21. Supporting the long history of human consumption of A. brasiliensis, the data shown in this study strongly indicate the safety of this mushroom.

Evaluation of the Genotoxicity of Extracts of Houttuynia cordata Thunb.

The present study was conducted to evaluate the activity of methanol extracts from Houttuynia cordata Thunb. (HC) in a reverse mutation assay in Salmonella typhimurium, and a chromosome aberration assay in the Chinese hamster ovary (CHO) cell line and to evaluate its effect on the occurrence of polychromatic erythrocytes in mice. In the reverse mutation assay using Salmonella typhimurium TA98, TA100, TA1535, and TA1537 and Escherichia coli WP2urvA(-), methanol extracts of HC (5, 2.5, 1.25, 0.62, or 0.312 mg/plate) did not induce reverse mutations in the presence or absence of an S9 metabolic activation mixture. In the chromosome aberration test using CHO cells, methanol extracts (1.25, 2.5 or 5 μg/ml) caused a few incidences of structural and numerical aberrations, in both of absence or presence of an S9 metabolic activation mixture, but in comparison with the positive control group, these incidences were not significantly increased. In the mouse micronucleus test, no significant increases in the occurrence of micronucleated polychromatic erythrocytes were observed in male ICR mice that were orally administered methanol extracts of HC at doses of 2.0, 1.0, or 0.5 g/kg. From these results, we concluded that the methanol extracts of HC did not induce harmful effects on genes in bacteria, a mammalian cell system or in mouse bone marrow cells. Thus, HC's use for health promotion and/or a sick remedy for humans may be safe.

Genotoxicity testing of low molecular weight fucoidan from brown seaweeds

Fucoidan extracts from brown seaweed have anticoagulant, antithrombotic, and antiviral activities. Low molecular weight fucoidan (LMF) obtained by acid hydrolysis of high molecular weight fucoidan showed more favorable bioactivity. Despite extensive work on LMF bioactivities, detailed studies on the genotoxicity of LMF have not been conducted. As part of a safety evaluation, the potential genotoxicity of LMF was evaluated using a standard battery of tests (bacterial reverse mutation assay, chromosomal aberrations assay, and mouse micronucleus assay). The LMF was determined not to be genotoxic under the conditions of the reverse mutation assay, chromosomal aberrations assay, or mouse micronucleus assay. In a reverse mutation assay using four Salmonella typhimurium strains and Escherichia coli, LMF did not increase the number of revertant colonies in any tester strain regardless of metabolic activation by S9 mix, and did not cause chromosomal aberration in short tests with the S9 mix or in the continuous (24h) test. A bone marrow micronucleus test in ICR mice dosed by oral gavage at doses up to 2000mg/kg body weight/day showed no significant or dose-dependent increases in the frequency of micronucleated polychromatic erythrocytes. Use of LMF is presently expected to be safe, as anticipated intake is small compared to doses administered in the genotoxicity assays and may prove to be a useful bioactive agent after further toxicity research.

In vitro and in vivo assessment of the mutagenic activity of N-[ N-[3-(3-hydroxy-4-methoxyphenyl) propyl]-α-aspartyl]- l-phenylalanine 1-methyl ester, monohydrate (advantame)

Advantame (N-[ N-[3-(3-hydroxy-4-methoxyphenyl) propyl]-α-aspartyl]- l-phenylalanine 1-methyl ester, monohydrate), an N-substituted analogue of aspartame, has been developed as a high-intensity sweetener. It is approximately 100 and 20,000 times sweeter than aspartame and sucrose, respectively. In this study the safety of advantame has been evaluated using a series of in vitro and in vivo genotoxicity assays including, bacterial mutation, mammalian cell mutation, and mouse micronucleus tests. Advantame did not induce reverse mutations in Salmonella typhimurium and Escherichia coli at concentrations of up to 5000 μg/plate. In the mammalian cell mutation assay, advantame did not induce mutation at the Hprt locus of L5178Y mouse lymphoma cells in two independent experiments, either in the absence or presence of S9. In vivo, there was no effect on the incidence of micronucleated immature or mature erythrocytes in bone marrow after oral administration of the test substance at any dose level (up to 2000 mg/kg body weight) or sampling time (24 and 48 h). The results of these studies demonstrate that advantame is without genotoxic potential.

