Genotoxic and cytotoxic evaluation of venlafaxine in an acute and a subchronic assay in mouse

Abstract The present research was made to determine the micronuclei and cytotoxic capacity of the antidepressant venlafaxine in an in vivo acute and subchronic assays in mouse. In the first study, we administered once 5, 50, and 250 mg/kg of the drug, and included a negative and a daunorubicin treated group. Observations were daily made during four days. The subchronic assay lasted 5 weeks with daily administration of venlafaxine (1, 5, and 10 mg/kg) plus a negative and an imipramine administered groups. Observations were made each week. In the first assay results showed no micronucleated polychromatic erythrocytes (MNPE) increase, except with the high dose at 72 h. The strongest cytotoxic effect was found with 250 mg/kg at 72 h (a 51% cytotoxic effect in comparison with the mean control level). In the subchronic assay no MNPE increase was found; however, with the highest dose a significant increase of micronucleated normochromatic erythrocytes was observed in the last three weeks (a mean of 51% respect to the mean control value). A cytotoxic effect with the two high doses in the last two weeks was observed (a polychromatic erythrocyte mean decrease of 52% respect to the mean control value). Results suggest caution with venlafaxine.

Resumo A presente pesquisa foi feita para determinar a capacidade micronuclei e citotóxica do antidepressivo venlafaxina em ensaios agudos e subcrônicos in vivo em camundongos. No primeiro estudo, administramos uma vez 5, 50 e 250 mg/kg do medicamento e incluímos um grupo negativo e um grupo tratado com daunorubicina. As observações foram feitas diariamente durante quatro dias. O ensaio subcrônico durou cinco semanas com administração diária de venlafaxina (1, 5, e 10 mg/kg) mais um grupo negativo e um grupo administrado de imipramina. As observações foram feitas a cada semana. No primeiro ensaio, os resultados não mostraram aumento de eritrócitos policromáticos micronucleados (MNPE), exceto com a dose elevada a 72 h. O efeito citotóxico mais forte foi encontrado com 250 mg/kg a 72 h (um efeito citotóxico de 51% em comparação com o nível médio de controle). No ensaio subcrônico não foi encontrado aumento de MNPE; entretanto, com a dose mais alta, um aumento significativo de eritrócitos normocromáticos micronucleados foi observado nas últimas três semanas (média de 51% em relação ao valor médio de controle). Foi observado um efeito citotóxico com as duas altas doses nas últimas duas semanas (uma diminuição média de 52% em relação ao valor médio de controle dos eritrócitos policromáticos). Os resultados sugerem cautela com a venlafaxina.

Genotoxic and cytotoxic evaluation of venlafaxine in an acute and a subchronic assay in mouse / Avaliação genotóxica e citotóxica da venlafaxina em ensaio agudo e subcrônico em camundongos

Abstract The present research was made to determine the micronuclei and cytotoxic capacity of the antidepressant venlafaxine in an in vivo acute and subchronic assays in mouse. In the first study, we administered once 5, 50, and 250 mg/kg of the drug, and included a negative and a daunorubicin treated group. Observations were daily made during four days. The subchronic assay lasted 5 weeks with daily administration of venlafaxine (1, 5, and 10 mg/kg) plus a negative and an imipramine administered groups. Observations were made each week. In the first assay results showed no micronucleated polychromatic erythrocytes (MNPE) increase, except with the high dose at 72 h. The strongest cytotoxic effect was found with 250 mg/kg at 72 h (a 51% cytotoxic effect in comparison with the mean control level). In the subchronic assay no MNPE increase was found; however, with the highest dose a significant increase of micronucleated normochromatic erythrocytes was observed in the last three weeks (a mean of 51% respect to the mean control value). A cytotoxic effect with the two high doses in the last two weeks was observed (a polychromatic erythrocyte mean decrease of 52% respect to the mean control value). Results suggest caution with venlafaxine.

