Captopril protects mice bone marrow cells against genotoxicity induced by gamma irradiation

The radioprotective effects of captopril were investigated by using the micronucleus test for anticlastogenic and cell proliferation activity. A single intraperitoneal administration of captopril at doses of 10, 25 and 50 mg/kg 1 h prior to gamma irradiation (2 Gy) reduced the frequencies of micronuleated polychromatic erythrocytes (MnPCEs). All three doses of captopril significantly reduced the frequencies of MnPCEs and increased polychromatic erythrocytes (PCE)/PCE+NCE (normochromatic erythrocyte) ratio in mice bone marrow compared to the non-drug-treated irradiated control (p < 0.001). The optimum dose for protection in mouse was 10 mg/kg to protect mice bone marrow 2.18-fold against the clastogenic effects of gamma-irradiation with respect to the non-drug-treated irradiated control. There was a drug dose-response effect of captopril in increasing the PCE/PCE+NCE ratio in bone marrow cells. The maximum protective effect of captopril was at a dose of 25 mg/kg for increasing the PCE/PCE + NCE ratio. Captopril exhibited concentration-dependent antioxidant activity, scavenging > 96% of the 1,1-diphenyl-2-picryl hydrazyl free radicals when used at a concentration of 0.2 mM. In this study captopril reduced lipid peroxidation induced by hydrogen peroxide in mice liver. It appears that captopril, due to its free radical scavenging properties, protects mice bone marrow cells from radiation-induced DNA damage and genotoxicity.     

Multi-endpoint biological monitoring of phosphine workers

5-Aminosalicylic acid (5ASA), a prescribed drug for ulcerative colitis, is a potent scavenger of oxygen-derived free radicals. The present study was undertaken to ascertain its ability to protect against radiation-induced damage. The drug dose-dependent effect, optimum time of drug administration and radiation dose-dependent effect (0-4 Gy) on in vivo radiation protection against micronuclei induction in polychromatic erythrocytes (PCE) and normochromatic erythrocytes (NCE) were studied in the bone marrow of mice. Intraperitoneal injection of 10-125 mg/kg of the drug 30 min before whole body irradiation with 3 Gy produced a significant reduction in the frequency of micronucleated erythrocytes at 24 h after exposure. The optimum dose for protection without drug toxicity was 25 mg/kg body weight. Injection of 25 mg/kg of the drug 60 or 30 min before or within 15 min after 3 Gy whole body gamma-irradiation resulted in a significant decrease in the radiation-induced PCE and NCE with micronuclei (MPCE and MNCE) and an increase in the ratio of PCE to NCE (P/N), at 24 h post-irradiation. Maximum effect was seen when the drug was administered 30 min before irradiation. Therefore, to study the radiation dose-response, mice were pre-treated with 25 mg/kg of 5ASA 30 min before 1-4 Gy of gamma-irradiation. Radiation increased the MN frequency linearly (r(2)=0.99) with dose. Pre-treatment with 5ASA significantly reduced the MN counts to 40-50% of the radiation (RT) alone values, giving a dose modification factor (DMF) of 2.02 (MPCE) and 2.53 (MNCE). Irradiation resulted in a dose-dependent decline in the P/N ratio at all the doses of radiation studied. 5ASA produced a significant increase in the P/N ratio from that of irradiated controls, at all doses of radiations tested. These results show that 5ASA protect mice against radiation-induced MN formation and mitotic arrest.     

Vinblastine treatment induces dose-dependent increases in the frequency of micronuclei in mouse bone marrow.

The effect of various doses (0.005-2.0 mg/kg b.w.) of vinblastine sulfate (VBL) was studied on the induction of micronuclei in polychromatic and normochromatic erythrocytes (PCE, NCE) of the bone marrow of female BALB/c mice. VBL treatment resulted in a dose-dependent increase in the frequency of micronucleated PCE and NCE, while the PCE/NCE ratio and mitotic index declined with increasing drug dose. The dose-effect curves were linear quadratic for all the parameters studied.     