Genotoxicity assessment of ethylenediamine dinitrate (EDDN) and diethylenetriamine trinitrate (DETN)

Ethylenediamine dinitrate (EDDN) and diethylenetriamine trinitrate (DETN) are relatively insensitive explosive compounds that are being explored as safe alternatives to other more sensitive compounds. When used in combination with other high explosives they are an improvement and may provide additional safety during storage and use. The genetic toxicity of these compounds was evaluated to predict the potential adverse human health effects from exposure by using a standard genetic toxicity test battery which included: a gene mutation test in bacteria (Ames), an in vitro Chinese Hamster Ovary (CHO) cell chromosome aberration test and an in vivo mouse micronucleus test. The results of the Ames test showed that EDDN increased the mean number of revertants per plate with strain TA100, without activation, at 5000μg/plate compared to the solvent control, which indicated a positive result. No positive results were observed with the other tester strains with or without activation in Salmonella typhimurium strains TA98, TA1535, TA1537, and Escherichia coli strain WP2 uvrA. DETN was negative for all Salmonella tester strains and E. coli up to 5000μg/plate both with and without metabolic activation. The CHO cell chromosome aberration assay was performed using EDDN and DETN at concentrations up to 5000μg/mL. The results indicate that these compounds did not induce structural chromosomal aberrations at all tested concentrations in CHO cells, with or without metabolic activation. EDDN and DETN, when tested in vivo in the CD-1 mouse at doses up to 2000mg/kg, did not induce any significant increase in the number of micronuclei in bone marrow erythrocytes. These studies demonstrate that EDDN is mutagenic in one strain of Salmonella (TA100) but was negative in other strains, for in vitro induction of chromosomal aberrations in CHO cells, and for micronuclei in the in vivo mouse micronucleus assay. DETN was not genotoxic in all in vitro and in vivo tests. These results show the in vitro and in vivo genotoxicity potential of these chemicals.

Genotoxicity potential of a new natural formicide

Assessment of environmental impacts from pesticide utilization should include genotoxicity studies, where the possible effects of mutagenic/genotoxic substances on individuals are assessed. In this study, the genotoxicity profile of the new formicide Macex® was evaluated with two genotoxicity tests, namely, the micronucleus test with mouse bone marrow and Vicia faba, and a mutagenicity test using the Ames Salmonella assay. The bacterial reverse mutation test (Salmonella typhimurium strains TA97, TA98, TA100, TA102, and TA1535), the Vicia root tip and mouse micronucleus tests were conducted according to published protocols. In the range of the formicide Macex® concentrations tested from 0.06 to 1.0 g L⁻¹ (or mgkg⁻¹ in the mouse test), no genotoxicity was observed in the prokaryotic or eukaryotic test organisms. However, at Macex® concentrations of 0.5 g L⁻¹ and above a significant decrease in the mitotic index (P ≤ 0.05) in the V. faba was observed. Micronucleus formation was likewise increased in the test organism at concentrations starting at 2.0 g L⁻¹. These data allow us to classify this natural formicide preparation as a product with no geno-environmental-impact when applied at recommended concentrations.

In vitro and in vivo assessment of the genotoxic activity of aloesin

Aloesin is a chromone that is a component of Aloe spp. It may have potential as a functional food ingredient as it has been shown to likely have beneficial effects in persons in a pre-diabetic state or who have metabolic syndrome. In this study the safety of aloesin has been evaluated using a series of in vitro and in vivo genotoxicity assays including, bacterial mutation, mammalian cell cytogenetic, and mouse micronucleus tests. Aloesin did not induce reverse mutations in Salmonella typhimurium and Escherichia coli at any of the tested dose levels up to 10,000μg/plate. Similarly, aloesin did not increase the incidence of chromosome aberrations when incubated with Chinese hamster lung cells at any of the tested concentrations up to 10,000μg/mL. In vivo, there was no effect of aloesin on the incidence of micronucleated erythrocytes following oral administration on two consecutive days at doses up to 5000mg/kg body weight. There was no evidence of toxicity to bone marrow. The results of these studies demonstrate that aloesin is without genotoxic potential.