Resumo A presente pesquisa foi feita para determinar a capacidade micronuclei e citotóxica do antidepressivo venlafaxina em ensaios agudos e subcrônicos in vivo em camundongos. No primeiro estudo, administramos uma vez 5, 50 e 250 mg/kg do medicamento e incluímos um grupo negativo e um grupo tratado com daunorubicina. As observações foram feitas diariamente durante quatro dias. O ensaio subcrônico durou cinco semanas com administração diária de venlafaxina (1, 5, e 10 mg/kg) mais um grupo negativo e um grupo administrado de imipramina. As observações foram feitas a cada semana. No primeiro ensaio, os resultados não mostraram aumento de eritrócitos policromáticos micronucleados (MNPE), exceto com a dose elevada a 72 h. O efeito citotóxico mais forte foi encontrado com 250 mg/kg a 72 h (um efeito citotóxico de 51% em comparação com o nível médio de controle). No ensaio subcrônico não foi encontrado aumento de MNPE; entretanto, com a dose mais alta, um aumento significativo de eritrócitos normocromáticos micronucleados foi observado nas últimas três semanas (média de 51% em relação ao valor médio de controle). Foi observado um efeito citotóxico com as duas altas doses nas últimas duas semanas (uma diminuição média de 52% em relação ao valor médio de controle dos eritrócitos policromáticos). Os resultados sugerem cautela com a venlafaxina.

Genotoxic and cytotoxic evaluation of venlafaxine in an acute and a subchronic assay in mouse.

The present research was made to determine the micronuclei and cytotoxic capacity of the antidepressant venlafaxine in an in vivo acute and subchronic assays in mouse. In the first study, we administered once 5, 50, and 250 mg/kg of the drug, and included a negative and a daunorubicin treated group. Observations were daily made during four days. The subchronic assay lasted 5 weeks with daily administration of venlafaxine (1, 5, and 10 mg/kg) plus a negative and an imipramine administered groups. Observations were made each week. In the first assay results showed no micronucleated polychromatic erythrocytes (MNPE) increase, except with the high dose at 72 h. The strongest cytotoxic effect was found with 250 mg/kg at 72 h (a 51% cytotoxic effect in comparison with the mean control level). In the subchronic assay no MNPE increase was found; however, with the highest dose a significant increase of micronucleated normochromatic erythrocytes was observed in the last three weeks (a mean of 51% respect to the mean control value). A cytotoxic effect with the two high doses in the last two weeks was observed (a polychromatic erythrocyte mean decrease of 52% respect to the mean control value). Results suggest caution with venlafaxine.

Evaluation of teratogenicity and genotoxicity induced by kramecyne (KACY).

Kramecyne (KACY), a polymer isolated from Krameria cytisoides Cav, has anti-inflammatory, anti-nociceptive, anti-arthritic and anti-ulcerogenic properties. As a part of standard preclinical safety tests, the present study sought to determine potential developmental toxicity (in female rats) and genotoxicity (in male mice) of KACY. Pregnant female rats were divided into six groups: the negative control (vehicle), the positive control (250 mg/kg of acetylsalicylic acid (ASA)), and four experimental groups (50, 250, 500 and 1000 mg/kg of KACY). To evaluate genotoxicity by in vivo micronuclei (MN) and sister chromatid exchange (SCE) tests, male mice were divided into five groups: the negative control (vehicle), the positive control (1.5 and 2.5 mg/kg of doxorubicin for MN and SCE, respectively), and three experimental groups (50, 500 and 1000 mg/kg of KACY). All treatments were administered by oral gavage. A slight maternal toxicity was evidenced by lower weight gain for rats receiving 500 and 1000 mg/kg of KACY, but no fetal malformations were found. However, there were less live fetuses/litter and greater post-implantation loss/litter at these two doses. Manifestations of developmental toxicity were limited to a higher rate of skeletal alterations. The MN tests did not evidence genotoxicity or cytotoxicity. KACY caused a slightly but significantly increased frequency of SCE. Although KACY-treated rats had skeletal alterations, these apparently were not caused by a mechanism of genotoxicity. Furthermore, the same administration in adult male mice did not produce genotoxicity. Hence, KACY herein proved to be safe for rats during the period of organogenesis.

Inhibitory effect of grapefruit juice on the genotoxicity induced by hydrogen peroxide in human lymphocytes.

By means of the comet assay we demonstrated a strong effect by hydrogen peroxide (HP) and no damage by grapefruit juice (GJ) in human lymphocytes. Cells exposed to HP and treated with three concentrations of GJ (10-90 min) showed an increase of DNA damage by HP over the control level, and a decrease of such damage by GJ. With the comet assay plus formamidopyrimidine-DNA-glycosylase we found the strongest increase of DNA damage by HP over the control level, and the strongest reduction of such damage by GJ. By applying the comet/FISH method we determined 98% of the p53 gene signals in the comet head of control cells along the experiment (10-90 min), in contrast with about 90% signals in the comet tail of cells exposed to HP. Cells treated with both agents showed a significant, concentration/time dependent return of p53 signals to the head, suggesting enhancement of the gene repair. Finally, with the annexin V assay we found an increase in apoptosis and necrosis by HP, and no effect by GJ; when GJ was added to HP treated cells no modification was observed in regard to apoptosis, although a decrease of necrosis was observed.