Chemoprotective effects of carnosine against genotoxicity induced by cyclophosphamide in mice bone marrow cells

The protective effects of carnosine as a natural dipeptide were investigated in mouse bone marrow cells against genotoxicity induced by cyclophosphamide. Mice were injected with solutions of carnosine at three different doses (10, 50 and 100?mg kg(-1) bw) for five consecutive days. On the fifth day of treatment, mice were injected cyclophosphamide and killed after 24?h. The frequency of micronuclei in polychromatic erythrocytes and the ratio of polychromatic erythrocyte/polychromatic erythrocyte?+?normochromatic erythrocyte [PCE/(PCE?+?NCE)] were evaluated by May-Grunwald/Giemsa staining. Histopathology of bone marrow was examined in mice treated with cyclophosphamide and carnosine. Carnosine significantly reduced micronucleated polychromatic erythrocytes (MnPCEs) induced by cyclophosphamide at all three doses. Carnosine at dose of 100?mg kg(-1) bw reduced MnPCEs 3.76-fold and completely normalized the PCE/(PCE?+?NCE) ratio. Administration of carnosine inhibited bone marrow toxicity induced by cyclophosphamide. It appeared that carnosine with protective activity reduced the oxidative stress and genotoxicity induced by cyclophosphamide in bone marrow cells of mice. Copyright ? 2012 John Wiley & Sons, Ltd.     

Absence of antimutagenicity of Cochlospermum regium (Mart. and Schr.) Pilger 1924 by micronucleus test in mice.

Cochlospermum regium (Mart. and Schr.) Pilger, popularly known as "algod?ozinho do campo", is a medicinal plant that grows in the Cerrado of Brazil. This plant has been used in traditional medicine against various diseases such as leucorrhoea, gastritis and ulcers. It has also been effective in treating skin problems like pimples, boils and blotches. In the present study, the in vivo antimutagenicity of aqueous extract of C. regium was evaluated. The Micronucleus Test was performed in polychromatic erythrocytes from Swiss male mice treated with one of the four doses of extract of the plant (19, 38, 76 and 114 mg.kg(-1) body weight), administered by intraperitonial injection (i.p.) simultaneously with cyclophosphamide (24 mg.kg(-1) b.w.) or mitomycin C (4 mg.kg(-1) b.w.). The cytotoxicity was evaluated by polychromatic and normochromatic erythrocytes ratio (PCE/NCE). The results showed no significant reduction of the micronucleated polychromatic erythrocytes frequency (P > 0.05). In conclusion, the data indicate that C. regium roots aqueous extract, for the conditions used, did not exhibit the antimutagenic effect.     

Effect of 6-nonadecyl salicylic acid and its methyl ester on the induction of micronuclei in polychromatic erythrocytes in mouse peripheral blood

The bark of Amphipterygium adstringens is widely used in the traditional Mexican medicine for treating ailments such as gastric ulcers, gastritis and stomach cancer. The 6-nonadecyl salicylic acid (anacardic acid) was isolated from the bark of this species. In previous papers have been informed that the anacardic acids possess anti-tumour, antimicrobial, antiacne, antibacterial and many others medicinal properties. Now we describe cytotoxic and genotoxic effects of this compound and its methyl ester. The cytotoxic and genotoxic effects of 6-nonadecyl salicylic acid (6NDSA) and its methyl ester (ME6NDSA) on CD1 male mice were determined with micronucleus assay at 24, 48 and 72h after oral administration of doses of 0.75, 2.5, 5.0 and 10.0mg/kg. Peripheral blood samples were drawn from the caudal vein and analyzed by Giemsa-stained technique. The results obtained showed that the ratios of polychromatic erythrocytes (PCE) to normochromatic erythrocytes (NCE) in mice treated with 10mg/kg of 6NDSA were statistically lower after 24h compared with its negative control animals, and that after 72h, PCE/NCE ratios were reduced in animals treated with 6NDSA at all tested dose levels. The methyl ester ME6NDSA showed no such cytotoxic activity. Neither of the test compounds increased the frequency of micronucleated polychromatic erythrocytes from which it appears that administration of 6NDSA and ME6NDSA may not lead to chromosome damage at the evaluated doses.     

