Browsing by Author "Mohamed, Hanan R. H"

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Alleviation of calcium hydroxide nanoparticles induced genotoxicity and gastritis by coadministration of calcium titanate and yttrium oxide nanoparticles in mice
(Nature Publishing Group, 2023-11) Mohamed, Hanan R. H; Elbasiouni, Salma H; Farouk, Ahmed H; Nasif, KirollsA; Nasraldin, Karima; Safwat, Gehan
Diverse applications of nanoparticles due to their unique properties has rapidly increased human exposure to numerous nanoparticles such as calcium hydroxide (Ca(OH)2), calcium titanate (CaTiO3), and yttrium oxide (Y2O3) nanoparticles almost in all aspect of daily life. However, very limited data are available on the efect of these nanoparticles on genomic DNA integrity and infammation induction in the gastric tissues. Hence, this study estimated the efect of Ca(OH)2, CaTiO3, or/and Y2O3 nanoparticles multiple oral administration on the genomic DNA damage and infammation induction in the mice gastric tissues. A suspension containing 50 mg/kg b.w of Ca(OH)2, CaTiO3, or Y2O3 nanoparticles were given orally to male mice separately or together simultaneously three times a week for two consecutive weeks. Multiple oral administration of Ca(OH)2 nanoparticles led to signifcant elevations in DNA damage induction and ROS generation, in contrast to the non-signifcant changes observed in the level of induced DNA damage and generated ROS after administration of CaTiO3 or Y2O3 nanoparticles separately or in combination with Ca(OH)2 nanoparticles. Oral administration of Ca(OH)2 nanoparticles alone also highly upregulated INOS and COX-2 genes expression and extremely decreased eNOS gene expression. However, high elevations in eNOS gene expression were detected after multiple administration of CaTiO3 and Y2O3 nanoparticles separately or together simultaneously with Ca(OH)2 nanoparticles. Meanwhile, non-remarkable changes were noticed in the expression level of INOS and COX-2 genes after administration of CaTiO3 and Y2O3 nanoparticles separately or simultaneously together with Ca(OH)2 nanoparticles. In conclusion: genomic DNA damage and infammation induced by administration of Ca(OH)2 nanoparticles alone at a dose of 50 mg/kg were mitigated by about 100% when CaTiO3 and Y2O3 nanoparticles were coadministered with Ca(OH)2 nanoparticles until they reached the negative control level through altering the expression level of eNOS, INOS and COX-2 genes and scavenging gastric ROS. Therefore, further studies are recommended to investigate the toxicological properties of Ca(OH)2, CaTiO3 and Y2O3 nanoparticles and possibility of using CaTiO3 and Y2O3 nanoparticles to mitigate genotoxicity and infammation induction by Ca(OH)2 nanoparticles.
Alleviation of calcium hydroxide nanoparticles induced genotoxicity and gastritis by coadministration of calcium titanate and yttrium oxide nanoparticles in mice
(Nature Publishing Group, 2023-12) Mohamed, Hanan R. H; Elbasiouni, Salma H; Farouk, Ahmed H; Nasif, KirollsA; Nasraldin, Karima; Safwat, Gehan
Diverse applications of nanoparticles due to their unique properties has rapidly increased human exposure to numerous nanoparticles such as calcium hydroxide (Ca(OH)2), calcium titanate (CaTiO3), and yttrium oxide (Y2O3) nanoparticles almost in all aspect of daily life. However, very limited data are available on the effect of these nanoparticles on genomic DNA integrity and inflammation induction in the gastric tissues. Hence, this study estimated the effect of Ca(OH)2, CaTiO3, or/and Y2O3 nanoparticles multiple oral administration on the genomic DNA damage and inflammation induction in the mice gastric tissues. A suspension containing 50 mg/kg b.w of Ca(OH)2, CaTiO3, or Y2O3 nanoparticles were given orally to