Polychromatic Erythrocytes Research Articles

Cytogenetic Effects of Carbendazim on Mouse Bone Marrow Cells

A study of the genotoxic activity of fungicide carbendazim was carried out. It was demonstrated that the tested technical grade active ingredient of carbendazim in the dose range of 125–2000 mg/kg body weight induced a statistically significant dose-dependent increase in the frequency of micronucleated polychromatic (PCE) and normochromatic erythrocytes (NCE) in the bone marrow of CD-1 mice. After administration of carbendazim at doses of 250–2000 mg/kg body weight, the accumulation of cells containing two or more micronuclei was observed. According to the results of comet assay, there was no increase in the level of breaks and alkali-labile sites in the DNA of the mouse bone marrow and liver cells after administration of technical grade carbendazim at doses up to 2000 mg/kg body weight. It is therefore suggested that the observed accumulation of cells with micronuclei is due to the aneugenic effect of carbendazim. In addition, a dose-dependent increase in the proportion of macrocytes/gigantocytes and dumbbell-shaped cells with constrictions among PCEs and NCEs was observed, which might be indicative of the inhibitory effect of the test pesticide on cytokinesis. The accumulation of polychromatophiles with pyknotic nuclei after exposure to carbendazim is probably caused by the distortion of nuclear extrusion. A possible general mechanism underlying the impairment of karyokinesis, cytokinesis, and nuclear extrusion in mammalian bone marrow erythroid cells is discussed.

THERAPEUTIC POTENCY OF SWEET ORANGE JUICE OVER LIVER GENOTOXICITY INDUCED BY PESTICIDE LANNATE IN RATS

Objective: The aim of the present investigation was to study the potential effect of sweet orange juice against liver genotoxicity induced by lannate.
 Methods: adult 36 female rats were divided into 6 groups: group C (control group), group L (lannate group) injected intraperitoneal (i. p.) with 1 mg/kg b. wt. lannate for one day, group J (orange juice group) orally administered a dose of 0.1 ml/10 g b. wt. of orange juice for 48 h, group J+L received the orange juice prior to lannate, group J with L received lannate in continuous with the orange juice and group L+J received lannate prior to the orange juice. Tested parameters were DNA fragmentation, micronucleus, histopathology examination and biochemical analysis.
 Results: it was found that, the intake of lannate caused high DNA fragmentation and significant increase (P<0.001) in the number of micronucleated polychromatic erythrocytes in the bone marrow. Furthermore, lannate exhibited some pathological changes in the liver tissues as well as a significant (P<0.001) decrease in the total antioxidative capacity (TAC) and a significant increase in the total oxidative capacity (TOC). On the other hand, orange juice administration of all treatments (pre-treatment, continuous and post-treatment) gave some amelioration against liver damage induced by lannate. While the best results were evidenced in the continuous treatment group where the juice could attenuate liver DNA fragmentation and significantly decreased (P<0.001) the number of micronucleated polychromatic erythrocytes. In addition, it improved the induced degenerative histopathological changes as well as ameliorated the changes occurred in TAC and TOC significantly (P<0.001).
 Conclusion: the antigenotoxic impact of orange juice against lannate was therapeutic and hence can counteract the poisonous effect of the pesticide in people who exposed to it.

Ethno Botanical Survey, Anti-leukemia and Anticlastogenic Potential of Medicinal Plants used for Treatment of Leukemia in Oyo State Nigeria