The antigenotoxic effects of grapefruit juice on the damage induced by benzo(a)pyrene and evaluation of its interaction with hepatic and intestinal Cytochrome P450 (Cyp) 1a1.

We determined the capacity of grapefruit juice (GJ) to inhibit the rate of micronucleated polychromatic erythrocytes (MNPE) in mice treated with benzo(a)pyrene (BaP), an environmental contaminant that is biotransformed by Cyp1a1 and is a strong genotoxic agent. For this study, we administered 4.1, 20.8, and 41.6 µl/g body weight (b.w.) of GJ to BaP-treated mice (340 mg/kg). We found a significant decrease in the frequency of MNPE at 48 and 72 h compared to BaP-only treated animals. In turn, no prevention of the cytotoxic damage induced by BaP was found. We next explored whether GJ's antigenotoxic mechanism of action was related to an inhibitory effect on the activity of the Cyp1a1 enzyme. A reduction in microsomal hepatic and intestinal ethoxyresorufin-O-deethylase (EROD) activity of 20% and 44%, respectively, was found in mice treated with BaP and GJ compared to BaP-only treated animals. Furthermore, when EROD inhibition was tested in vitro, we found a concentration-dependent EROD inhibition by GJ, which reached 85% of the maximum level. Together, these results suggest that the protective effect of GJ against the genotoxicity of BaP may be related to the inhibition of Cyp1a1 enzyme activity.

Chromosomal aberrations induced by imipramine and desipramine in mouse.

Imipramine (IMI) and desipramine (DES) are two drugs widely used for the treatment of depression as well as for other diseases. In the present study, we determined their capacity to induce chromosomal aberrations in mouse bone marrow cells. Three doses of each compound were tested and their results were compared with the frequency of chromosomal aberrations obtained in a control group as well as with a group treated with cyclophosphamide. Our results showed a significant increase in chromosome damage with the doses tested for each compound: 7, 20, and 60 mg/kg in the case of IMI, and 2, 20, and 60 mg/kg as regards DES. This last drug induced stronger chromosomal damage than IMI. Our results agree with previous studies regarding the induction of micronuclei and sister chromatid exchanges by the drugs in mouse and suggest caution with respect to their use in long-term treatments.

Glycine decreases developmental damage induced by hyperglycaemia in mouse embryos.

Hyperglycaemia induces neural tube defects and growth retardation in cultured mouse and rat embryos. In this study the possibility that glycine could prevent hyperglycaemia-induced embryopathy was researched. Early somite mouse embryos were cultured in normal medium, hyperglycaemic medium (50 mmol L(-1) glucose), or with glycine (1 mmol L(-1)) supplementation of normal and hyperglycaemic rat serum for 48 h. The embryo growth and differentiation were determined to estimate developmental and congenital malformations as well as lipid peroxidation levels. Adding glycine to the control culture medium did not affect embryonic development. Whereas the amino acid protected against telencephalon dysmorphogenesis, the decreased DNA content and number of somites, and the morphological score affectation induced by the hyperglycaemic medium, it had no preventive effect on the retarded differentiation of the otic system. Moreover, it prevented the high hyperglycaemia-induced lipoperoxidation levels of embryonic tissues. Embryos were partially protected from the hyperglycaemia-induced teratogenesis due to the antioxidative effect of glycine. As no other mechanisms related to the antiglycation or other protective effects of glycine were examined, the mechanism whereby it acted as an antiteratogenic agent needs further study.

Cell protection induced by beta-sitosterol: inhibition of genotoxic damage, stimulation of lymphocyte production, and determination of its antioxidant capacity.