male mice separately or together simultaneously three times a week for two consecutive weeks. Multiple oral administration of Ca(OH)2 nanoparticles led to significant elevations in DNA damage induction and ROS generation, in contrast to the non-significant changes observed in the level of induced DNA damage and generated ROS after administration of CaTiO3 or Y2O3 nanoparticles separately or in combination with Ca(OH)2 nanoparticles. Oral administration of Ca(OH)2 nanoparticles alone also highly upregulated INOS and COX-2 genes expression and extremely decreased eNOS gene expression. However, high elevations in eNOS gene expression were detected after multiple administration of CaTiO3 and Y2O3 nanoparticles separately or together simultaneously with Ca(OH)2 nanoparticles. Meanwhile, non-remarkable changes were noticed in the expression level of INOS and COX-2 genes after administration of CaTiO3 and Y2O3 nanoparticles separately or simultaneously together with Ca(OH)2 nanoparticles. In conclusion: genomic DNA damage and inflammation induced by administration of Ca(OH)2 nanoparticles alone at a dose of 50 mg/kg were mitigated by about 100% when CaTiO3 and Y2O3 nanoparticles were coadministered with Ca(OH)2 nanoparticles until they reached the negative control level through altering the expression level of eNOS, INOS and COX-2 genes and scavenging gastric ROS. Therefore, further studies are recommended to investigate the toxicological properties of Ca(OH)2, CaTiO3 and Y2O3 nanoparticles and possibility of using CaTiO3 and Y2O3 nanoparticles to mitigate genotoxicity and inflammation induction by Ca(OH)2 nanoparticles.
Estimation of genomic and mitochondrial DNA integrity in the renal tissue of mice administered with acrylamide and titanium dioxide nanoparticles
(Nature Publishing Group, 2023-08) Mohamed, Hanan R. H; Behira, Loren S.T; Diab, Ayman
The Kidneys remove toxins from the blood and move waste products into the urine. However, the accumulation of toxins and fuids in the body leads to kidney failure. For example, the overuse of acrylamide and titanium dioxide nanoparticles (TiO2NPs) in many food and consumer products increases human exposure and risks; however, there are almost no studies available on the efect of TiO2NPs coadministration with acrylamide on the integrity of genomic and mitochondrial DNA. Accordingly, this study was conducted to estimate the integrity of genomic and mitochondrial DNA in the renal tissue of mice given acrylamide and TiO2NPs. To achieve this goal, mice were administrated orally TiO2NPs or/and acrylamide at the exposure dose levels (5 mg/kg b.w) and (3 mg/ kg b.w), respectively, fve times per week for two consecutive weeks. Concurrent oral administration of TiO2NPs with acrylamide caused remarkable elevations in the tail length, %DNA in tail and tail moment with higher fragmentation incidence of genomic DNA compared to those detected in the renal tissue of mice given TiO2NPs alone. Simultaneous coadministration of TiO2NPs with acrylamide also caused markedly high elevations in the reactive oxygen species (ROS) production and p53 expression level along with a loss of mitochondrial membrane potential and high decreases in the number of mitochondrial DNA copies and expression level of β catenin gene. Therefore, from these fndings, we concluded that concurrent coadministration of acrylamide with TiO2NPs augmented TiO2NPs induced genomic DNA damage and mitochondrial dysfunction through increasing intracellular ROS generation, decreasing mitochondrial DNA Copy, loss of mitochondrial membrane potential and altered p53 and β catenin genes expression. Therefore, further studies are recommended to understand the biological and toxic efects resulting from TiO2NPs with acrylamide coadministration.