Safety evaluation of steroidal saponin DT-13 isolated from the tuber of Liriope muscari (Decne.) Baily

Steroidal saponin DT-13 (25 (R, S)-ruscogenin-1-O-[β-d-glucopyranosyl - (1→2)] [β-d-xylopyranosyl-(1→3)]-β-d-fucopyranoside) is the main active component of the tube of Liriope muscari (Decne.) Baily and has been studied as a candidate drug for cancer metastasis. The objective of this study was to evaluate the safety of DT-13 systematically by genotoxicity and acute oral toxicity and subchronic 90-day oral gavage toxicity. Results of Ames test confirmed that DT-13 did not induce mutations in histidine auxotrophs Salmonella typhimurium (TA 97, TA 98, TA 100 and TA 102) both in the presence and absence of metabolic activation system at the doses of 0.05–500μg/plate. Meanwhile, DT-13 did not induce clastogenicity at doses of 1250, 2500 and 5000mg/kg in mouse micronucleus test. And the single oral dose of DT-13 at 5000mg/kg did not produce mortality or significant changes in the general behavior and gross appearance of the internal organs of mice. In subchronic toxicity study, DT-13 was administrated to Sprague–Dawley rats via oral gavage at doses of 10, 60 and 360mg/kg for 90days. Necropsy, hematological and biochemical analysis, and histopathological examination did not reveal any remarkable and treatment related changes. In conclusion, DT-13 is of low toxicity at the tested doses.

Micronucleus Test of Picrorrhiza Rhizoma Aqueous Extract in Bone Marrow Cells of Male ICR Mice.

In this research, the genotoxic effect of Picrorrhiza Rhizoma (PR) aqueous extract was evaluated using the mouse micronucleus test. PR extract was administered once a day for 2 continuous days by oral gavage to male ICR mice at doses of 2000, 1000 and 500 mg/kg. Cyclophosphamide was used as a known genotoxic agent in a positive control. The appearance of a micronucleus (MN) in polychromatic erythrocyte (PCE) is used as an index for genotoxic potential, and PCE ratio is used as an index of cytotoxicity. Although significant (p < 0.01) increase of the number of PCE with one or more nuclei (MNPCE) was detected in cyclophosphamide treated groups, no significant increases of MNPCE numbers were observed in all three different dosages of PR extracts treated mice with over 0.39 of the individual polychromatic erythrocyte ratio in all mice used in this study. The results obtained indicated that PR extract shows no genotoxicity effects up to 2000 mg/kg dosing levels.

Melamine induces sperm DNA damage and abnormality, but not genetic toxicity

Melamine is a category III carcinogen. However, its illegal addition to milk and other protein products has led to the pet melamine poisoning in USA and infant renal calculus cases in China. Its long-term toxicity is not clear and needs to be investigated urgently to appease the public panic. In this study, the effects of melamine on mutagenesis in prokaryotes and eukaryotes were tested by Ames test, in vitro mammalian chromosome aberration test, mouse micronucleus test and sperm abnormality test; the effects of melamine on DNA damage in sperm cells were observed by single cell gel electrophoresis, and the effects on malignant transformation were examined by malignant transformation experiment of normal human liver cell line L02. The results show that melamine has no mutagenic function in prokaryotes and eukaryotes in vitro and in vivo, and does not induce malignant cell transformation after long-term exposure. However, it has ability to increase sperm abnormality rate and DNA damage.

Assessment of the mutagenic and antimutagenic activity of Synadenium umbellatum Pax latex by micronucleus test in mice

Synadenium umbellatum Pax, popularly known as "cola-nota", is a medicinal plant that grows in tropical regions. The latex of this plant is used against various diseases, such as diabetes mellitus, leprosy, tripanosomiasis, leukemia, and several malignant tumors. The mutagenic, antimutagenic, and cytotoxic effects of the latex of this plant were investigated by measuring the frequency of micronuclei in mice bone marrow cells. To evaluate mutagenicity, the animals were treated with four doses of latex (10, 30, 50, and 100 mg/kg body weight). To study the antimutagenic activity, the animals were simultaneously treated with latex and mitomycin C (4 mg/kg). The cytotoxicity was evaluated by polychromatic and normochromatic erythrocytes ratio. Our results showed a significant increase of frequency of micronucleated polychromatic erythrocytes (MNPCE) compared to the negative control group (p < 0.05). Concerning antimutagenicity, the doses of 10 and 30 mg/kg co-administered with mitomycin C showed significant decrease in MNPCE frequency compared to the positive control group (p < 0.05). However, no significant reduction in MNPCE frequency (p > 0.05) was detected at the doses of 50 and 100 mg/kg. Under our experimental conditions, the results obtained indicate strong mutagenic and cytotoxic activity of S. umbellatum latex except the dose of 10 mg/kg and moderate antimutagenic effect at lower doses.

