Micronuclei In Bone Marrow Cells Research Articles

Safety and efficacy evaluation of halicin as an effective drug for inhibiting intestinal infections.

Halicin, the first antibacterial agent discovered by artificial intelligence, exerts broad-spectrum antibacterial effects and has a unique structure. Our study found that halicin had a good inhibitory effect on clinical isolates of drug-resistant strains and Clostridium perfringens (C. perfringens). The safety of halicin was evaluated by acute oral toxicity, genotoxicity and subchronic toxicity studies. The results of acute toxicity test indicated that halicin, as a low-toxicity compound, had an LD50 of 2018.3mg/kg. The results of sperm malformation, bone marrow chromosome aberration and cell micronucleus tests showed that halicin had no obvious genotoxicity. However, the results of the 90-day subchronic toxicity test indicated that the test rats exhibited weight loss and slight renal inflammation at a high dose of 201.8mg/kg. Teratogenicity of zebrafish embryos showed that halicin had no significant teratogenicity. Analysis of intestinal microbiota showed that halicin had a significant effect on the intestinal microbial composition, but caused a faster recovery. Furthermore, drug metabolism experiments showed that halicin was poorly absorbed and quickly eliminated in vivo. Our study found that halicin had a good therapeutic effect on intestinal infection model of C. perfringens. These results show the feasibility of developing oral halicin as a clinical candidate drug for treating intestinal infections.

In Vivo Genotoxicity Evaluation of a No-Pain Pharmacopuncture Extract Using the Micronucleus Test.

We aimed to evaluate the genotoxicity of a recently developed no-pain pharmacopuncture (NPP) targeting muscle relaxation and analgesia using the micronucleus test. To evaluate the potential of NPP extracts to induce micronuclei in rat bone marrow cells, a micronucleus test was performed using male Sprague-Dawley rats. The test substance NPP was administered intramuscularly at concentrations of 0.25, 0.5, and 1 mL/animal. Saline was used as the negative control and cyclophosphamide as the positive control. No NPP treatment-related deaths or abnormal changes in general appearance were observed at any dose level during the experimental period. No statistically significant differences in body weight were observed in any of the NPP dose groups compared to the saline negative control group. NPP did not cause a significant increase in the incidence of micronucleated polychromatic erythrocytes (PCEs) and PCEs or in the ratio of PCE-to-total erythrocytes. The NPP extract did not exhibit genotoxic in Sprague-Dawley rat bone marrow cells under the conditions of this study. Further toxicity studies of the NPP extract are required.

Acute, chronic, and genotoxic studies on the protopine total alkaloids of the Macleaya cordata (willd.) R. Br. in rodents.

The protopine alkaloids are widely distributed within the opium poppy family and have a wide range of pharmacological effects. MPTA is a product of the protopine total alkaloids extracted from the Macleaya cordata (Willd.) R. Br. Previously, we reported good anti-inflammatory activity of MPTA as well as oral acute and sub-chronic toxicity studies in rats. In order to perform a systematic toxicological safety assessment of MPTA, oral acute toxicity, genotoxicity (bone marrow cell chromosome aberration test, sperm abnormality test, bone marrow cell micronucleus test, and rat teratogenicity test), and chronic toxicity in mice were performed in this study. In the oral acute toxicity test, the LD50 in ICR mice was 481.99 mg/kg, with 95% confidence limits ranging from 404.27 to 574.70 mg/kg. All three mutagenicity tests tested negative in the range of 60.25–241.00 mg/kg. The results of the teratogenicity test in rats showed no reproductive or embryonic developmental toxicity at only 7.53 mg/kg, which can be considered as a no observed effect level (NOEL) for the teratogenicity test. Therefore, MPTA is safe for use at the doses tested, but attention should be paid to the potential risk to pregnant animals and the safety evaluation and toxicity mechanisms in target animals should be further investigated.