Estimation of genotoxicity, apoptosis and oxidative stress induction by TiO2 nanoparticles and acrylamide subacute oral coadministration in mice
(2022-11) Safwat, Gehan; Mohamed, Amira A; Mohamed, Hanan R. H
Acrylamide is used in the industry and can be a by-product of high-temperature food processing which has toxic potential in various tissues, and titanium dioxide nanoparticles (TiO2NPs) are widely used in toothpaste, sweets, food perseveration, chewing gum and medicines. Consequently, humans are daily exposed to large amounts of acrylamide and TiO2NPs mainly through food intake. However, limited studies are available on the efect of simultaneously intake of acrylamide and TiO2NPs on the integrity of genomic DNA and the induction of apoptosis in brain tissues. Therefore, this study estimated the infuence of acrylamide coadministration on TiO2NPs induced genomic instability and oxidative stress in the brain tissues of mice. To achieve this, mice were orally administrated acrylamide (3 mg/kg b.w) or/and TiO2NPs (5 mg/kg b.w) for two successive weeks (5 days per week). The comet assay results showed that concurrent oral administration of acrylamide and TiO2NPs strongly induced single- and double stranded DNA breaks, and that the level of reactive oxygen species (ROS) was also highly elevated within neural cells after simultaneous oral intake of acrylamide and TiO2NPs compared to those observed after administration of acrylamide or/TiO2NPs alone. Moreover, oral co-administration of acrylamide with TiO2NPs increased apoptotic DNA damage to neurons by upregulating the expression levels of P53, TNF-α, IL-6 and Presenillin-1 genes compared to groups administered TiO2NPs. Therefore, from these results, the present study concluded that coadministration of acrylamide renders TiO2NPs more genotoxic and motivates apoptotic DNA damage and oxidative stress induced by TiO2NPs in brain cells, and thus it is recommended to avoid concurrent oral acrylamide administration with TiO2NPs.
Genotoxicity and oxidative stress induction by calcium hydroxide, calcium titanate or/and yttrium oxide nanoparticles in mice
(Nature Publishing Group, 2023-11) Mohamed, Hanan R. H; Farouk, Ahmed H; Elbasiouni, Salma H; Nasif, Kirolls A; Safwat, Gehan; Diab, Ayman
Intensive uses of Calcium hydroxide (Ca(OH)2NPs), calcium titanate (CaTiO3NPs) and yttrium oxide (Y2O3NPs) nanoparticles increase their environmental release and human exposure separately or together through contaminated air, water and food. However, too limited data are available on their genotoxicity. Therefore, this study explored the efect of Ca(OH)2NPs, CaTiO3NPs or/and Y2O3NPs administration on the genotoxicityand oxidative stress induction in mice hepatic tissue. Mice were orally administered Ca(OH)2NPs, CaTiO3NPs and Y2O3NPs separately or simultaneously together at a dose level of 50 mg/kg b.w. for two successive weeks (3 days per week). Marked induction of DNA damage noticed after oral administration of Ca(OH)2NPs or CaTiO3NPs alone together with high Ca(OH)2NPs induced reactive oxygen species (ROS) generation and a slight CaTiO3NPs induced ROS production were highly decreased after simultaneous coadministration of administration of Y2O3NPs with Ca(OH)2NPs and CaTiO3NPs up to the negative control level. Oral administration of Y2O3NPs alone also did not cause observable changes in the genomic DNA integrity and the ROS generation level compared to the negative control levels. Similarly, signifcant elevations in P53 gene expression and high reductions in Kras and HSP-70 genes expression were observed only after administration of Ca(OH)2NPs alone, while, remarkable increases in the Kras and HSP-70 genes expression and non-signifcant changes in p53 gene expression were noticed after administration of CaTiO3NPs and Y2O3NPs separately or simultaneously together with Ca(OH)2NPs. Conclusion: Ca(OH)2NPs exhibited the highest genotoxic efect through oxidative stress induction and disruption of apoptotic (p53 and Kras) and protective (HSP-70) genes expression. Slight DNA damage was noticed after CaTiO3NPs administration. However, administration of Y2O3NPs alone was non-genotoxic and coadministration of Y2O3NPs with Ca(OH)2NPs and CaTiO3NPs restored genomic DNA integrity and normal expression of apoptotic p53 and protective HSP-70 genes disrupted by Ca(OH)2NPs and CaTiO3NPs. Thus co-administration of Y2O3NPs with Ca(OH)2NPs and CaTiO3NPs is recommended to counter Ca(OH)2NPs and CaTiO3NPs induced genotoxicity and oxidative stress.