Bacterial Reverse Mutation Test and Micronucleus Test of Fucoxanthin Oil from Microalgae

Fucoxanthin-containing oil extracted from microalga, Chaetoseros sp., was subjected to genotoxicity studies, the bacterial reverse mutation test and the micronucleus test in mice. The number of revertant colonies in fucoxanthin oil-treated plates of all strains tested was less than twice the number of colonies in the negative control, regardless of the presence of the metabolic activator in the bacterial reverse mutation test. In the micronucleus test, 500, 1,000, 2,000 mg/kg body weight of fucoxanthin oil was administered orally to mice. There was no significant increase in micronucleus frequency in bone marrow cells. These results suggest that fucoxanthin oil does not exhibit genotoxicity.

Zanthoxylum chiloperone leaves extract: First sustainable Chagas disease treatment

Zanthoxylum chiloperone var. angustifolium Engl. (Rutaceae) stem bark is used traditionally in Paraguay for its antiparasitic properties. Canthin-6-one is main compound isolated from Zanthoxylum chiloperone var angustifolium with broad spectrum antifungal, leishmanicidal and trypanocidal activities. The qualitative and quantitative characterization and the isolation of main alkaloidal components of different organs of Zanthoxylum chiloperone are investigated by HPLC-UV-MS. The in vitro biological activity of each extract against trypomastigote and amastigote forms of Trypanosoma cruzi parasites were evaluated, then comparison the in vivo efficacy of the ethanolic leaves extract of Zanthoxylum chiloperone with reference drug, benznidazole, in acute Trypanosoma cruzi infected mice when administered by oral route. We have also evaluated the mutagenic and cytotoxic activity of the main component of Zanthoxylum chiloperone, i.e. canthin-6-one, by mouse bone marrow micronucleus test. The compositions of the ethanol extracts obtained after the maceration process were studied by HPLC-UV-MS methods. The quantitation analysis was performed by external standard method, using a calibration curve constructed utilizing solutions containing different concentrations of the reference samples. The anti-trypomastigote activity was evaluated by the lysis effect on mouse blood trypomastigotes (Y strain Trypanosoma cruzi). The anti-amastigote Trypanosoma cruzi activity was evaluated by a modified colorimetric method with chlorophenol red-β-d-galactopyranoside (CPRG). The cytotoxicity of extracts and compounds was performed on NCTC 929 cells. The in vivo efficacy of the ethanolic leaves extract of Zanthoxylum chiloperone and benznidazole, in acute Trypanosoma cruzi (two different strains) was evaluated in Trypanosoma cruzi infected mice; the drugs were administered by oral route. The mortality rates were recorded and parasitaemias in control and treated mice were determined once weekly for 70 days. The mutagenic and cytotoxic activity of the main component of Zanthoxylum chiloperone, canthin-6-one, by mouse bone marrow micronucleus test. Canthin-6-one was the main compound of stem and root bark and 5-methoxy-canthin-6-one in leaves and fruits. The ethanolic leaves extract, canthin-6-one and benznidazole presented, approximately, the same level of in vitro activity against trypomastigote and amastigote forms of Trypanosoma cruzi. We have also evaluated the mutagenic and cytotoxic effects of canthin-6-one by micronucleus test in mice. This test showed any mutagenic and cytotoxic damages. The effects of oral or subcutaneous treatments at 10 mg/kg daily for 2 weeks with the ethanolic extract of leaves of Zanthoxylum chiloperone were examined in Balb/c mice infected acutely with Trypanosoma cruzi (CL or Y strain) and compared with benznidazole at 50 mg/kg for 2 weeks. In these experiments, 70 days after infection, parasitaemia and serological response were significantly reduced with the oral ethanolic extract treatment compared with reference drug. This study have shown the efficacy of the leaves extract of Zanthoxylum chiloperone in reducing Trypanosoma cruzi parasitaemia in vivo assays and could be welcomed by scientific and rural communities of Paraguay because it could help them towards the use of local resources to treat an endemic infection, Chagas disease, affecting 20% of the population of this country.