Evaluation of the cytotoxic, anticancer, and genotoxic activities of Acacia nilotica flowers and their effects on N-methyl-N-nitrosourea-induced genotoxicity in mice

PurposeIn this study, two main research objectives were examined: (1) the cytotoxic and anticancer activities of the aqueous methanol extract from Acacia nilotica flowers on three human cancer cells, namely lung A549, breast MCF-7, and leukemia THP-1 cells, and (2) the genotoxic effects of A. nilotica extract and its influence on DNA damage induced by N-methyl-N-nitrosourea (MNU) in mice.MethodsMice were orally treated with A. nilotica extract (200, 500, and 800 mg/kg for 4 days) with or without MNU (80 mg/kg intraperitoneally for 24 h).ResultsIn vitro experiments showed that A549 cells were the most sensitive to A. nilotica extract among the tested cell lines. A. nilotica extract inhibited A549 cell proliferation by blocking the cell cycle at the G2/M phase and accumulating apoptotic cells in the sub-G0/G1 phase in A549 cells. In vivo experiments showed that MNU induced positive and negative genotoxicity in bone marrow cells and spermatocytes, respectively. Negative genotoxicity was observed in A. nilotica extract-treated groups only. However, A. nilotica extract (800 mg/kg) remarkably increased comet tail formation in bone marrow cells. Unexpectedly, the absence of antigenotoxicity was observed in three cotreated groups with A. nilotica extract and MNU compared with the MNU-treated group. Astonishingly, cotreatment with MNU and A. nilotica extract at a dose above 200 mg/kg remarkably increased micronucleus and comet tail formation in bone marrow cells compared with the MNU-treated group.ConclusionsA. nilotica extract possessed anticancer activity with relative genotoxic effects at high doses.

Resveratrol-Tempeh reduce micronucleus frequencies bone marrow cells and stimulate osteocyte proliferation in aluminum chloride-induced mice.

Aluminum (Al) is widely used for water purification, cooking pots, cosmetic and pharmaceutical preparations, toothpaste tubes, and food processing industries. Although the transport in the digestive tract is very poor but if the load is high, it can be absorbed and accumulated. About 50-70% of Al accumulates in the bones and can have an impact on human health. Resveratrol (RES), isolated from tempeh as an Indonesian food ingredient, can increase cell viability and has promising cytoprotective effects. RES has the capacity to interact with oxidative stress, so it has the potential as a therapy in bone repair. Therefore, this study aimed to evaluate the effect of RES on the number of osteocytes and bone marrow cells in Al-induced mice. Swiss Webster mice were divided into four groups: (1) untreated groups, (2) AlCl3-treated groups, (3) Al+Res5 treated groups, and (4) Al+Res10 treated groups. Al dose 200 mg/kg body weight was administered intraperitoneally. RES was given one hour after administration of Al, with doses of 5 and 10 mg/kg Body Weight. Al and RES administration is carried out for one month. All mice were sacrificed, and mouse bones were isolated for histological preparations and a half for genotoxic assays. Bone marrow cells were collected and stained with My Grunwald. The number of micronuclei polychromatic erythrocytes (MNPCE) was examined in 1,000 PCEs per animal. The number of PCEs is counted by at least 200 erythrocytes (PCE + NCE) per animal. The results showed that the administration of Al significantly increased the number of micronuclei (MN) but after administration of RES at doses of 5 and 10 mg/kg Body Weight significantly reduced the number of MN in bone marrow cells. A dose of RES 10 mg/kg BW stimulates proliferation and increases the number of osteocytes in bone significantly. It can be concluded that Al can cause genotoxicity in bone marrow cells and RES is anti-genotoxic and can stimulate osteocyte proliferation.

Effect of dose and dose rate of gamma irradiation on the formation of micronuclei in bone marrow cells isolated from whole-body-irradiated mice.