Ethnopharmacological Relevance: Leukemia, a cancer of the blood and bone marrow is responsible for about 222.000 deaths annually. The side effects of chemotherapy in leukemia treatment have necessitated the search for natural products especially medicinal plants as alternative therapy.
 Aim: This study surveyed common plants used for treating leukemia in Oyo state, Nigeria and assessed the anti-leukemic and anti-clastogenic activities of fractions of Nymphaea lotus.
 Methods: Semi-structured questionnaire (1000) was used to collect the ethnobotanical data among the traditional healers. Leukemia was induced in albino mice with 400 mg/kg body weight of benzene intraperitoneally. Aqueous extracts (120mg/kg/bw), fractions and 5-florouracil (25mg) was administered to mice of different groups. The anti-leukemic, anti-clastogenic, antioxidant, hepatoprotective activities and hematological parameters were determined. N. lotus was subjected to gas-chromatography mass spectroscopy analysis.
 Results: The ethnobotanical survey recorded 89 plant species with their local names and parts used in the traditional therapeutic preparations. Seven plants (Pistiastratiotes (2.5%), Nymphaea lotus (1.4%), Piper guineense (1.7%), Securinega virosa (2.5%), Calotropis procera (3.4%), Morinda lucida (2.5%) and Xylopia aethiopica (4.5%) with the highest frequency of citation were selected for anti-leukemic and anti-clastogenic screening. The aqueous extract of N. lotus and M. lucida displayed anti-leukemic potential. M. lucida and X. aethiopica improved the hematological parameters. Ethyl acetate fraction of N. lotus significantly (p<0.05) reduced the number of micronucleated polychromatic erythrocyte in the bone marrow and showed anti-leukemic activity. Fractions of N. lotus restored the hematological parameters and exhibited significant (p<0.05) antioxidant activity. Histological observation revealed improvement in the liver general cyto-architecture of mice treated with ethyl acetate and butanol fractions of N. lotus. Some known compounds were identified in ethyl acetate fraction of N. lotus.
 Conclusion: Most of the species tested had some anti-leukemic effect in mice, which to some extent supports their traditional inclusion in herbal preparations for treatment of leukemia. The study also identified potential anti-leukemic compounds in N. lotus extract. The study also identified potential anti-leukemic compounds in N. lotus extract.

Licochalcone A, a licorice flavonoid: antioxidant, cytotoxic, genotoxic, and chemopreventive potential

ABSTRACT Licochalcone A (LicoA) is a flavonoid derived from Glycyrrhiza spp. plants. The present study aimed to investigate the antioxidant, cytotoxic, genotoxic, and chemopreventive effects of LicoA in in vitro and in vivo systems. The results showed that LicoA (197.1 μM) scavenged 77.92% of free radicals. Concentrations of 147.75 µM or higher LicoA produced cytotoxicity in Chinese hamster ovary (CHO) fibroblasts. LicoA treatments of 4.43 to 10.34 µM did not exert genotoxic activity, but at 11.8 µM significantly lowered nuclear division indexes, compared to negative control, revealing cytotoxicity. Lower concentrations (1.85 to 7.39 µM) exhibited protective activity against chromosomal damage induced by doxorubicin (DXR) or methyl methanesulfonate (MMS) in CHO cells. LicoA exerted no marked influence on DXR-induced genotoxicity in mouse erythrocytes, but reduced pre-neoplastic lesions induced by 1,2-dimethylhydrazine (DMH) in rat colon at 3.12 to 50 mg/kg b.w. Biochemical markers and body weight indicated no apparent toxicity. These findings contribute to better understanding the mechanisms underlying LicoA-initiated activity as a promising chemopreventive compound. Abbreviations AC, aberrant crypts; ACF, aberrant crypt foci; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BOD, biochemical oxygen demand; CHO, Chinese hamster ovary fibroblast; DMH, 1,2-dimethylhydrazine; DMSO, dimethyl sulfoxide; DPPH, 2,2-diphenyl-1-picrylhydrazyl; DXR, doxorubicin hydrochloride; EDTA, ethylenediaminetetraacetic acid; GA, gallic acid; LicoA, licochalcone A; MMS, methyl methanesulfonate; MNBC, micronucleated binucleated cells; MNPCE, micronucleated polychromatic erythrocyte; NCE, normochromatic erythrocyte; NDI, nuclear division index; PBS, phosphate-buffered saline; PCE, polychromatic erythrocyte; XTT, 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide.

Ameliorative effects of hexane extract of Garcinia kola seeds Heckel (Clusiaceae) in cisplatin-induced hepatorenal toxicity in mice