Assessment of the Genotoxic, Antigenotoxic, and Cytotoxic Activities of the Ethanolic Fruit Extract of Solanum lycocarpum A. St. Hill. (Solanaceae) by Micronucleus Test in Mice

Solanum lycocarpum A. St. Hill. (Family Solanaceae), popularly known in Brazil as lobeira, is a common weed in the Brazilian Cerrado vegetation. The fruits of this species have been used in Brazil for culinary purposes and in folk medicine as a sedative, diuretic, antiepileptic, antispasmodic, hypoglycemic, and hypocholesterolemic agent as well as in the control of obesity. Due to the spreading use of this plant as a therapeutic resource and food, the present study aimed to evaluate the genotoxic, antigenotoxic, and cytotoxic effects of S. lycocarpum ethanolic fruit extract using the mouse bone marrow micronucleus test. Both genotoxicity and antigenotoxicity of this ethanolic fruit extract were evaluated by using the frequency of micronucleated polychromatic erythrocytes, whereas cytotoxicity was assessed by the polychromatic and normochromatic erythrocytes ratio. Our results indicated that although S. lycocarpum ethanolic fruit extract did not exhibit genotoxic effect in mice bone marrow, both cytotoxic and antigenotoxic actions were evidenced at all tested doses.

Antioxidant and antimutagenic activities of bark extract of Terminalia arjuna

Objective The alcoholic extract of stem bark of Terminalia arjuna (ALTA) was screened for antioxidant and antimutagenic (anticlastogenic) activity. Methods Antioxidant property was determined by 1, 1, Diphyny l, 2-Picryl hydrazyl (DPPH) assay, super oxide radical scavenging activity, lipid peroxidation assay and total polyphenolic content was determined by Folin-Ciocalteau's reagent. Antimutagenic activity was evaluated using micronucleus test in mice. Results The ALTA has shown potent antioxidant activity with EC 50 of 2.491±0.160, 50.110±0.150 & 71.000±0.250 in DPPH assay, superoxide radical scavenging activity and lipid peroxidation assay, which is comparable with ascorbic acid with EC 50 of 2.471±0.140, 40.500±0.390 and 63.000±0.360 respectively. In micronucleus test, ALTA (100 & 200mg/kg, p.o.) showed significant reduction in percentage of micronucleus in both polychromatic erythrocytes (PCE) and normochromatic erythrocytes (NCE) and also shown significant reduction in P/N ratio. Conclusions These results suggested that ALTA possess significant antioxidant and antimutagenic activity.

Solanum paniculatum L. Leaf and Fruit Extracts: Assessment of Modulation of Cytotoxicity and Genotoxicity by Micronucleus Test in Mice

Solanum paniculatum L. is a plant species widespread throughout tropical America, especially in the Brazilian Savanna region. It is used in Brazil for culinary purposes and in folk medicine to treat liver and gastric dysfunctions, as well as hangovers. Previous studies with S. paniculatum ethanolic leaf extract (ELE) or ethanolic fruit extract (EFE) demonstrated that they have no genotoxic activity meant either in the micronucleus test in mice or in the phage induction SOS Inductest in bacterial strains; however, cytotoxicity was demonstrated in both tests. Because of the spread use of this plant as a therapeutic resource and food, the present study aimed at evaluating the modulator effects of S. paniculatum ELE or EFE against mitomycin C (MMC) using the mouse bone marrow micronucleus test. This short-term test was used to detect the acute effects of responsive erythropoiesis after 24- and 48-hour exposure periods. Swiss-Webster mice were orally treated with three different concentrations (100, 200, or 300 mg/kg) of ELE or EFE simultaneously with a single dose of MMC (4 mg/kg i.p.). Antigenotoxicity was evaluated using the frequency of micronucleated polychromatic erythrocytes (MNPCEs), whereas anticytotoxicity was assessed by the polychromatic/normochromatic erythrocyte ratio. Our results demonstrated that neither the ELE nor EFE of S. paniculatum protected cells against the cytotoxic action of MMC. Nevertheless, the present study showed the antimutagenic effect of ELE after a 24-hour treatment (reduction in the frequencies of MNPCEs after a 48-hour treatment with ELE can be due to toxicity) and no antimutagenic action of the EFE treatment against the aneugenic and/or clastogenic activities of MMC.