It is well-known that the cytotoxicity and mutagenic effects of high dose rate (HDR) ionizing radiation (IR) are increased by increasing the dose but less is known about the effects of chronic low dose rate (LDR). In vitro, we have shown that in addition to the immediate interaction of IR with DNA (the direct and indirect effects), low doses and chronic LDR exposure induce endogenous oxidative stress. During elevated oxidative stress, reactive oxygen species (ROS) react with DNA modifying its structure. Here, BL6 mice were exposed to IR at LDR and HDR and were then sacrificed 3hours and 3 weeks after exposure to examine early and late effects of IR. The levels of micronuclei, MN, were determined in bone marrow cells. Our data indicate that the effects of 200 mGy on MN-induction are transient, but 500 and 1000 mGy (both HDR and LDR) lead to increased levels of MN up to 3 weeks after the exposure.

Detoxification gene expression, genotoxicity, and hepatorenal damage induced by subacute exposure to the new pyrethroid, imiprothrin, in rats.

The pyrethroid imiprothrin is widely used worldwide for control of insects in the agriculture and public health sectors. No sufficient information is however available concerning detoxification gene expression, i.e., cytochrome P450 1A2 (CYP1A2) and metallothionein 1a gene, oxidative stress, lipid peroxidation, DNA damage, cytotoxicity, genotoxicity, and organ injury induced by imiprothrin in mammals. This study is designed to explain the mechanism of imiprothrin induced detoxification gene expression, DNA damage, cytotoxicity, genotoxicity, and organ toxicity in male rats. The benchmark dose (BMD) was calculated to find the best sensitive markers to imiprothrin toxicity. Imiprothrin was injected intraperitoneally (i.p.) into male rats once a day for 5 days with doses of 19, 38, and 75 mg/kg body weight (b.wt.). Imiprothrin caused a significant increase in lipid peroxidation and changes in oxidative stress biomarkers in treated rats. Significant dose-dependent changes in the liver and kidney biomarkers were observed. Histopathological alterations were seen in the liver and kidney tissue of male rats. Imiprothrin also significantly increased chromosomal aberrations (CA) and micronuclei in bone-marrow cells, and induced lipid peroxidation, oxidative stress, cytotoxicity, and liver and kidney dysfunction, and damage. Imiprothrin induced DNA damage and over detoxification gene expression of CYP1A2 and metallothionein 1a gene in hepatocytes of male rats. Imiprothrin thus shows clastogenic and genotoxic potential. The mechanism for hepatorenal toxicity and injury, genotoxicity/cytotoxicity of imiprothrin might be due to enhanced lipid peroxidation, and oxidative stress associated with overproduction of free radicals, especially reactive oxygen species, and an imbalance in redox status. From the BMD models, aspartate aminotransferase (AST), total protein, uric acid, superoxide dismutase (SOD), and micronuclei (MPEs) were very sensitive markers to imiprothrin toxicity.

Network pharmacology reveals pharmacological effect and mechanism of Panax notoginseng (Burk.) F. H. Chen on reproductive and genetic toxicity in male mice