Induction of oxidative DNA damage, cell cycle arrest and p53 mediated apoptosis by calcium titanate nanoparticles in MCF-7 breast cancer cells
(BioMed Central Ltd., 2022-11) Mohamed, Hanan R. H; Ibrahim, Maria M. H; Diab, Ayman
Background: The distinctive properties and high activity of calcium titanate nanoparticles (CaTiO3-NPs) increase their use in many products. However, the cytotoxic and genotoxic efects of CaTiO3-NPs in human cancer cell lines have not been well studied. Therefore, this study was conducted to explore CaTiO3-NPs induced cytotoxicity, genomic instability and apoptosis in human breast cancer (MCF-7) cells. Methods: Sulforhodamine B (SRB) and the alkaline comet assays were done to study cell viability and DNA damage induction, respectively. Apoptosis induction and cell cycle distribution were analyzed using fow cytometry. The level of intracellular reactive oxygen species (ROS) was studied, and the expression levels of p53, Bax and Bcl2 genes were also measured. Results: The results of the Sulforhodamine B (SRB) cytotoxicity assay showed that viability of MCF-7 cells was not afected by CaTiO3-NPs treatment for 24 h, however, exposure to CaTiO3-NPs for 72 h caused concentrations depend- ent death of MCF-7 cells. Treatment with CaTiO3-NPs for 72 h caused marked increases in intracellular ROS level and induced DNA damage. Treatment of MCF-7 cells with CaTiO3-NPs also caused MCF-7 cell cycle arrest at the G0 and S phases and s triggered apoptosis of MCF-7 cells by causing simultaneous increases in the expression levels of apop- totic p53 and Bax genes and a decrease in the expression level of anti-apoptotic Bcl2 gene. Conclusion: Collectively, it was concluded that CaTiO3-NPs cause time- and concentration-dependent cytotoxic efects in human MCF-7 cells through induction of ROS generation, genomic instability and apoptosis. Thus it is recommended that further in vitro and in vivo studies are therefore recommended to understand the cytotoxic and biological efects of CaTiO3-NPs.
Induction of ROS mediated genomic instability, apoptosis andG0/G1 cell cycle arrest by erbium oxide nanoparticles in human hepatic Hep‑G2 cancer cells
(2022-09) Safwat, Gehan; Soliman, Esraa S. M; Mohamed, Hanan R. H
The remarkable physical and chemical characteristics of noble metal nanoparticles, such as high surface-to-volume ratio, broad optical properties, ease of assembly, surfactant and functional chemistry, have increased scientifc interest in using erbium oxide nanoparticles (Er2O3-NPs) and other noble metal nanostructures in cancer treatment. However, the therapeutic efect of Er2O3-NPs on hepatic cancer cells has not been studied. Therefore, the current study was conducted to estimate the therapeutic potential of Er2O3-NPs on human hepatocellular carcinoma (Hep-G2) cells. Exposure to Er2O3-NPs for 72 h inhibited growth and caused death of Hep-G2 cells in a concentration dependent manner. High DNA damage and extra-production of intracellular reactive oxygen species (ROS) were induced by Er2O3-NPs in Hep-G2 cells. As determined by fow cytometry, Er2O3-NPs arrested Hep-G2 cell cycle at the G0/G1 phase and markedly increased the number of Hep-G2 cells in the apoptotic and necrotic phases. Moreover, Er2O3-NPs caused simultaneous marked increases in expression levels of apoptotic (p53 and Bax) genes and decreased level of anti-apoptotic Bcl2 gene expression level in Hep- G2 cells. Thus it is concluded that Er2O3-NPs inhibit proliferation and trigger apoptosis of Hep-G2 cells through the extra ROS generation causing high DNA damage induction and alterations of apoptotic genes. Thus it is recommended that further in vitro and in vivo studies be carried out to study the possibility of using Er2O3-NPs in the treatment of cancer.
