Hanan R. H. Mohamed

Estimation of TiO2 nanoparticle-induced genotoxicity persistence and possible chronic gastritis-induction in mice

Titanium dioxide (TiO2) nanoparticles are widely used as a food additive and coloring agent in many consumer products however limited data is available on the nano-TiO2 induced genotoxicity persistence. Thus, this study investigated the persistence of nano-TiO2 induced genotoxicity and possible induction of chronic gastritis in mice. The mice were orally administered 5, 50 or 500 mg/kg body weight nano-TiO2 for five consecutive days, and then mice from each dosage group were sacrificed 24 h or one or two weeks after the last treatment. The administration of nano-TiO2 resulted in persistent apoptotic DNA fragmentation and mutations in p53 exons (5-8) as well as significant persistent elevations in malondialdehyde and nitric oxide levels and decreases in the reduced glutathione level and catalase activity compared with the control mice in a dose- and time-dependent manner. Necrosis and inflammation were evident upon histological examination. These findings could be attributed to the persistent accumulation of nano-TiO2 at the tested doses at all three time points. Based on these findings, we conclude that the administration of nano-TiO2, even at low doses, leads to persistent accumulation of nano-TiO2 in mice, resulting in persistent inflammation, apoptosis and oxidative stress, ultimately leading to the induction of chronic gastritis.

Normalization of Nano-Sized TiO2-Induced Clastogenicity, Genotoxicity and Mutagenicity by Chlorophyllin Administration in Mice Brain, Liver, and Bone Marrow Cells

The intensive uses of titanium dioxide (TiO2) nanoparticles in sunscreens, toothpaste, sweats, medications, etc. making humans exposed to it daily by not little amounts and also increased its risks including genotoxicity. Thus, the present study was designed as one way to reduce nano-titanium-induced clastogenicity, genotoxicity, and mutagenicity in mice by co-administration of the free radical scavenger chlorophyllin (CHL). In addition, markers of oxidative stress were detected to shed more light on mechanism(s) underlying nano-sized TiO2 genotoxicity. Male mice were exposed to multiple injection into the abdominal cavity for five consecutive days with either CHL (40 mg/kg bw/day), or each of three dose levels of nano-sized TiO2 (500, 1000, or 2000 mg/kg bw/day) alone, or both simultaneously and sacrificed by cervical dislocation 24 h after the last treatment. After CHL co-administration, the observed dose-dependent genotoxicity of TiO2 nanoparticles indicated by the significant elevations in frequencies of both micronuclei and DNA damage induction was significantly decreased and returned to the negative control level. The observed induced mutations in p53 exons 5, 7, & 8 and 5 & 8 in the liver and brain, respectively, were declined in most cases. Moreover, CHL significantly decreased hepatic malondialdehyde level and significantly increased glutathione level and superoxide dismutase, catalase, and glutathione peroxidase activities that were significantly disrupted in animal groups treated with nano-TiO2 alone. In conclusion, the evidenced in vivo genotoxicity of nano-TiO2 in the present study was normalized after CHL co-administration which supports the previously suggested oxidative stress as the possible mechanism for titanium toxicity.

Studies on the Genotoxicity Behavior of Silver Nanoparticles in the Presence of Heavy Metal Cadmium Chloride in Mice

Incredible rapid growth in the nanoparticles applications and development increases the daily human exposure to them but humans are exposed to many other pollutants in addition to nanoparticles that forced us to evaluate the effect of heavy metal cadmium chloride (CdCl2) coinjection on silver nanoparticles induced genotoxic risk in this study. Mice were injected into the abdominal cavity with single dose of Ag nanoparticles (20, 41, and 82 mg/kg) or CdCl2 (1.5 mg/kg) either separately or together simultaneously and sacrificed 24 hours later. CdCl2 cotreatment enhanced the induced dose-dependent sperm abnormality by Ag nanoparticles different doses as shown by the statistical significant decreases in both sperm concentration and motility and increases in the frequency of abnormal sperms and also potentiated the Ag nanoparticles induced chromosomal and DNA damage indicated by the statistical significant elevations in the frequencies of micronucleated polychromatic erythrocytes (MNPCEs) and DNA damage levels. Moreover, statistical elevations in malondialdehyde level and reductions in catalase activity were observed after CdCl2 coinjection with Ag nanoparticles compared with Ag nanoparticles treated groupsź values. Ag nanoparticles induced sperm abnormality, clastogenicity, and genotoxicity were potentiated by heavy metal cadmium coinjection that threatens the human life and increases silver nanoparticles genotoxic risks.

Amelioration of ethanol induced apoptotic DNA damage and ulcerative injuries in the mice gastric tissues by starch oral administration

Abstract Nowadays, gastric ulcers have become very common gastrointestinal disorders and numerous natural plant extracts exert promising anti-ulcerative effects. Therefore, this study was designed to evaluate the possible protective effect of dietary starch against ethanol induced gastric ulcers in mice. Post-administration of dietary starch for three consecutive days caused remarkable ameliorations in hemorrhagic lesions in gastric mucus and significant suppression in % incidence of ulceration, ulcer index and ulcer score induced by ethanol single administration. Indeed, deep ulceration, necrosis, disruption and degeneration in large areas of mucosa layer together with dense inflammatory cells infiltration and edema in sub-mucosal layer induced by ethanol administration were attenuated by starch post-administration and normalized the tissue architecture of the stomach. This potential protective effect could be attributed to the potent anti-oxidative capacity of starch that causes scavenger of the reactive oxygen species and thereby decreasing single and double DNA stranded break inductions and apoptotic DNA damage revealed by returning the p53 and caspase-3 expression levels to the normal level compared to the ethanol treated group. In conclusion, dietary starch has a potent therapeutic effect against ethanol induced gastric ulcer in mice via its free radical scavengers ability. Thus, we recommended further studies on its possible use as antiulcer drugs.