Protective effect of Hemidesmus indicus R.Br. root extract against cisplatin-induced cytogenetic damage in mouse bone marrow cells

The aqueous extract of Hemidesmus indicus roots was investigated for its in vivo antigenotoxic effect against cisplatin-induced cytogenetic damage. Swiss albino mice were administered with various doses of the extract either singly (50, 100 and 200 mg/kg body weight) or as split doses (10, 20 and 40 mg/kg bw/day) for five consecutive days by oral gavage. As endpoints, chromosome aberrations, micronuclei in polychromatic erythrocytes, mitotic index and PCE/NCE ratio were estimated. The extract protected the bone marrow cells from cisplatin-induced genotoxicity in an inverse dose-dependent manner. However, the extract was cytotoxic at all doses. But, under split dose regime it conferred a higher level of genoprotection and was not cytotoxic at the lower two doses. The presence of saponins, tannins, phenols, terpenoids, flavonoids and coumarins in the crude extract could explain these effects.     

Assessment of the mutagenic, antimutagenic and cytotoxic activities of ethanolic extract of araticum (Annona crassiflora Mart. 1841) by micronucleus test in mice.

A typical Brazilian plant, araticum (Annona crassiflora Mart.), is widely used in humans as therapeutic medicine to treat several diseases such as diarrhea, rheumatism and syphilis. It contains acetogenins which present cytotoxic, antitumogenic, and antiparasitic properties. In this study, mutagenic, antimutagenic and cytotoxic effects of araticum leaves ethanolic extract were evaluated by micronucleus test in mice. To evaluate the mutagenic activity, animals were treated with ethanolic extract of araticum (EEA) using 10, 20, 50, 100 and 160 mg.kg(-1). For all doses, micronucleated polychromatic erythrocytes (MNPCE) frequency was evaluated at 24, 48 and 72 hours after treatment. To evaluate the antimutagenic activity, animals were treated with 10, 20, 50 and 100 mg.kg(-1) of EEA and 4 mg.kg(-1) of MMC simultaneously. The frequency of MNPCE was evaluated 36 hours after exposure. Cytotoxicity was evaluated by the polychromatic and normochromatic erythrocytes ratio (PCE/NCE). In the mutagenicity assessment, all doses of EEA resulted in no significant increase of MNPCE (P > 0.05), compared to solvent- control group. Regarding administration time, no significant difference among three evaluation periods was observed (P > 0.05). Such results indicate that EEA did not exert mutagenic activity. Cytotoxicity was evident in doses of 50, 100 and 160 mg.kg(-1) at 24 and 48 hours after exposure. Concerning antimutagenicity, except the 10 mg.kg(-1) co-administered with 4 mg/kg of MMC, all doses reduced significantly the frequency of MNPCE compared to the positive control group (P < 0.05). These results, therefore, indicate an antimutagenic activity of the EEA. Cytotoxicity was significantly increased (P < 0.01) at 100 mg.kg(-1) EEA doses co-administered with 4 mg.kg(-1) of MMC.     

Primary pharmacological screening of an endemic plant from the Southern Morocco (Tetraena gaetula [Emb. & Maire] Beier & Thulin)

Tetraena gaetula (Emb. & Maire) Beier & Thulin (Zygophyllum gaetulum Emb. & Maire, Zygophyllaceae) is an endemic plant from the southern Morocco. This plant is widely used in Moroccan traditional medicine as an antispasmodic and antidiabetic. Our work aims to evaluate several pharmacological properties of extracts of T. gaetula such pro- or antiproliferative, immunomodulatory, analgesic and antidepressant effects. Initially, we studied intraperitoneally the acute toxicity of aqueous extract of T. gaetula in mice; the lethal dose 50 is 1.2 g/kg of body weight. Our results also showed a stimulating proliferative activity of T. gaetula, particularly at 6 μg/μL of the proteic extract on T lymphocytes. However, this same concentration of proteic extract induced rather cytotoxicity on B cells and macrophages. Our ex vivo results showed a dose-dependent response: (i) stimulation of lymphocyte subpopulations and monocytes in a dose 600 mg/kg, and (ii) immunosuppression at a dose 300 mg/kg. The pharmacological results in vivo showed a pronounced antidepressant effect of the proteic extract at all doses. However, the aqueous extract showed analgesic and anti-depressant effects, mainly at doses 300 and 600 mg/kg.     