Garcinia kola seed is used to manage liver diseases in ethnomedicine. However, there is limited information on its role in Cisplatin (CIS)-induced toxicity. Here, we investigated the potential of hexane extract of Garcinia kola (HEGK) in lessening CIS-induced hepatorenal- and gene- toxicity. Male mice (22 ± 3 g) randomly assigned into groups (n = 5) were treated for five days: Corn oil only, HEGK (200 mg/kg), CIS (20 mg/kg; i.p; 48-hours), CIS + HEGK (100 mg/kg), CIS + HEGK (200 mg/kg), CIS + Quercetin (25 mg/kg), and Quercetin(25 mg/kg). Corn oil, HEGK, and Quercetin were administered daily by gavage. GC-MS revealed the presence of 9,19-Cyclolanost-24-en-3-ol as the most abundant component in HEGK, with an LC50 of 1023 µg/mL. HEGK significantly (p < 0.05) scavenged DPPH, inhibited lipid peroxidation and exhibited reducing activity dose-dependently. CIS treatment increased (p < 0.05) urinary albumin and creatinine by 18 and 56%, respectively, serum levels of total bilirubin, creatinine, and hepatic transaminases, while albumin decreased (p < 0.05) by 57%. CIS treatment increased renal and hepatic malondialdehyde (MDA) levels by 67 and 70% individually, while the activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) levels were decreased (p < 0.05). Furthermore CIS-induced the formation of mononucleated polychromatic erythrocytes (mnPCEs) 150% in the bone marrow of mice. Histology revealed necrosis of hepatocytes, congestion of renal interstitial vessel, and hyperplasia of the Kupffer cells. Pretreatment with HEGK reduced the levels of MDA, mnPCEs, and increased the activities of antioxidant enzymes and restored GSH to levels comparable in control mice. Taken together, HEGK ameliorated CIS-toxicity via the activation of the antioxidative pathways and mitigated genotoxicity by mitigating mnPCEs formation in mice.

Evaluation of the Acute Toxicity and Genotoxicity of the Rice Biofortified with β-Glucan

To provide a scientific evaluation of the food safety of the rice biofortified with β-glucan. The acute toxicity and genotoxicity of the rice were evaluated by 14-day feeding experiment, Ames experiment, erythrocyte micronucleus test and mouse lymphoma thymidine kinase gene ( TK) mutation assay respectively. In the acute toxicity test, there was no obvious toxicity of rice biofortified with β-glucan, and no abnormality was found in anatomical observation. The median lethal dose (LD 50) to rats and mice wereall greater than 15 mg/kg, which belonged to the actual non-toxic level. Whether with S 9 activation or not, no genotoxicity was found to the tested strains TA97a, TA98, TA100, TA102 and TA1535. No induction of polychromatic erythrocytes and inhibition of bone marrow were found in erythrocyte micronucleus test. The results of TK gene mutation assay did not show the mutagenicity of β-glucan bioaugmentation rice. All results of the three genotoxicity tests were negative. Under the current experimental conditions, β-glucan biofortified rice showed no obvious acute toxicity and genotoxicity.

Genotoxicity evaluation using micronucleus test in Rattus norvegicus captured in urban ecosystems of Buenos Aires, Argentina.

The overall goal of the present study was to evaluate and compare the existence of genotoxic damage in Rattus norvegicus captured in sites with different levels of chemical mixtures along the Matanza-Riachuelo river basin(MRRB). For this, thirty-six wild rats (R. norvegicus) were captured from six different sites in the MRRB. Capture sites were characterized with concentrations of 20 parameters in surface water, including concentrations of metals and its soluble state and physicochemical parameters. To evaluate genotoxic damage in the rats, the bone marrow micronucleus test was performed. For this, the frequency of micronucleated polychromatic erythrocytes (MNPCE) was calculated based on the observation of 2000 polychromatic erythrocytes (PCE) per animal. Also, to detect possible cytotoxic effects, the PCE/TE (total erythrocytes) ratio in 1000 erythrocytes/animal was calculated. The frequency of MNPCE was positively associated with the highest concentration of chrome, lead, copper, biological oxygen demand, and chemical oxygen demand. Also, the decrease on PCE/TE ratio in bone marrow was related with increase of practically all metals and physicochemical parameters in surface water. The results of this study reveal that rats that live in the MRRB were exposed to concentrations of pollutants that can cause genotoxic damage, even though the concentrations of these pollutants are mostly below the safety standards. Therefore,this work highlights the importance of using methods that allowto integrate all environmental parametersin risk assessment, such as sentinel species.

Evaluation of Anti-Cytotoxic and Anti-Genotoxic Effects of Nigella sativa through a Micronucleus Test in BALB/c Mice.