Modulation efciency of clove oil nano‑emulsion against genotoxic, oxidative stress, and histological injuries induced via titanium dioxide nanoparticles in mice
(Nature Publishing Group, 2024-12) Mohamed, Hanan R. H; El‑Shamy, Sawsan; Abdelgayed, Sherein S; Albash, Rofda; El‑Shorbagy, Haidan
Titanium dioxide nanoparticles (TiO2-NPs) have found wide applications in medical and industrial felds. However, the toxic efect of various tissues is still under study. In this study, we evaluated the toxic efect of TiO2-NP on stomach, liver, and kidney tissues and the amelioration efect of clove oil nanoemulsion (CLV-NE) against DNA damage, oxidative stress, pathological changes, and the apoptotic efect of TiO2-NPs. Four groups of male mice were subjected to oral treatment for fve consecutive days including, the control group, the group treated with TiO2-NPs (50 mg/kg), the group treated with (CLV-NE) (5% of the MTD), and the group treated with TiO2-NPs plus CLV-NE. The results revealed that the treatment with TiO2-NPs signifcantly caused DNA damage in the liver, stomach, and kidney tissues due to increased ROS as indicated by the reduction of the antioxidant activity of SOD and Gpx and increased MDA level. Further, abnormal histological signs and apoptotic efect confrmed by the signifcant elevation of p53 expression were reported after TiO2-NPs administration. The present data reported a signifcant improvement in the previous parameters after treatment with CLV-NE. These results showed the collaborative efect of the oils and the extra role of nanoemulsion in enhancing antioxidant efectiveness that enhances its disperse-ability and further promotes its controlled release. One could conclude that CLV-NE is safe and can be used as a powerful antioxidative agent to assess the toxic efects of the acute use of TiO2-NPs.
Yttrium oxide nanoparticles ameliorates calcium hydroxide and calcium titanate nanoparticles induced genomic DNA and mitochondrial damage, ROS generation and infammation
(Nature Publishing Group, 2024-06) Mohamed, Hanan R. H; Farouk, Ahmed H; Elbasiouni, Salma H; Nasif, Kirolls A; Safwat, Gehan
Calcium hydroxide (Ca(OH)2NPs), calcium titanate (CaTiO3NPs) and yttrium oxide (Y2O3NPs) nanoparticles are prevalent in many industries, including food and medicine, but their small size raises concerns about potential cellular damage and genotoxic efects. However, there are very limited studies available on their genotoxic efects. Hence, this was done to investigate the efects of multiple administration of Ca(OH)2NPs, CaTiO3NPs or/and Y2O3NPs on genomic DNA stability, mitochondrial membrane potential integrity and infammation induction in mouse brain tissues. Mice were orally administered Ca(OH)2NPs, CaTiO3NPs or/and Y2O3NPs at a dose level of 50 mg/kg b.w three times a week for 2 weeks. Genomic DNA integrity was studied using Comet assay and the level of reactive oxygen species (ROS) within brain cells was analyzed using 2,7 dichlorofuorescein diacetate dye. The expression level of Presenilin-1, tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6) genes and the integrity of the mitochondrial membrane potential were also detected. Oral administration of Ca(OH)2NPs caused the highest damage to genomic DNA and mitochondrial membrane potential, less genomic DNA and mitochondrial damage was induced by CaTiO3NPs administration while administration of Y2O3NPs did not cause any remarkable change in the integrity of genomic DNA and mitochondrial membrane potential. Highest ROS generation and upregulation of presenilin-1, TNF-α and IL-6 genes were also observed within the brain cells of mice administrated Ca(OH)2NPs but Y2O3NPs administration almost caused no changes in ROS generation and genes expression compared to the negative control. Administration of CaTiO3NPs alone slightly increased ROS generation and the expression level of TNF-α and IL-6 genes. Moreover, no remarkable changes in the integrity of genomic DNA and mitochondrial DNA potential, ROS level and the expression level of presenilin-1, TNF-α and IL-6 genes were noticed after simultaneous coadministration of Y2O3NPs with Ca(OH)2NPs and CaTiO3NPs. Coadministration of Y2O3NPs with Ca(OH)2NPs and CaTiO3NPs mitigated Ca(OH)2NPs and CaTiO3NPs induced ROS generation, genomic DNA damage and infammation along with restoring the integrity of mitochondrial membrane potential through Y2O3NPs scavenging free radicals ability. Therefore, further studies are recommended to study the possibility of using Y2O3NPs to alleviate Ca(OH)2NPs and CaTiO3NPs induced genotoxic efects.