Influence of Feeding Schedule on Chronopharmacological Aspects of Gentamicin in Mice

The effects of the time of day of drug administration on the subchronic toxicity and pharmacokinetics of gentamicin, as well as the role of feeding schedule on circadian rhythms, were investigated in mice. ICR male mice were housed in a light-dark (LD) cycle (12:12) with food and water ad libitum (ALF) or under a time-restricted feeding (TRF) schedule (feeding time: 8 h during the light phase) for 1 day or 14 days before drug administration. The animals were given a single subcutaneous dose of gentamicin 180 mg/kg for the kinetic studies and subcutaneous doses of gentamicin 180 mg/kg/day for 14 days or 220 mg/kg/day for 18 days for the subchronic toxicity studies. A significant dosing-time dependency was shown for mortality and body weight loss, with higher values at midlight and lower ones at the middark (p > 0.05). A significant circadian rhythm was also found for gentamicin kinetics in ALF mice, with the highest clearance at middark and the lowest one at midlight (p > 0.01). The kinetic rhythm of gentamicin coincided well with the toxicity rhythm of the drug. The TRF schedule had a marked influence on the rhythms of gentamicin kinetics and toxicity, showing lowest clearance and higher toxicity at middark. The rhythm of subchronic toxicity of gentamicin seems to be due, at least in part, to the rhythm in kinetics and is strongly influenced by the feeding schedule. Thus, the timing of dosing is an important factor in the kinetics and the subchronic toxicity of gentamicin administration in mice, and the manipulation of feeding schedule can modify the rhythm of the toxicity by changing the rhythm of gentamicin kinetics.     

In vivo radioprotective potential of thymol, a monoterpene phenol derivative of cymene

The radioprotective and anticlastogenic potential of a phenol derivative monoterpene thymol(TOH), against whole-body gamma radiation was studied in Swiss albino mice. Acute toxicity of TOH, with an LD(50(14)) of 1134.03mg/kgbwt., was observed when administered intra-peritoneally (i.p.). The radioprotective potential of TOH was evaluated using the optimal dose of 10mg/kgbwt. TOH, which increased the LD(50/30) by 2.17Gy and resulted in a dose reduction factor (DRF) of 1.25. A significant (p<0.01) reduction in micronucleated, polychromatic erythrocytes (PCE), normochromatic erythrocytes (NCE), and an increased PCE/NCE ratio was also observed after administration of 10mg/kg.b.wt. TOH prior to gamma radiation, indicating its antigenotoxic effect. TOH pre-treatment significantly (p<0.01) elevated reduced glutathione, glutathione-S-transferase, catalase, and superoxide dismutase levels and decreased lipid peroxidation levels in mouse liver homogenates at 24 and 48h after exposure to 4.5Gy of radiation. Further, TOH treatment before exposure to 7.5Gy of gamma radiation resulted in a significant (p<0.01) increase in hematological parameters at various post-treatment time points, with increased numbers of endogenous spleen colonies as well. The histological observations indicated a decline in villus heights and crypt numbers in mouse jejunum and were accompanied by a significant decrease in bone marrow nucleated cells in the irradiated group, which was almost normalized by pre-treatment with TOH. Our study clearly documents the antioxidant, anticlastogenic and radioprotective potentials of TOH, which may be attributed to several possible mechanisms, such as normalization of intracellular antioxidant levels and free radical scavenging activities by TOH.     

The genetic toxicity of 3,3',4,4'-tetrachloroazobenzene and 3,3',4, 4'-tetrachloroazoxybenzene: discordance between acute mouse bone marrow and subchronic mouse peripheral blood micronucleus test results

3,3',4,4'-Tetrachloroazobenzene (TCAB) and 3,3',4, 4'-tetrachloroazoxybenzene (TCAOB) are dioxin-like chemicals that were investigated for toxicity in 13-week gavage studies in male and female B6C3F(1) mice and F344N rats by the National Toxicology Program. As part of the comprehensive toxicological investigation of these chemicals, peripheral blood smears from mice treated 5 days per week for 13 weeks with 0.1-30mg/kg/day TCAB or TCAOB were analyzed for the frequency of micronucleated (MN) normochromatic erythrocytes (NCE). Both chemicals produced significant increases in MN-NCE in male and female mice. In contrast to these positive results in subchronic exposure studies, no significant increases were seen in acute bone marrow MN tests in male mice administered three daily injections of 50-200mg/kg/day TCAB and TCAOB. The results with TCAB and TCAOB suggest that the routine integration of MN tests with subchronic toxicity studies may allow detection of mutagenic activity for some chemicals that fail to elicit responses in short-term, high dose tests. In addition, the integration of mutagenicity tests into general toxicity tests reduces the use of laboratory animals and the cost of the testing.     