Ethnopharmacological relevanceCisplatin (CP), one of the most commonly used antitumor drugs in clinic, could induce reproductive and genetic toxicity. Traditional Chinese medicine believed that this side effect might be caused by the deficiency of both qi and blood. Panax notoginseng (Burk.) F. H. Chen (PN) is a traditional precious Chinese medicine for nourishing blood and hemostasis, which had the synergistic antitumor and reducing toxicity effects. However, the protective effect and mechanism of PN on CP-induced reproductive and genetic toxicity were still unknown.Aim of the study: This study was designed to illuminate the possible protective effect and mechanism of PN on CP-induced reproductive and genetic toxicity. Materials and methodsNetwork pharmacology was first applied to analyze the potential components and targets of PN against CP-induced reproductive and genetic toxicity. Then, the results of network pharmacology were validated in a mouse model of reproductive and genotoxicity induced by CP. Body weight, testis weight, epididymis weight, sperm count, sperm viability and sperm morphology were used to assess protective effects of PN on CP-induced reproductive toxicity. Tail moment in peripheral blood cells and micronucleus in bone marrow cells were used to assess protective effects of PN on CP-induced genetic toxicity. Finally, possible protective targets obtained from network pharmacology, including 8-hydroxy-2-deoxyguanosine (8-OHdG), malondialdehyde (MDA), total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px), were experimentally validated by ELISA. ResultsOne hundred and nineteen components of PN and sixty-eight targets of reproductive/genetic toxicity were acquired and constituted as the component-target network. Network pharmacology analysis showed alleviating oxidative stress might play important role in therapeutic mechanism of PN. In verified experiments, PN significantly improved the decline of body weight, testis weight and epididymis weight, increased sperm count and viability, decreased abnormal sperm morphology rate induced by CP in mice. Moreover, PN also significantly decreased the tail moment in peripheral blood cells and micronucleus formation rate in bone marrow cells in CP-induced mice. Finally, not only the decrease of T-SOD and GSH-Px level but also the increase of 8-OHdG and MDA level in serum were restored under PN treatment. ConclusionCurrent study found that PN could improve CP-induced reproductive and genetic toxicity, which were probably attributed to alleviating oxidative stress. This finding provided the new perspective for understanding the therapeutic effect of PN on CP-induced reproductive and genetic toxicity and facilitating the clinical use of PN.

Genotoxicity Evaluation of Capsaicin-Containing (CP) Pharmacopuncture, in an In Vivo Micronucleus Test.

ObjectivesCapsaicin-containing (CP) pharmacopuncture was developed to treat neuropathic pain. This study was conducted to assess the toxicity of CP extract for pharmacopuncture, using a micronucleus test.MethodsFirst, a dose range finding study was conducted. Then an in vivo micronucleus test was performed to determine the induction of micronuclei in mouse bone marrow cells after intramuscular administration of CP twice with a 24-hour interval to 8-week-old ICR mice. A high dose of 0.2 mL/animal was selected, and this was sequentially diluted by applying a geometric ratio of 2 to produce two lower dose levels (0.1 and 0.05 mL/animal). In addition, negative and positive control groups were set up, and an HPLC analysis was conducted to confirm the capsaicin content of CP.ResultsThe incidence of micro-nucleated polychromatic erythrocytes in polychromatic erythrocytes in the CP-treated group was similar to that in the negative-control group, while that in the positive-control group was significantly greater. In addition, the ratio of polychromatic erythrocytes to total erythrocytes in the CP treatment group and the positive control group was not significantly different from the negative control group. In the HPLC analysis, capsaicin in the CP was identified through a comparison with the retention time of the capsaicin standard of 27 min.ConclusionCP did not show any indication of any potential to induce micronuclei formation in bone marrow cells of ICR mice under the conditions of this study. Further toxicity studies are necessary to ensure the safety of the use of CP in clinical practice.

Effect of quinestrol on body weight, vital organs, biochemicals and genotoxicity in adult male lesser bandicoot rat, Bandicota bengalensis

The present study was aimed to evaluate the toxic effects of quinestrol (a synthetic estradiol) in male lesser bandicoot rat, Bandicota bengalensis. Effect was studied on body weight, weight of vital organs, changes in level of biochemical parameters and genotoxicity. Feeding of bait containing 0.01% quinestrol in bi-choice and 0.02 and 0.03% quinestrol in no-choice for a period of 10 days resulted in total ingestion of 19.50, 67.60 and 243.30 mg/kg bwt, respectively of the active ingredient. Autopsy of rats after 15 and 30 days of treatment withdrawal revealed no significant effect on body weight and weights of vital organs of rats. A significant decrease in the testicular levels of 17-beta hydroxysteroid dehydrogenase and increase in total soluble proteins was observed in rats treated with 0.02 and 0.03% quinestrol. The plasma levels of lipid peroxidation in the form of malondialdehyde concentration and lactate dehydrogenase increased significantly whereas the level of testosterone decreased significantly in treated rats. The plasma levels of acid and alkaline phosphatases, superoxide dismutase and total proteins differed non-significantly among rats of treated and untreated groups. The effect was found reversed partially in rats autopsied after 60 days of treatment withdrawal. No micronuclei in bone marrow cells, no aberrations in chromosomes and no DNA damage in blood cells during comet assay indicated no genotoxic effect of quinestrol on B. bengalensis at the test doses administered. The results thus revealed that quinestrol causes reversible toxic effects in the form of oxidative stress, increased lytic enzyme activity and decreased steroidogenesis which may further lead to testicular damage thereby inhibiting reproductive function. Also more effect was shown at higher doses ingested in no-choice test as compared to low doses ingested in bi-choice tests.