Nigella sativa (N. sativa) is a medicinal plant used for its therapeutic pharmacological effects such as anti-inflammatory, antioxidant, anticancer, antidiabetic, and immunomodulation. This study explored the anti-cytotoxic and anti-genotoxic effect of N. sativa through a micronucleus test (MNT) of BALB/c mice peripheral blood. Using 6-to-8-week-old healthy male BALB/c mice, four groups were formed: (1) Control (sterile water), single-dose 2 mg/kg/intraperitoneal (i.p); (2) N. sativa oil, 500 mg/kg/24 h/7 days/i.p; (3) Cisplatin (CP), single-dose 2 mg/kg/subcutaneous (s.c); (4) N. sativa + CP with their respective dosage. When evaluating polychromatic erythrocytes (PCE), a biomarker of cytotoxicity, the group treated with N. sativa + CP experienced an increase in the frequency of PCE, which demonstrated the recovery of bone marrow and modulation of cell proliferation. The analysis of micronucleated polychromatic erythrocytes (MNPCE), an acute genotoxicity biomarker, showed similar frequency of MNPCE within the groups except in CP, but, in the N. sativa + CP group, the frequency of MNPCE decreased and then regulated. Finally, the frequency of micronucleated erythrocytes (MNE), a biomarker of genotoxicity, the supplementation of N. sativa oil did not induce genotoxic damage in this model. Thus, we conclude that N. sativa has both cytoprotective, genoprotective effects and modulates cell proliferation in BALB/c mice.

Evaluation of the antioxidant activity and mutagenicity of Brazil nut (Bertholletia excelsa Bonpl.).

This study evaluated the antioxidant capacity and the genotoxic and antigenotoxic effects of the fixed oil of B. excelsa Bonpl. in peripheral blood of Swiss mice. For the antioxidant capacity, were used the β-carotene/linoleic acid and DPPH methods. In the genotoxicity assay, were used healthy, 6-7 week old male Swiss mice, and there were six animals per group. For the genotoxic test, animals were treated with different concentrations of B. excelsa (500, 1.000 and 2.000 mg/kg body weight bw) in 0.5 mL orally. For the antigenotoxic test, animals were treated with predetermined concentrations, followed by intraperitoneal injection of doxorubicin (DXR 15 mg/kg bw) in 0.3 ml, in addition to the negative group (water) and dimethylsulfoxide (200 μL). Peripheral blood samples were collected 24 and 48 hours after the treatments. The frequency of micronucleated polychromatic erythrocytes (MNPCEs) was obtained from the analysis of 2.000 MNPCEs/animal. After data analysis, the conclusion was that the fixed oil of B. excelsa showed excellent protective activity by the β-carotene/linoleic acid method, demonstrated absence of genotoxic effect, and significant antigenotoxic effect according to the protocols and treatments performed in this study.

Antimicrobial potential, phytochemical profile, cytotoxic and genotoxic screening of Sedum praealtum A. DC. (balsam)

BackgroundSedum praealtum has been used for a long time in traditional medicine as an analgesic and anti-inflammatory agent. Its beneficial effects have been known since ancient times, when Latinos used it to treat sore and swollen eyes. This research evaluated the antimicrobial potential, the cytotoxic and genotoxic effects, and some chromatographic profiles of the hydroethanolic extract of leaves, stems and roots of S. praealtum.MethodsThe antimicrobial activities were carried out by broth microdilution and agar diffusion. In vitro cytotoxicity was evaluated by cell cultures of Aedes albopictus and the selectivity index (SI) was estimated: SI=CI50/MIC. Genotoxic and systemic toxic effects of S. praealtum leaves were analyzed by micronucleus assay in mice bone marrow. Chromatographic profiles and mass spectra were investigated by GC-MS.ResultsGram-positive (B. subtilis, B. cereus, M. luteus, E. faecalis and S. aureus) and gram-negative (E. coli, E. aerogenes, S. marcescens, P. aeruginosa, P. mirabilis and S. typhimurium) bacteria exhibited MICs ranging from 12.5–50 and 0–50 mg/ml, respectively. Sedum praealtum showed no efficacy against M. tuberculosis and M. bovis. Cytotoxicity (CI50) of S. praealtum was 4.22 and 5.96 mg/ml for leaves and stems, respectively, while its roots showed no cytotoxicity. Micronucleated polychromatic erythrocytes (MNPCEs) analyzes showed no differences between treatment doses (0.5–2 g/kg) and negative control (NaCl), but the PCE/NCE ratio (polychromatic erythrocyte/normochromatic erythrocyte) showed significant differences. Phytochemical screening identified thirteen compounds in the leaves, stems and roots of S. praealtum potentially associated with their biological activities.ConclusionsThis research comprises a first scientific study on genotoxicity, cytotoxicity and antimicrobial effects of S. praealtum (Balsam), and it provides an initial theoretical foundation for its comprehensive use. Results showed antibacterial action of S. praealtum against gram-positive bacteria and some gram-negative species (depending on the plant anatomical part), but ineffective antimycobacterial action. However, S. praealtum leaves and stems display potential cytotoxicity, contributing to the SI < 1 values. In addition, S. praealtum leaves exhibit no clastogenic and/or aneugenic effects, but it has systemic toxicity dose-independent.