Beta-sitosterol (BS) is a compound that has shown various activities potentially useful for human health. In the present study, we determined its antigenotoxic capacity and lymphocyte induction potential in mouse as well as its capacity to trap free radicals in vitro. BS, in doses from 200 to 1,000 mg/kg, was able to significantly reduce the frequency of sister chromatid exchanges induced by 10 mg/kg of doxorubicin (DX) in bone marrow cells. The same range of BS doses also gave rise to a strong reduction in the rate of micronucleated, polychromatic erythrocytes induced by DX. In addition, we determined an increase in the production of lymphocytes in mice administered with BS. By means of the DPPH assay, the compound was shown to trap free radicals in a concentration dependent manner as high as 78.12% using 250 mug/ml. Our research established three relevant biological activities of BS which show its potential as a chemopreventive agent.

Chemoprotective effect of Spirulina (Arthrospira) against cyclophosphamide-induced mutagenicity in mice.

The aim of this study was to investigate the antimutagenic effects of Spirulina (SP) on male and female mice by the dominant lethal test using cyclophosphamide (CP) as a mutagen. Animals of both sex were given SP orally at 0, 200, 400 or 800 mg/kg body weight (b.w.) for 2 weeks prior to starting the CP treatment. CP was i.p. injected daily for 5 days at 40 mg/kg b.w. For the male-dominant lethal test, each male was caged with untreated females per week for 3 weeks. For the female-dominant lethal test the above doses and schedule treatments were used and treated females were caged for one week with untreated males (1-2). On days 13-15 after breeding was |started all the females were evaluated for incidence of pregnancy, total corpora lutea, total implants and pre- and post-implant losses. In the male-dominant lethal test, the CP induced pre- and post-implant losses in untreated females were inhibited at all SP doses. In the female-dominant lethal test only post-implantation losses were prevented at the same doses. Semen examination of a separate group of mice showed that SP improved its quality. Our results illustrate protective effects of SP in relation to CP-induced genetic damage to germ cells.

Genotoxic and oxidative damage induced by Helicobacter pylori in Meriones unguiculatus.

Infection with Helicobacter pylori has been shown to be at the origin of various gastric pathologies. However, it has not yet been established whether the etiology of such diseases, particularly of gastric cancer, is related to the production of free radicals or to mutagenesis. The aim of this study was to determine whether a six-month infection with Helicobacter pylori increased the amount of lipid peroxidation, nitric oxide, and DNA damage in Mongolian gerbils (Meriones unguiculatus). H. pylori was characterized genotypically and administered orally to the animals. Four tests were applied to identify the presence of bacteria at one, two, four, and six months after the inoculation, namely, isolation and identification in culture, the urease test, the ELISA assay, and immunohistochemical staining of gastric biopsies. The infection was considered to be successful when three of the above-mentioned tests were positive. The infection occurred in 30% of the animals in the first month after the H. pylori inoculation and in 60-70% of the animals in the later stages. Levels of malondialdehyde, nitric oxide, and DNA damage (using the "comet" assay) were determined in the gastric tissue of the animals at one, two, four, and six months. We found statistically significant increases in malondialdehyde and nitric oxide levels from the second month on. The comet assay in animals infected with H. pylori showed a significant increase in the mean tail length throughout the observation period. We conclude that our results support the assumption that oxidative damage and DNA breakage produced by the infection with H. pylori are some of the initial alterations occurring in the development of gastric diseases.

Inhibitory effect of mannan on the toxicity produced in mice fed aflatoxin B1 contaminated corn.

Aflatoxin B(1) (AFB(1)) is a potent mutagenic and carcinogenic agent found in numerous agricultural and dairy products consumed by humans. Therefore, we evaluated the capacity of mannan to cope with its genotoxic potential. We prepared a diet constituted of corn (90%) plus the recommended amount of other nutrients, as well as with the tested compounds (mannan and/or AFB(1)). Mice were fed this diet during 4 weeks as follows: one group with AFB(1)-contaminated corn (0.25 mg/kg of corn), three groups with mannan (50, 250, and 500 mg/kg of corn) plus AFB(1) (0.25 mg/kg), another group with only mannan (500 mg/kg), and the last group with an uncontaminated diet and no mannan added. We determined the weight, the micronucleated normochromatic erythrocyte rate (MNNE), the polychromatic/normochromatic index, and the sister chromatid exchange rate (SCE). We also examined the recovery response of mice during 4 additional weeks, when they were fed only the normal diet without AFB(1) or mannan. The results in the first period revealed the following: a) mice fed with mannan alone presented values in the range determined for the control group; b) mice fed AFB(1) had a significant weight decrease, as well as a significant increase in the rate of MNNE and SCE; and c) animals fed the combined regimen (AFB(1) plus mannan) presented a 25% weight increase with respect to the animals treated with AFB(1) alone, as well as a significant reduction in the level of MNNE and SCE with the two high doses tested. In the second (recovery) period, the control and the mannan fed groups maintained values similar to those exhibited in the previous phase, and the AFB(1) group as well as the groups fed the regimen combined with mannan showed an improvement in all evaluated parameters; the best response was that found in mice fed AFB(1) plus 500 mg/kg of mannan. Our study established an antigenotoxic effect of mannan that could be due to its adsorbent capacity.