Acute and genetic toxicity of GS-E3D, a new pectin lyase-modified red ginseng extract

Korean red ginseng and its extract have been used as traditional medicines and functional foods in countries worldwide. Pectin lyase-modified red ginseng extract (GS-E3D) was newly developed as a dietary supplement for obesity, diabetes-related renal dysfunction, etc. In this study, the safety of GS-E3D on acute toxicity and genotoxicity was evaluated. For acute study, Sprague-Dawley rats were administrated by oral gavage at a dose of 5000 mg/kg GS-E3D. To evaluate genotoxicity of GS-E3D, we conducted three-battery tests, which are Ames test using Escherichia coli (WP2uvrA pKM101) and Salmonella typhimurium strains (TA98, TA100, TA1535 and TA1537), chromosomal aberration test -using Chinese hamster lung cells, and micronucleus test using ICR mice. In acute toxicity studies, there were no dead animals or abnormal necropsy findings in the control group and GS-E3D (5000 mg/kg) treated group. GS-E3D did not induce mutagenicity in the bacterial test, chromosomal aberrations in Chinese hamster lung cells and micronuclei in bone marrow cells of mice. Conclusively, the approximate lethal dose of GS-E3D was greater than 5000 mg/kg bw and GS-E3D has no genotoxic potential in the three-battery tests on genotoxicity.

Evaluation of antitumor activity and toxicity of Schinus terebinthifolia leaf extract and lectin (SteLL) in sarcoma 180-bearing mice

Ethnopharmacological relevanceSchinus terebinthifolia Raddi is a plant broadly used in folk medicine and the use of its leaf extract as an antitumor agent has been reported. Aim of the studyTo evaluate the antitumor potential and the toxicity of saline extract (SE) and lectin (SteLL) from S. terebinthifolia leaves in sarcoma 180-bearing mice. Materials and methodsCytotoxicity to sarcoma 180 cells was tested in vitro, and antitumor assay was performed using Swiss female mice. The treatments (0.15 M NaCl, negative control; methotrexate 1.5 mg/kg, positive control; SE 100 mg/kg; SteLL 1 and 5 mg/kg) by intraperitoneal injections started on the 8th day after tumor inoculation and lasted 7 days. It was analyzed: tumor weight; number and gauge of tumor vessels; hematological and biochemical parameters; histopathological changes; and occurrence of micronuclei in bone marrow cells. ResultsSE and SteLL showed IC50 values (concentrations that reduced cell viability to 50%) of 301.65 and 8.30 μg/mL, respectively. The lectin was able to induce apoptosis. Treatments with the extract and lectin caused a 57.6–73.6% reduction in tumor weight, which was not significantly different from the reduction in the methotrexate group. Tumors of animals treated with SteLL at 5 mg/kg showed reduced number of secondary vessels while the gauge was lower in all treated groups. In the groups treated with SteLL, tumors showed reduced and slightly vascularized parenchyma, with necrosis in the center and at the periphery. No alterations in the blood levels of urea, creatine, and glucose were detected while serum AST level was moderately increased in the SE group. Histopathological analysis revealed vacuolization and steatosis in the liver of animals treated with the extract and lectin. In addition, the treatments with SE and SteLL resulted in the reduction of filtration space and alterations in tubular architecture in kidneys. In respect to hematological parameters, it was only detected increase in the number of monocytes in SE group. The extract and lectin did not induce the formation of micronuclei in the bone marrow cells. ConclusionsSE and SteLL had antitumor effect against sarcoma 180 without inducing hematological changes and genotoxic effects in mice; however, some degree of hepatic and renal toxicity was observed, suggesting the evaluation of drug delivery strategies in the future.