Asetamipridin Fare Kemik İliği Hücrelerinde KA (Kromozomal Aberasyon) ve MN (Mikronükleus) Test Yöntemleri ile Genotoksik Etkisinin Araştırılması

In this study, we aimed to determine acetamipridine’s (ACE) genotoxic effect in mus musculus var. albinos bone marrow cells by chromosomal aberration (CA) and micronucleus (MN) analysis. Mice were divided into four groups. Group 1 determined as negative control (NC), group 2, 3 and 4 were determined as 5 mg/kg ACE, 10 mg/kg ACE, and 15 mg/kg ACE groups respectively. ACE was given orally for 14 days. CA, mitotic index (MI) and MN frequencies were determined in femoral cells. As a result, no genotoxic effects were observed in groups treated with 5-10 mg/kg ACE compared to negative control. CA rates of 15 mg/kg ACE group was determined to be high (P<0.001). In addition, MI ratio in the 15 mg/kg ACE group was lower than the control group. When the ratios of the polychromatic erythrocyte with micronucleus were examined, no significant difference was found between the 5 mg/kg and 10 mg/kg ACE groups and control group. However, a statistically significant increase in MNPCE rates was observed in the 15 mg/kg ACE group compared to control ones (P<0.001). It was concluded that ACE at 15 mg/kg dose was genotoxic-cytotoxic.

Effect of High-Dose Topical Minoxidil on Erythrocyte Quality in SKH1 Hairless Mice.

Simple SummaryIn any animal species, involuntary exposure to unknown agents may increase genetic material damage. This genetic damage can also induce the appearance of diseases such as cancer or other pathologies, including problems that can be passed on to the offspring of the damaged individual. For instance, living organisms may be affected due to the use of medications or exposure to certain chemical, physical, or biological agents which cause cell failure. This impaired function acts as an indicator that helps identify and evaluate damage in order to avoid or minimize it. In this work, excessive doses of a cosmetic drug for topical use in dermatological treatments, known as minoxidil, produced defects in the blood of hairless mice, particularly in red cells, indicating loss of DNA, a situation that may compromise life or the offspring by causing damage to their genetic material. It is important to consider that compounds may be tissue- or species-specific, although we cannot rule out the possibility that similar damage could occur in other animal species. Thus, excessive exposure to this compound should be prevented.SKH1 hairless mice are widely used in carcinogenesis and dermatology research due to their bare skin, as exposure to different agents is facilitated. Minoxidil is a cosmetic drug that is recognized as a mitogenic agent, and mitogens are suggested to have carcinogenic and mutagenic potential by inducing cell division and increasing the possibility of perpetuating DNA damage. Therefore, we hypothesized that the application of high doses of minoxidil to the skin of hairless mice would increase the number of micronucleated erythrocytes (MNEs) in peripheral blood. The objective of this study was to evaluate the topical administration of high doses of minoxidil on peripheral blood erythrocytes of SKH1 mice by means of micronucleus assay. Minoxidil was administered on the entire body surface of mice every 12 or 24 h. Minoxidil dosing every 24 h increased the number of micronucleated polychromatic erythrocytes (MNPCEs), and dosing every 12 h increased the number of MNEs and MNPCEs, as compared to baseline and the negative control group. No decrease in polychromatic erythrocyte frequencies was observed in the minoxidil groups. Therefore, topical application of high minoxidil doses to mice can produce DNA damage, as observed through an increase in the number of MNEs, without producing cytotoxicity, possibly due to its mitogenic effect.