Benzophenone guttiferone A from Garcinia achachairu Rusby (Clusiaceae) Presents Genotoxic Effects in Different Cells of Mice

Benzophenones from natural sources and those of synthetic analogues present several reports of potent biological properties, and Guttiferone A represents a promising medicinal natural compound with analgesic and gastroprotective profiles. Considering that there are no reports that assess the genetic toxicity of Guttiferone A, the present study was undertaken to investigate the genotoxic potential of this benzophenone isolated from seeds of Garcinia achachairu in terms of DNA damage in different cells of Swiss albino mice using the comet assay, and its clastogenic/aneugenic effects in bone marrow cells in vivo by the micronucleus test. Cytotoxicity was assessed by scoring polychromatic (PCE) and normochromatic (NCE) erythrocytes ratio. Guttiferone A was administered by oral gavage at doses of 15, 30 and 60 mg/kg. The results showed that Guttiferone A produced genotoxic effects in leukocytes, liver, bone marrow, brain and testicle cells and clastogenic/aneugenic effects in bone marrow erythrocytes of mice. The PCE/NCE ratio indicated no cytotoxicity. Since guttiferone A is harmful to the genetic material we suggest caution in its use by humans.     

Assessment of the genotoxicity of propineb in mice bone marrow cells using micronucleus assay

Propineb, a dithiocarbamate fungicide, is commonly used for the control of disease in a wide range of crops in agriculture. The genotoxic effects of commercial formulation of propineb in bone marrow cells of mice was investigated in vivo by micronucleus (MN) assay. The three different concentrations of propineb (12.5, 25 and 50 μg/mL; 0.01 mL per gram) were injected intraperitoneally (i.p.) to mice for 24 and 48 h. The results of the MN assay indicated that propineb induced a significant increase in frequency of micronucleated polychromatic erythrocytes (MNPCE) at 25 and 50 μg/mL concentrations for 24 h and at the highest (50 μg/mL) concentration for 48 h when compared with negative control. Also significant reduction for the polychromatic erythrocyte/normochromatic erythrocyte (PCE/NCE) ratio which is indicative for bone marrow cytotoxicity was observed at the same concentrations for 24 and 48 h. These results lead us to the conclusion that propineb may have genotoxic and cytotoxic potential due to induction in the frequency of MN and a reduction in PCE/NCE ratio in the bone marrow cells of mice.     

Hepatoprotective effect of aqueous extract of Phyllanthus niruri on nimesulide-induced oxidative stress in vivo

Nimesulide (NIM), an atypical non-steroidal anti-inflammatory drug (NSAID) is also used as analgesic. In the present study, we evaluated its effect on the prooxidant-antioxidant system of liver and the hepatoprotective potential of aqueous extract of the herb Phyllanthus niruri (PN) on NIM-induced oxidative stress in vivo using a murine model, by determining the activities of hepatic anti-oxidant enzymes superoxide dismutase (SOD) and catalase (CAT), levels of reduced glutathione (GSH) and lipid peroxidation (expressed as malonaldialdehyde, MDA). Aqueous extract of PN at a dose of 50 or 100 mg/kg body wt was administered either intraperitoneally or orally for 7 days, before NIM administration at a dose of 8 mg/kg body wt twice daily for 7 days in mice. Animals were sacrificed 24 h after administration of final dose of NIM. In another set of experiments, both aqueous extract of PN (at a dose of 50 or 100 mg/kg body wt) and NIM (8 mg/kg body wt) were administered simultaneously for 7 days. Animals were sacrificed 24 h after administration of final dose of the extract and NIM, liver tissues were collected, and the activities of SOD and CAT and levels of GSH and lipid peroxidation end-product (as MDA), were determined from the livers of all the experimental animals. Appropriate NIM control was maintained for all sets of experiments. NIM administration (8 mg/kg body wt) for 7 days caused significant depletion of the levels of SOD, CAT and reduced GSH, along with the increased levels of lipid peroxidation. Intraperitoneal administration of the extract at a dose of 50 mg/kg body wt for 7 days,. prior to NIM treatment, significantly restored most of the NIM-induced changes and the effect was comparable to that obtained by administering 100 mg/kg body wt of the extract orally. Thus, results suggested that intraperitoneal administration of the extract could protect liver from NIM-induced hepatic damage more effectively than oral administration. Antioxidant property of the aqueous extract of PN was also compared with that of a known potent antioxidant, vitamin E. The PN extract at a dose of 100 mg/kg body wt along with NIM was more effective in suppressing the oxidative damage than the PN extract at a dose of 50 mg/kg body wt. Results suggested that beneficial effect of the aqueous extract of PN, probably through its antioxidant property, might control the NIM-induced oxidative stress in the liver.     