Flaxseed oil as a protective agent against bisphenol-A deleterious effects in male mice

BackgroundFlaxseed oil is one of the most vital oils that contain a high content of omega-3 polyunsaturated fatty acids (PUFAs) recognized as a high-quality nutrition for health benefits. In addition, a source of vitamin E and β-carotene has a positive health effect in a variety of pathologies. The goal of the present work was to investigate the protecting character of flaxseed oil against bisphenol-A deleterious effects in male mice. Animals were gavaged with BPA for 28 successive days. They were orally administered flaxseed oil either before, with, or after treatment of BPA. DNA damage was evaluated in the liver, testes, and bone marrow cells using comet and micronucleus assays. Liver and testes histopathological examination as well as sperm physical characters were also investigated.ResultsThe results showed that BPA induced a significant raise in DNA damage that obviously appear in the increase of tail length, tail DNA percentage, and tail moment in the liver and testes. In addition, there was an increase in the frequency of micronuclei in bone marrow cells. Liver and testes histopathological alterations and sperm count and motility significant comedown were seen in male mice exposed to BPA as well. Conversely, flaxseed oil oral administration through the three regimens of treatment effectively attenuated the abovementioned effects. Moreover, administration of flaxseed oil before BPA treatment was the best protocol in the attenuation of BPA toxic effects.ConclusionsFlaxseed oil successfully attenuated the BPA genotoxicity, sperm defects, and histological alterations in male mice that may be referred to its antioxidant property.

Protective Effects on 60Co-γ Radiation Damage of Pine Cone Polyphenols from Pinus koraiensis-Loaded Chitosan Microspheres In Vivo.

A novel chitosan microsphere for encapsulating pine cone polyphenols (PP) from P. koraiensis was successfully prepared using an emulsion crosslinking technique. The characteristics of pine polyphenol-loaded microspheres (PPM) were determined using scanning electron microscopy (SEM) and a laser particle size detector. It was found that PPMs were spherical in shape with uniform particle size distribution patterns. The drug content and encapsulation rate of the microspheres were 7.47% and 73.6%, respectively, at a Ch/GA mass ratio of 0.7. The animal experiments showed that PPM had a stronger radiation protective effect than PP. PPM significantly increased the immune organ indices, the quantity of marrow DNA, the superoxide dismutase (SOD) activity, the splenocyte proliferation index, and the phagocytosis activity of monocytes. PPM also decreased the numbers of micronuclei in bone marrow cells and malondialdehyde (MDA) levels in plasma in mice exposed to 60Co γ-irradiation. In addition, gender differences in biological responses to exposure to radiation were observed.

Metformin prolongs survival rate in mice and causes increased excretion of cell-free DNA in the urine of X-irradiated rats

An antidiabetic drug metformin has anticarcinogenic and geroprotective effects and has been used in combination with radiation cancer therapy. The present work is devoted to the study of the effect of metformin on survival in mice, the frequency of micronuclei in mouse bone marrow cells and excretion of cell-free nuclear and mitochondrial DNA in the urine of X-ray-exposed rats. The survival rate and the frequency of micronuclei in mice and excretion of DNA into rat urine were determined after administration of the drug before and after irradiation of animals. The DNA content was measured by qRT-PCR. Metformin shows a radioprotective effect only when administered to mice after the radiation exposure. On the 11th day after irradiation, we observed 100% mortality in the control group; 78% of mice remained alive if metformin was given. Twenty percent of the mice in this group survived for 30 days after irradiation. Metformin has the same effect on the frequency of micronuclei; its reduction is observed, when the drug is administered to the mice after irradiation. Metformin promotes the excretion of nuclear and mitochondrial DNA with the urine of irradiated rats. The results show that metformin acts as a radiomitigation effector. Metformin promotes the active excretion of DNA of dying cells from the tissues of irradiated animals.