Antivenom activity of Moringa oleifera leave against pathophysiological alterations, somatic mutation and biological activities of Naja nigricollis venom

Moringa oleifera is a plant that has several medicinal properties, however, there are dearth of scientific information on the antivenom activities. This study therefore focused on the neutralizing activities of ethanol leaves extract of M. oleifera against Naja nigricollis venom toxicity in rats. For the in vivo study, forty male Albino wistar rats weighing between 180 and 195 g were randomly divided into eight groups of five rats each. Group 1 were injected with normal saline. Groups 2–7 were envenomed by a single intraperitoneal injection of 1.0 mg/kg (LD50) of the venom while groups 2, 3, 4, 5 and 6 were treated with 100, 200, 300, 400 mg/kg of the extract and 0.2 ml of EchiTAB PLUS-ICP polyvalent antivenom, respectively. Group 7 was not treated post envenomation and group 8 was administered with plant extract only. Treatment with M. oleifera reversed acute anemia, significantly decreased (P<0.05) plasma levels of the liver enzymes compared to the untreated group. There was significant increase in the frequency of micronucleated polychromatic erythrocytes in the treated groups compared to the normal control. There was a dose dependent inhibition of the hemorrhage and hemolysis induced by the venom in the groups treated with extract. The clotting time was prolonged in groups treated with extract and antivenom compared to the untreated group. Also, the antibodies (IgG) titre was significantly higher (p < 0.5) in untreated group compared to other treated groups. The results obtained in this study indicated that M. oleifera possesses potent antivenom properties and emphasized its potential use for the treatment of snakebites.

The investigation of the possible antigenotoxic in vivo effects of pomegranate(Punica granatum L.) peel extract on mitomycin-C genotoxicity

The aim of this study was to investigate the possible antigenotoxic effects of the extract of pomegranate (Punica granatum L.) peel, which has high antioxidant activity against the genotoxic effects that mitomycin-C creates in the bone marrow cells of mice by a chromosomal aberration, mitotic activity, and micronucleus test system. There were six groups including a negative control group, positive control group (2 mg/kg mitomycin-C (MMC)), 150 mg/kg P. granatum L. (PG) peel extract, 300 mg/kg PG peel extract, 150 mg/ kg PG + MMC, and 300 mg/kg PG + MMC. The extract of pomegranate peel was given to mice by oral gavage for 15 days. At the end of day 15, 2 mg/kg MMC was intraperitoneally administered to the mice. Chromosomal aberration, mitotic activity, and micronucleus rates were determined in bone marrow cells of the mice, which were euthanized 24 h after this application. As a result of the observations carried out, it was determined that the chromosomal aberrations and micronucleus ratios in the MMC group were at the maximum level in terms of chromosomal aberration rates and micronucleated polychromatic erythrocytes; this rate decreased with 150 mg/kg PG and 300 mg/kg PG peel extract application with MMC, and PG peel extract applied with MMC significantly increased this decrease due to dose increase (P < 0.001). It was observed that MMC application decreased mitotic activity and polychromatic erythrocyte/ normochromatic erythrocyte ratios, while statistically these rates significantly increased in the groups administered peel extract with MMC when compared to the MMC group (P < 0.001). As a result, it was determined that the peel extract at the stated dose showed antigenotoxic effects against the genotoxicity caused by mitomycin-C in the bone marrow cells of mice.

Genotoxic potential of a novel PDE-4B inhibitor Apremilast by chromosomal aberration and micronucleus assay in mice

ObjectiveResearchers have confirmed that chronic administration of drugs at high doses causes genotoxicity which serve as first step in development of cancers. Apremilast, a phosphodiesterase-4 inhibitor is Food and Drug Administration (FDA) approved drug for Psoriatic Arthritis. The present study designed to conduct genotoxicity testing using the genotoxic study which give simple, sensitive, economical and fast tools for the assessment of damage of genetic material. MethodsTo conduct genotoxicity study of Apremilast, 60 Swiss albino male mice divided into 6 groups (n = 10). Group1 served as a normal control group without any treatment, Group 2 treated as a disease control and administered with cyclophosphamide 40 mg/kg, IP. Group 3, 4, 5 and 6 treated as test groups and received 10, 20, 40 and 80 mg/kg/day Apremilast respectively. The total duration of study was 13 weeks. At termination day animals were sacrificed and chromosomal aberration assay (BMCAA) and micronucleus assay (BMMNA) were performed to know the genotoxicity potential of Apremilast. ResultsThe results indicates significant rise in chromosomal aberrations (CA) frequency in bone marrow cells and decrease in the MI of the disease control animals as well as Apremilast treated groups. Further significant (p < 0.001; p < 0.0001) increase in score of micronucleated polychromatic erythrocytes (MNPCEs) and percentage of micronucleated PCEs per 1000 PCEs and decrease in the ratio of polychromatic/normochromatic erythrocytes (PCE/NCE) was observed in micronucleus assay. Genotoxic effect increases with the increase of Apremilast dose. Conclusion: Finding of present indicates that Apremilast shows genotoxic potential on high administration although further detailed toxicity studies required for confirmations.