Genotoxicity Studies of Titanium Dioxide Nanoparticles (TiO2NPs) in the Brain of Mice.

Titanium dioxide nanoparticles (TiO2NPs) are excessively used and represent one of the top five most commonly used nanoparticles worldwide. Recently, various studies referred to their toxic potential on various organs using different treatment route. Male Swiss Webster mice were orally administrated TiO2NPs (500 mg/kg b.w.) daily for five consecutive days and then animals were sacrificed at 24 h, 7 days, or 14 days after the last treatment. The present results report that exposure to TiO2NPs produces mild to moderate changes in the cytoarchitecture of brain tissue in a time dependent manner. Moreover, Comet assay revealed the apoptotic DNA fragmentation, while PCR-SSCP pattern and direct sequencing showed point mutation of Presenilin 1 gene at exon 5, gene linked to inherited forms of the Alzheimers disease. Therefore, from these findings, the present study concluded that TiO2NPs is genotoxic and mutagenic to brain tissue which in turn might lead to Alzheimers disease incidence.

Amelioration of cobalt oxide nanoparticles induced genomic and mitochondrial DNA damage and oxidative stress by omega-3 co-administration in mice

ABSTRACT Increased human exposure to cobalt oxide nanoparticles (CoO-NPs) because of their widespread use in many industrial and medical applications makes the study of genotoxicity and mutagenicity necessary. Therefore, this study was conducted to assess the genomic and mitochondrial DNA damage induction by CoO-NPs and the possible protective role of omega-3 in mice. The simultaneous administration of omega-3 significantly reduced DNA damage caused by CoO-NPs, which was evaluated by restoring the normal intact appearance of genomic DNA running on the agarose gel and normalizing fractionated DNA. The elevated malondialdehye (MDA) level and the reduced catalase (CAT) and glutathione peroxidase (Gpx) activities by CoO-NPs oral administration were normalized by omega-3 co-administration. Moreover, the omega-3 co-administration reduced the incidence of mutations induced by CoO-NPs in mitochondrial D-loop from 67% to 33%. We concluded that genomic and mitochondrial DNA damage and oxidative stress caused by CoO-NPs was mitigated by omega-3 co-administration.

Estimating the modulatory effect of cadmium chloride on the genotoxicity and mutagenicity of silver nanoparticles in mice

Silver (Ag) nanoparticles (nano-Ag) are widely used because of their distinctive antimicrobial properties, but this widespread use increases Ag release into the environment along with many other pollutants such as heavy metals. Therefore, this study was undertaken to study the modulatory effect of cadmium chloride (CdCl2) on the genotoxicity and mutagenicity of nano-Ag in mice liver, kidney and brain tissues. Co-injections of CdCl2 (1.5 mg/kg) with nano-Ag (20, 41, or 82 mg/kg) resulted in significant elevations in both single and double DNA strand breaks that triggered higher apoptotic DNA damage, as revealed by the more fragmented appearance of genomic DNA and the significant increase in apoptotic fractions. Concurrent higher mutation incidence in the presenilin-1 and p53 genes was observed after CdCl2 co-treatment than in nano-Ag-treated groups. Immuno-histochemical localization of p53 protein revealed the overexpression of the p53 gene and the histological examination showed diffusely degenerated, congested blood vessels and the infiltration of leukocytes in the liver, kidney, and brain tissues of the groups co-treated with nano-Ag and CdCl2. Moreover, CdCl2 co-injection with nano-Ag increased reactive oxygen species (ROS) generation, as revealed by increased malondialdehyde levels, decreased glutathione levels, and decreased superoxide dismutase and glutathione peroxidase activity, compared with those induced by nano-Ag particles alone. We concluded that CdCl2 enhanced the nano-Ag-induced genotoxicity via increasing mutation incidence in p53 and presenilin-1 gene.

Nullification of aspirin induced gastrotoxicity and hepatotoxicity by prior administration of wheat germ oil in Mus musculus: histopathological, ultrastructural and molecular studies

Aspirin (acetyl salicylic acid) is used worldwide to treat various inflammatory conditions and prevent cardiovascular disease, along with reducing the risk of cancer. However, administration of aspirin causes toxic effects, especially in the stomach and liver. Thus, our study examined the protective effect of wheat germ oil on aspirin-induced toxicity in the stomach and liver tissues of Swiss albino mice. Administration of wheat germ oil before aspirin has restored normal hepatic and gastric tissue architecture and DNA integrity has become better than that of a negative health control group compared with the aspirin only treated group. The elevated gastric nitric oxide content in the aspirin only treated group was significantly decreased by wheat germ oil prior administration as a result of reduced the expression of inducible nitric synthase and increased the expression of endothelial nitric oxide synthase compared to their expression in the aspirin administered group. Wheat germ oil pre-administration significantly reduced the level of malondialdehyde, increased the level of glutathione and catalase and superoxide dismutase activities compared with those in aspirin only treated group. We conclude that wheat germ oil has a potential protective effect against aspirin induced gastro- and hepato-toxicity because of its free radical scavenging ability.