Antimutagenicity of Stevia pilosa and Stevia eupatoria evaluated with the Ames test.

Stevia pilosa and Stevia eupatoria are plants used for various purposes in traditional medicine. In this report we studied the antimutagenic effect of methanolic extracts obtained from leaves, root, and flowers of the two species using the Ames test with and without metabolic activation. We tested the effect of the extracts on the damage induced by three mutagens with the following results: 1 - we found an inhibitory effect of both species on the mutagenicity induced by 2-aminoanthracene in the strain TA98. The best antimutagenic effect was obtained with leaves of both species and the flowers of S. eupatoria (99%), 2 - the mutations induced with N-ethyl-N'-nitro-N-nitrosoguanidine in the strain TA100 was also reduced. The flowers of S. pilosa and the root of S. eupatoria showed about 93% of inhibition, 3 - finally, the mutations induced by mitomycin-C on the strain TA102 had a reduction of 87% with the leaves of S. eupatoria. Besides, we determined the radical scavenging potential of the extracts with the DPPH method, and found a potent effect produced by all extracts, with an efficacy of more than 90%. The present study showed both antimutagenic and antioxidant potential of the tested extracts, and suggest the pertinence to confirm these effects in other models, and to accurately determine their mechanism of action.

Antigenotoxic effect of Saccharomyces cerevisiae on the damage produced in mice fed with aflatoxin B(1) contaminated corn.

The potential of Saccharomyces cerevisiae (Sc) was evaluated for reducing the micronucleated normochromatic erythrocytes (MNNE) rate in mice fed AFB(1) contaminated corn. The study included two groups fed AFB(1) contaminated corn (0.4 and 0.8 mg/kg), a control fed uncontaminated corn, another group fed uncontaminated corn and 0.3% of Sc (1 x 10(8) live cells/g), and two groups fed AFB(1) contaminated corn (0.4 and 0.8 mg/kg) plus 0.3% Sc. Weight and MNNE were determined weekly for six weeks. Subsequently, the same determinations were made for another three-week period, but in mice receiving only a normal diet, without AFB(1) and Sc. Results in the first period revealed the following: control and Sc fed mice had similar constant weight increase, and low MNNE rate; mice fed only AFB(1) showed weight decrease and significant MNNE increase; finally, Sc improved weight gain and reduced MNNE produced by AFB(1). In the second period, results exhibited a tendency similar to that of the previous phase in the control and Sc fed mice; the weight and MNNE values improved in the other groups. We also determined the capacity of Sc for adsorbing and modifying the mycotoxin structure. The mixture was filtered to obtain two phases, and AFB(1) content was measured. Sc revealed a potent adsorbent capacity; however, chromatographic determination suggested no structural modification.

Determination of DNA damage in floriculturists exposed to mixtures of pesticides.

The aim of the study was to determine possible DNA damage in floriculturists chronically exposed to pesticides. Leukocytes from 52 workers, 46 environmentally exposed, and 38 control individuals were evaluated with the comet assay. Serum from all individuals was also analyzed for pesticides using gas chromatography coupled to mass spectrometry. A statistically significant difference in DNA fragmentation in the pesticide exposed group compared to the other two groups (P < .001) was found. No differences between environmentally exposed and control individuals were detected. The statistical analysis showed no significant correlation between DNA damage and sex, age, drinking or smoking habits, as well as years of exposure. One or more pesticides were detected in 50% of the floriculturists, while in the rest of the individuals, a chemical related with the preparation of pesticides, such as additives, plasticizers, or solvents, was found. Our study shows that chronic exposure to pesticides produces DNA damage in floriculturists. It also suggests that this type of monitoring could be valuable in recommending preventive measures.

Genotoxic and cytotoxic studies of beta-sitosterol and pteropodine in mouse.