Genotoxicity assessment of saline extract from Pilosocereus gounellei (Cactaceae) and its chemopreventive effect against cyclophosphamide-induced DNA damage

Pilosocereus gounellei (Cactaceae) is used to treat wounds and inflammation. In this study, we evaluated whether the saline extract from its stem would have genotoxic or anti-genotoxic effects. In the genotoxicity evaluation, mice received the extract (500, 1,000, or 2,000 mg/kg) orally while negative and positive controls were treated with saline solution (0.9% NaCl) per os and cyclophosphamide (CPA, 80 mg/kg i.p.), respectively. In the anti-genotoxicity assay, using other animals, treatments were carried out by administering the extract (500, 1,000 or 2,000 mg/kg) or saline solution (negative control) per os and then CPA (80 mg/kg i.p.) 1 h later. Genotoxic effects were evaluated by micronucleus test and comet assay using peripheral blood and bone marrow cells. Oral administration of only the extract at 500 and 1,000 mg/kg did not result in genotoxicity. A slight increase in the incidence of micronucleus was observed at the highest dose (2,000 mg/kg). Administration of the extract before CPA reduced the micronucleated polychromatic erythrocytes (MNPCE) number by 49.07–71.43%, and DNA fragmentation in peripheral blood (85.04–94.44%) and bone marrow (87.43–92.70%) cells also decreased. In conclusion, when administered orally at the tested doses, the extract is genotoxically safe, being cautious in doses above 1,000 mg/kg, and has a protective effect against CPA-induced DNA damage.

Anticlastogenic and Antidyslipidemic Activities of Jatropha Gossypifolia Leaf Extract on Female Rats Exposed to Cypermethrin

Though cypermethrin (Cyp) has contributed considerably to human welfare, their adverse effects on non‐target organisms are significant. The lipophilic nature of this pyrethroid exacerbates its toxicity by facilitating rapid access to the various tissues which in turn increase its interaction with the central nervous system, for which pesticides have high affinity. This study was designed to investigate the anticlastogenic and antidyslipidemic effects of Jatropha gossypifolia (JG), alpha‐lipoic acid (αLA) and vitamin C (VC) on plasma lipoprotein fractions in female rats. Eighty female rats were divided into ten groups of eight animals each and treated orally for 30 days. Groups 1 and 2 were given corn oil and cypermetrhin respectively, groups 3,4,5 and 6 were co‐administered with Cyp+JG50 mg/kg, Cyp+JG100 mg/kg, Cyp+αLA50 mg/kg and Cyp+VC50 mg/kg respectively. Groups 7, 8, 9 and 10 were given only JG50 mg/kg, JG100 mg/kg, αLA50 mg/kg and VC50 mg/kg respectively. From this study, cypermethrin administration resulted in an array of dyslipidemia as evidenced by significant increase in the level of cholesterol in plasma (64.05%), vLDL+LDL (571.88%), ovary (313.97%), uterus (147.49%); and triglyceride in plasma (88.69%), vLDL+LDL (71.51%), uterus (27.27%); however, a significant decrease was observed in ovary triglyceride (70.24%). Also, a significant increase was observed in the mean polychromatic erythrocyte (429.00%) compared to the control. Co‐administration with the methanolic leaf extract of JG, αLA and VC was able to attenuate the observed cypermethrin‐induced dyslipidemia and clastogenicity. Toxicological study from this study revealed that the plant extract is therapeutically safe for consumption at the doses under investigation. It can thus be concluded that the methanolic extract of Jatropha gossypifolia leaf could help regulate the dyslipidemic effect of cypermethrin on lipid parameters in organs and plasma lipoprotein fractions. The anticlastogenic effect of the plant could also be linked to the various phytoconstituents embedded in the plant.