The adverse effects of bisphenol A on male albino rats

BackgroundBisphenol A (BPA) is a monomer used in the production of a multitude of chemical products, including epoxy resins and polycarbonates. The purpose of this study was to consider the biochemical, histological, genetic, and molecular alterations induced by BPA in adult male albino rats. They were orally subjected to BPA (20 and 100 mg/kg body weight) mixed in olive oil once a day for 30 days. At the end of the experiment, liver, testis, serum, and bone marrow were collected.ResultA significant increase in the level of malondialdehyde (MDA), with a significant decline in the content of superoxide dismutase (SOD) and reduced glutathione (GSH) in rats’ livers and testes after administration of both doses of BPA occurred. Also, there was a significant decrease in the testosterone activity in both treated groups. Histopathologic effects of bisphenol A on livers and testes of male rats showed that the treatment with both doses of BPA resulted in deleterious effects on livers and testes. The frequency of the micronucleus (MN) in polychromatic erythrocytes (PCEs) in bone marrow cells at both doses was significantly increased as compared to control group, while no changes were observed in polychromatic erythrocytes/normochromatic erythrocytes (PCEs/NCEs) ratio. Finally, BPA caused a suppressive effect on spermatogenesis-associated 7 (SPATA 7) gene in a dose-dependent manner.ConclusionExposure of rats to both selective doses of BPA leads to many adverse effects on liver and testis tissues. Also, an increase in frequency of the micronucleus in bone marrow cells was shown and suppression in the expression of SPATA 7 gene.

Radioprotective Effects of Sulfur-containing Mineral Water of Ramsar Hot Spring with High Natural Background Radiation on Mouse Bone Marrow Cells.

We intend to study the inhibitory effect of sulfur compound in Ramsar hot spring mineral on tumor-genesis ability of high natural background radiation. The radioprotective effect of sulfur compounds was previously shown on radiation-induced chromosomal aberration, micronuclei in mouse bone marrow cells and human peripheral lymphocyte. Ramsar is known for having the highest level of natural background radiation on Earth. This study was performed to show the radioprotective effect of sulfur-containing Ramsar mineral water on mouse bone marrow cells. Mice were fed three types of water (drinking water, Ramsar radioactive water containing sulfur and Ramsar radioactive water whose sulfur was removed). Ten days after feeding, mice were irradiated by gamma rays (0, 2 and 4 Gy). 48 and 72 hours after irradiating, mice were killed and femurs were removed. Frequency of micronuclei was determined in bone marrow erythrocytes. A significant reduction was shown in the rate of micronuclei polychromatic erythrocyte in sulfur-containing hot spring water compared to sulfur-free water in hot spring mineral water. Gamma irradiation induced significant increases in micronuclei polychromatic erythrocyte (MNPCE) and decreases in polychromatic erythrocyte/polychromatic erythrocyte + normochromatic erythrocyte ratio (PCEs/PCEs+NCEs) (P < 0.001) in sulfur-containing hot spring water compared to sulfur-free hot spring mineral water. Also, apparently there was a significant difference between drinking water and sulfur-containing hot spring water in micronuclei polychromatic erythrocyte and polychromatic erythrocyte/polychromatic erythrocyte+ normochromatic erythrocyte ratio. The results indicate that sulfur-containing mineral water could result in a significant reduction in radiation-induced micronuclei representing the radioprotective effect of sulfur compounds.