Anti-ulcerogenic and analgesic activities of the leaves of Wilbrandia ebracteata in mice.

Wilbrandia ebracteata (Cogn.) Cogn. is a medicinal plant belonging to the Cucurbitaceae family used popularly as an antiulcer and analgesic medicine. The hydromethanol extract of leaves was investigated to determine its anti-ulcerogenic (ethanol and indomethacin induced gastric damage) and analgesic (writhing and tail-flick tests) activities in mice (efficacy), its acute toxicity (safety), and its phytochemistry (quality control). Oral administration of leaf extract at a dose of 1000 mg/kg body wt. significantly reduced 73.3% of the total area of lesion in ethanol-induced gastric damage, but was inactive in an indomethacin-induced gastric damage test. The hydromethanol extract was also inactive in both analgesic tests. Oral administration of the leaf extract did not produce mortality in mice, while the LD50 value of the roots was 22.10 mg/kg body wt. in female mice and 58.31 mg/kg body wt. in male mice. Leaves of W. ebracteata reacted positively for steroids, flavonols, flavanones, saponins, tannins and xanthones and negative for other compounds, including cucurbitacins. Leaf extract of W. ebracteata was active as an anti-ulcerogenic, probably through increasing gastric defensive factors, and flavonoids might be the main constituent responsible for this activity.     

Toxicological Evaluation of Lactase Derived from Recombinant Pichia pastoris

A recombinant lactase was expressed in Pichia pastoris, resulting in enzymatic activity of 3600 U/mL in a 5 L fermenter. The lactase product was subjected to a series of toxicological tests to determine its safety for use as an enzyme preparation in the dairy industry. This recombinant lactase had the highest activity of all recombinant strains reported thus far. Acute oral toxicity, mutagenicity, genotoxic, and subchronic toxicity tests performed in rats and mice showed no death in any groups. The lethal dose 50% (LD₅₀) based on the acute oral toxicity study is greater than 30 mL/kg body weight, which is in accordance with the 1500 L milk consumption of a 50 kg human daily. The lactase showed no mutagenic activity in the Ames test or a mouse sperm abnormality test at levels of up to 5 mg/plate and 1250 mg/kg body weight, respectively. It also showed no genetic toxicology in a bone marrow cell micronucleus test at levels of up to 1250 mg/kg body weight. A 90-day subchronic repeated toxicity study via the diet with lactase levels up to 1646 mg/kg (1000-fold greater than the mean human exposure) did not show any treatment-related significant toxicological effects on body weight, food consumption, organ weights, hematological and clinical chemistry, or histopathology compared to the control groups. This toxicological evaluation system is comprehensive and can be used in the safety evaluation of other enzyme preparations. The lactase showed no acute, mutagenic, genetic, or subchronic toxicity under our evaluation system.     