Beta-sitosterol (BS) and pteropodine (PT) are constituents of various plants with pharmacological activities potentially useful to man. The chemicals themselves possess biomedical properties related to the modulation of the immune and the nervous systems, as well as to the inflammatory process. Therefore, safety evaluation of the compounds is necessary in regard to their probable beneficial use in human health. The present study evaluates their genotoxic and cytotoxic potential by determining the capacity of the compounds to induce sister chromatid exchanges (SCE), or to alter cellular proliferation kinetics (CPK) and the mitotic index (MI) in mouse bone marrow cells. Besides, it also determines their capacity to increase the rate of micronucleated polychromatic erythrocytes (MNPE) in peripheral mouse blood, and the relationship polychromatic erythrocytes/normochromatic erythrocytes (PE/NE) as an index of cytotoxicity. For the first assay, four doses of each compound were tested: 200, 400, 600, and 1000 mg/kg in case of BS, and 100, 200, 300, and 600 mg/kg for PT. The results in regard to both agents showed no SCE increase induced by any of the tested doses, as well as no alteration in the CPK, or in the MI. With respect to the second assay, the results obtained with the two agents were also negative for both the MNPE and the PE/NE index along the daily evaluation made for four days. In the present study, the highest tested dose corresponded to 80% of the LD(50) obtained for BS and to 78% in the case of PT. The results obtained establish that the studied agents have neither genotoxic nor cytotoxic effect on the model used, and therefore they encourage studies on their pharmacological properties.

In vitro genotoxic evaluation of three alpha-asarone analogues.

alpha-Asarone has shown a significant capacity to reduce the level of lipids, including cholesterol. However, several toxic and genotoxic studies have determined that its use may pose a risk to human health. Therefore, a series of compounds structurally analogous to alpha-asarone were prepared in order to maintain the same pharmacological properties but with low toxicity. In this study we evaluated the potential of three alpha-asarone analogues to induce mutagenicity using the Ames test (strains TA98 and TA100 in the presence of metabolic activation), as well as the induction of sister chromatid exchanges (SCE) in cultured human lymphocytes. The tested compounds were: 1-(2,4,5-trimethoxyphenyl)propan-1-one (D1), 1-(2-chloro-4,5-dimethoxyphenyl)propan-1-one (D2), and 1-(4,5-dimethoxy-2-nitrophenyl)propan-1-ol (D3). The results in the first assay showed no mutagenic effect for the three tested analogues; in the TA100 strain, certain cytotoxicity did appear in the case of D2 and D3 only at high concentrations. In regard to the SCE assay, compounds D1 and D2 presented no statistical differences in comparison with the control culture values; however, the high dose of D3 (300 microg/ml) produced a significant increment in SCE (68% above the control value). With respect to the mitotic index and the cellular proliferation kinetics, we observed a reduction when compounds D2 and D3 were used at the higher concentrations. Our results encourage further preclinical studies of these compounds in both in vitro and in vivo models (particularly for analogues D1 and D2), to determine their toxicological profile and establish the possibility of using them in humans.

Antigenotoxic and antioxidant effect of grapefruit juice in mice treated with daunorubicin.

Grapefruit juice (GJ) is widely consumed in many countries. Several of its constituents possess nutritive value, as well as antigenotoxic and antioxidant effects. Therefore, the aim of this investigation was to evaluate the capacity of GJ to inhibit the micronucleated polychromatic erythrocytes (MNPE) produced by daunorubicin (Dau) in an acute assay in mice, as well as to determine its antioxidant potential in mouse hepatic microsomes, and its capacity to trap free radicals in vitro. In regard to the first point, GJ produced no toxic or genotoxic damage; on the contrary, it generated a significant reduction of the MNPE formed by Dau. The effect was found throughout the examined schedule (from 24 to 96 h). The two high doses produced inhibition of about 60% at 48 h, 86% at 72 h and 100% at 96 h after the treatment. With respect to the GJ antioxidant potential, a 50% decrease in liver microsomal lipid peroxidation produced by Dau was found by quantifying malondialdehyde formation. Finally, a strong GJ scavenging activity evaluated with the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) was observed, giving rise to a concentration-dependent curve with a correlation coefficient of 0.98. Overall, our results established an efficient anticlastogenic potential of GJ, probably related to its antioxidant capacity, or to alterations of Dau metabolism, suggesting the pertinence of extending research on the matter using other mutagens and biological models.