Evaluation of the genotoxicity and teratogenicity of xylan using different model approaches

Xylan is the second most abundant polysaccharide group in plants and has a wide variety of food and pharmaceutical applications. However, little information on the safety assessment of extracted xylan as dietary supplement is available. As part of a comprehensive toxicological assessment, this study examined the potential toxicity of xylan extracted from sugarcane bagasse by three genotoxicity studies (Ames test, in vivo mice bone marrow micronucleus test, and mice sperm abnormality test) and a teratogenicity study in rats. In the Ames test, xylan showed no mutagenic activity on histidine dependent strains of Salmonella typhimurium at concentrations up to 5000 μg/plate; results of the in vivo mice bone marrow micronucleus test and mice sperm abnormality test indicated no significant effect on sperm morphology and micronucleus rate of polychromatic erythrocytes in mice at doses up to 5 g/kg body weight. In the teratogenicity study, a total of 60 pregnant rats were exposed to 10, 5, and 2.5% xylan in diet, from gestation days 7 to 16, and the no-observed-adverse-effect levels (NOAEL) of xylan was determined to be 9.8 g/kg body weight. The safe dose of xylan for human was estimated to be 98 mg/kg/day (i.e., 6.86 g/day for a 70-kg person), using a 100-fold safety factor. Taken together, results of this study indicated that xylan is practically nontoxic in terms of potential dietary consumption by humans in food or as a dietary supplement.

Dietary protection by Tapinanthus globiferus (Mistletoe) leaf extract against prontosil-induced clastogenicity in mice in vivo

Mistotoe (Tapinanthus globiferus) as freshly prepared leaf extract was administered at variable concentration (25, 50 and 100 mg/kg) per body weight as dietary supplement to laboratory albino mice via oral gavage for two weeks consecutively. The mice were also simultaneously administered 1.5 mg/kg pesticide precursor (Prontosil). 24 hours after the last day, the mice were sacrificed and chromosome preparations were made from the bone marrow cells. The end-points studied were polychromatic erythrocytes and damage cells. The results indicated that the clastogenicity in the mice fed with Tapinanthus globiferus leaf extract reduced significantly (P<0.05) compared to those fed with prontosil only. The marked reduction of clastogenicity by the extract may be attributed to the interaction with polyphenolic and phytochemical components of the extract.

Experimental simulation of somatic and germ cell genotoxicity in male Mus musculus fed extracts of lead contaminated Pleurotus ostreatus (white rot fungi).

Exposure to lead (Pb) is a major risk factor in reproductive toxicity, somatic, and germ cell genotoxicity. Exposure via deteriorating Pb paints and contaminated air, soil, and water had been the primary routes. However, with increasing reports of Pb accumulation in mushrooms and other food items may increase the etiology of Pb poisoning. The study herein investigated somatic genotoxicity and reproductive abnormalities in mice fed extracts of Pb-contaminated Pleurotus ostreatus. Male mice were fed aqueous extracts of P. ostreatus cultivated in 0, 10, 20, 100, 200, 500, and 1000mg/L of Pb-contaminated rice straw for 35days. Testes were analyzed for Pb accumulation, histopathology and relative weight gain, caudal epididymis for abnormal sperm morphology, and bone marrow for micronucleus test. Concentration-related significant increase in Pb accumulation was observed in P. ostreatus and testes of exposed mice. Decrease testicular weight, congestion of blood vessels, necrosis, and disorganization of the seminiferous tubules were observed in treated mice. In addition, fold increase of 2.78, 3.39, 6.67, 7.21, 9.63, and 9.70 in abnormal sperm morphology in accordance with the Pb concentrations respectively, confirmed reproductive toxicity. Significant increase in micronucleated polychromatic (PCE) and normochromatic (NCE) erythrocytes and concentration-related decrease PCE-NCE ratio in the bone marrow of treated mice suggest genome instability. Pb-contaminated P. ostreatus increased somatic and germ cell genotoxicity in mice. This may predispose the mice to genetic related syndromes and reproductive syndromes. It further suggests caution in the consumption of metal laden wild mushrooms and crop plants.