The genetic toxicity of 3,3′,4,4′-tetrachloroazobenzene and 3,3′,4,4′-tetrachloroazoxybenzene: discordance between acute mouse bone marrow and subchronic mouse peripheral blood micronucleus test results

3,3′,4,4′-Tetrachloroazobenzene (TCAB) and 3,3′,4,4′-tetrachloroazoxybenzene (TCAOB) are dioxin-like chemicals that were investigated for toxicity in 13-week gavage studies in male and female B6C3F₁ mice and F344N rats by the National Toxicology Program. As part of the comprehensive toxicological investigation of these chemicals, peripheral blood smears from mice treated 5 days per week for 13 weeks with 0.1–30 mg/kg/day TCAB or TCAOB were analyzed for the frequency of micronucleated (MN) normochromatic erythrocytes (NCE). Both chemicals produced significant increases in MN-NCE in male and female mice. In contrast to these positive results in subchronic exposure studies, no significant increases were seen in acute bone marrow MN tests in male mice administered three daily injections of 50–200 mg/kg/day TCAB and TCAOB. The results with TCAB and TCAOB suggest that the routine integration of MN tests with subchronic toxicity studies may allow detection of mutagenic activity for some chemicals that fail to elicit responses in short-term, high dose tests. In addition, the integration of mutagenicity tests into general toxicity tests reduces the use of laboratory animals and the cost of the testing.     

Genotoxic action of Luna Experience-SC 400 fungicide on rat bone marrow

Abstract

Background: Fungicides describe all chemicals used to control fungi that infect plants. Luna Experience SC-400 is a new line of fungicide that consist of Fluopyram and Tebuconazole.

Objective: In this study, We investigated the genotoxicty and cytotoxicty of Luna Experience-SC 400 using comet assay, micronucleus test and polychromatic erythrocytes number in rat bone marrow. The present study is the first report indicating the effects of genotoxic and cytotoxic of Luna experience SC-400 on rat bone marrow cells.

Material and Methods: We used three different doses (5mg/kg, 10mg/kg, 20mg/kg) of Luna Experience SC 400 at 48 h intervals during 30 days by gavage in rats.Genotoxicity was evaluated using comet assay and micronucleus test and cytotoxicity was measured the PCE/NCE rate in rat bone marrow.

Results: Based on these experimental results, we report that Luna Experience-SC 400 fungicide presents genotoxic and cytotoxic potential on rat bone marrow. There is a significant difference between negative control group and all the doses of Luna Experience-SC 400 (p?<?0.05) for comet assay and micronucleus. Even moderate and high doses of fungicides seem to have reached the values of almost positive control group for Genetic Damage Index (GDI) and Damaged Cell Percentage (DCP). In this study, we also investigated the PCE/NCE rate. Fungicide caused a decrease in the level of significant in the PCE/NCE ratio (p?<?0.05).

Conclusion: Our in vivo study suggests that the gavage exposure to Luna experience SC 400 used in the present investigation may be genotoxic and cytotoxic in rat bone marrow in view of these findings. Because this findings is first report represented in the pesticide biology, it is important to carry out more investigations using various cytogenetic tests under different experimental conditions to definitively resolve the the possible genotoxic and cytotoxic risk associated with new generation pesticides-fungicides.     

Influence of Griffonia simplicifolia on male sexual behavior in rats: Behavioral and neurochemical study

The seeds of Griffonia simplicifolia Baill. are rich in 5-HTP (5-hydroxytryptophan), a direct precursor of the neurotransmitter serotonin. In the present study we investigated the influence of the plant extract on male sexual behavior. The seed extract was orally administered to Sprague-Dawley male rats at three dose levels (25, 50 and 100 mg/kg) both acutely and subchronically (daily for 9 days). Mating test with receptive female rats was performed 60 min after the acute treatment or the last dose when repetitively administered. Mount, intromission and ejaculation latencies and post-ejaculatory interval were recorded. Food intake and body weight were measured over the 9-day period of treatment. Microdialysis technique was used to detect the extracellular levels of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in rat brain following the acute administration of the extract dosed at 100 mg/kg. The acute treatment significantly increased mount latency (at any dosage), intromission and ejaculation latencies (at 100 mg/kg) and post-ejaculatory interval (at 50 and 100 mg/kg). On the contrary the subchronic treatment failed to exert a significant influence on copulatory behavior. The daily administration of the extract dosed at 50 and 100 mg/kg for 9 days significantly reduced food intake and body weight. Finally in the microdialysis experiments we found a dramatic increase in 5-HT and its metabolite 5-HIAA.