Analysis of different toxic impacts of Fipronil on growth, hemato-biochemistry, protoplasm and reproduction in adult cockerels

Fipronil (FIP), a broad-spectrum phenylpyrazole, is extensively used across the globe to control pests and as a veterinary drug. Incorrect use of FIP leads to contamination of soil and water ultimately causes toxic effects in non-target organisms. Therefore, the present experimental study was aimed to determine the deleterious effects of sub-lethal concentrations of FIP in adult cockerels. FIP mixed in corn oil was administered orally in different groups as follows: A = control, B = 1.5 mg/kg, C = 2.5 mg/kg, D = 3.5 mg/kg and E = 4.5 mg/kg body weight for 60 d. Signs of toxicity like anemic comb, tremors, gasping and watery droppings were evident in birds exposed to higher levels. The feed intake, body weight, absolute and the relative weight of different organs were significantly (p ≤ .05) decreased in birds exposed to higher concentrations. Histomorphometric analysis of small intestine in birds exposed to higher levels of FIP showed decreased villus height and crypt depth of duodenum, jejunum and ilium. Histologically, congestion in liver, pyknosis of hepatocytes and congestion in kidneys along with necrosis of tubular epithelial cells and increased urinary spaces were observed in birds. Microscopically, seminiferous tubules exhibited necrotic nuclei of the spermatids, arrest of process of spermatogenesis and admixture of necrotic cells in testes of exposed birds. Moreover, significantly (p ≤ .05) decreased hematological parameters such as erythrocytes counts, hemoglobin concentrations and hematocrit, while increased total leukocyte counts were recorded in birds. Furthermore, significantly (p ≤ .05) increased concentrations of serum urea, creatinine, alanine aminotransferase, aspartate aminotransferase and cardiac isoenzyme (CK-MB), while reduced serum testosterone levels were recorded in birds. Results revealed significantly (p ≤ .05) increased frequency of micronuclei in erythrocyte and bone marrow cells. The findings of our study demonstrated that FIP induces deleterious impacts on multiple tissues in birds even at low doses.

Toxicology evaluation of selenium protein powder

The experiment was conducted to evaluate the safety of selenium protein powder, a novel organic selenium nutritional supplement, and reported corresponding data and results based on a series of toxicological tests. It was examined to evaluate oral acute toxicity by median lethal dose test and mutagenic potential by bone marrow cell micronucleus test and sperm abnormality test using Kun-Ming mice. The results showed that the oral LD 50 of selenium protein powder exceeded 31.25 g/kg body weight in mice. No mutagenicity was found by mouse bone marrow cell micronucleus test and mouse sperm abnormality test. The results suggested greater safety of selenium protein powder as a nutritional selenium supplement, and selenium protein powder has the potential for development and application in food systems or functional foods.

Intracellularly Swollen Polypeptide Nanogel Assists Hepatoma Chemotherapy.

Nowadays, chemotherapy is one of the principal modes of treatment for tumor patients. However, the traditional formulations of small molecule drugs show short circulation time, low tumor selectivity, and high toxicity to normal tissues. To address these problems, a facilely prepared, and pH and reduction dual-responsive polypeptide nanogel was prepared for selectively intracellular delivery of chemotherapy drug. As a model drug, doxorubicin (DOX) was loaded into the nanogel through a sequential dispersion and dialysis technique, resulting in a high drug loading efficiency (DLE) of 96.7 wt.%. The loading nanogel, defined as NG/DOX, exhibited a uniform spherical morphology with a mean hydrodynamic radius of 58.8 nm, pH and reduction dual-triggered DOX release, efficient cell uptake, and cell proliferation inhibition in vitro. Moreover, NG/DOX exhibited improved antitumor efficacy toward H22 hepatoma-bearing BALB/c mouse model compared with free DOX·HCl. Histopathological and immunohistochemical analyses were implemented to further confirm the tumor suppression activity of NG/DOX. Furthermore, the variations of body weight, histopathological morphology, bone marrow cell micronucleus rate, and white blood cell count verified that NG/DOX showed excellent safety in vivo. With these excellent properties in vitro and in vivo, the pH and reduction dual-responsive polypeptide nanogel exhibits great potential for on-demand intracellular delivery of antitumor drug, and holds good prospect for future clinical application.