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Calcium hydroxide (Ca(OH) 2 NPs), calcium titanate (CaTiO 3 NPs) and yttrium oxide (Y 2 O 3 NPs) nanoparticles are prevalent in many industries, including food and medicine, but their small size raises concerns about potential cellular damage and genotoxic effects. However, there are very limited studies available on their genotoxic effects. Hence, this was done to investigate the effects of multiple administration of Ca(OH) 2 NPs, CaTiO 3 NPs or/and Y 2 O 3 NPs on genomic DNA stability, mitochondrial membrane potential integrity and inflammation induction in mouse brain tissues. Mice were orally administered Ca(OH) 2 NPs, CaTiO 3 NPs or/and Y 2 O 3 NPs 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 dichlorofluorescein 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) 2 NPs caused the highest damage to genomic DNA and mitochondrial membrane potential, less genomic DNA and mitochondrial damage was induced by CaTiO 3 NPs administration while administration of Y 2 O 3 NPs 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) 2 NPs but Y 2 O 3 NPs administration almost caused no changes in ROS generation and genes expression compared to the negative control. Administration of CaTiO 3 NPs 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 Y 2 O 3 NPs with Ca(OH) 2 NPs and CaTiO 3 NPs. Coadministration of Y 2 O 3 NPs with Ca(OH) 2 NPs and CaTiO 3 NPs mitigated Ca(OH) 2 NPs and CaTiO 3 NPs induced ROS generation, genomic DNA damage and inflammation along with restoring the integrity of mitochondrial membrane potential through Y 2 O 3 NPs scavenging free radicals ability. Therefore, further studies are recommended to study the possibility of using Y 2 O 3 NPs to alleviate Ca(OH) 2 NPs and CaTiO 3 NPs induced genotoxic effects., (© 2024. The Author(s).)

Titanium dioxide nanoparticles (TiO 2 -NPs) have found wide applications in medical and industrial fields. However, the toxic effect of various tissues is still under study. In this study, we evaluated the toxic effect of TiO 2 -NP on stomach, liver, and kidney tissues and the amelioration effect of clove oil nanoemulsion (CLV-NE) against DNA damage, oxidative stress, pathological changes, and the apoptotic effect of TiO 2 -NPs. Four groups of male mice were subjected to oral treatment for five consecutive days including, the control group, the group treated with TiO 2 -NPs (50 mg/kg), the group treated with (CLV-NE) (5% of the MTD), and the group treated with TiO 2 -NPs plus CLV-NE. The results revealed that the treatment with TiO 2 -NPs significantly 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 effect confirmed by the significant elevation of p53 expression were reported after TiO 2 -NPs administration. The present data reported a significant improvement in the previous parameters after treatment with CLV-NE. These results showed the collaborative effect of the oils and the extra role of nanoemulsion in enhancing antioxidant effectiveness 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 effects of the acute use of TiO 2 -NPs., (© 2024. The Author(s).)

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 (CaTiO 3 ), and yttrium oxide (Y 2 O 3 ) 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 , CaTiO 3, or/and Y 2 O 3 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 , CaTiO 3, or Y 2 O 3 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 CaTiO 3 or Y 2 O 3 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 CaTiO 3 and Y 2 O 3 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 CaTiO 3 and Y 2 O 3 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 CaTiO 3 and Y 2 O 3 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 , CaTiO 3 and Y 2 O 3 nanoparticles and possibility of using CaTiO 3 and Y 2 O 3 nanoparticles to mitigate genotoxicity and inflammation induction by Ca(OH) 2 nanoparticles., (© 2023. The Author(s).)

Iron overload (IOL) can cause hepatorenal damage due to iron-mediated oxidative and mitochondrial damage. Remarkably, combining a natural iron chelator with an antioxidant can exert greater efficacy than monotherapy. Thus, the present study aimed to evaluate the efficacy of Chia and CoQ 10 to chelate excess iron and prevent hepatorenal oxidative damage in IOL mice. Male Swiss albino mice (n = 49) were randomly assigned to seven groups: control, dietary Chia, CoQ 10 , IOL, IOL + Chia, IOL + CoQ 10 , and IOL + Chia + CoQ 10 . Computational chemistry indicates that the phytic acid found in the Chia seeds is stable, reactive, and able to bind to up to three iron ions (both Fe 2+ and Fe 3+ ). IOL induced a significant (P < 0.05) increase in serum iron, ferritin, transferrin, TIBC, TSI, RBCs, Hb, MCV, MCH, WBCs, AST, ALT, creatinine, and MDA. IOL causes a significant (P < 0.05) decrease in UIBC, platelets, and antioxidant molecules (GSH, SOD, CAT, and GR). Also, IOL elicits mitochondrial membrane change depolarization, and DNA fragmentation and suppresses mitochondrial DNA copies. Furthermore, substantial changes in hepatic and renal tissue, including hepatocellular necrosis and apoptosis, glomerular degeneration, glomerular basement membrane thickening, and tubular degeneration, were observed in the IOL group. Dietary Chia and CoQ 10 induced significant (P < 0.05) amelioration in all the mentioned parameters. They can mostly repair the abnormal architecture of hepatic and renal tissues induced by IOL, as signified by normal sinusoids, normal central veins, and neither glomerular damage nor degenerated tubules. In conclusion, the combined treatment with Chia + CoQ 10 exerts more pronounced efficacy than monotherapy in hepatorenal protection via chelating excess iron and improved cellular antioxidant status and hepatorenal mitochondrial function in IOL mice., (© 2023. The Author(s).)

Intensive uses of Calcium hydroxide (Ca(OH) 2 NPs), calcium titanate (CaTiO 3 NPs) and yttrium oxide (Y 2 O 3 NPs) 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 effect of Ca(OH) 2 NPs, CaTiO 3 NPs or/and Y 2 O 3 NPs administration on the genotoxicityand oxidative stress induction in mice hepatic tissue. Mice were orally administered Ca(OH) 2 NPs, CaTiO 3 NPs and Y 2 O 3 NPs 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) 2 NPs or CaTiO 3 NPs alone together with high Ca(OH) 2 NPs induced reactive oxygen species (ROS) generation and a slight CaTiO 3 NPs induced ROS production were highly decreased after simultaneous coadministration of administration of Y 2 O 3 NPs with Ca(OH) 2 NPs and CaTiO 3 NPs up to the negative control level. Oral administration of Y 2 O 3 NPs alone also did not cause observable changes in the genomic DNA integrity and the ROS generation level compared to the negative control levels. Similarly, significant elevations in P53 gene expression and high reductions in Kras and HSP-70 genes expression were observed only after administration of Ca(OH) 2 NPs alone, while, remarkable increases in the Kras and HSP-70 genes expression and non-significant changes in p53 gene expression were noticed after administration of CaTiO 3 NPs and Y 2 O 3 NPs separately or simultaneously together with Ca(OH) 2 NPs. Conclusion: Ca(OH) 2 NPs exhibited the highest genotoxic effect through oxidative stress induction and disruption of apoptotic (p53 and Kras) and protective (HSP-70) genes expression. Slight DNA damage was noticed after CaTiO 3 NPs administration. However, administration of Y 2 O 3 NPs alone was non-genotoxic and coadministration of Y 2 O 3 NPs with Ca(OH) 2 NPs and CaTiO 3 NPs restored genomic DNA integrity and normal expression of apoptotic p53 and protective HSP-70 genes disrupted by Ca(OH) 2 NPs and CaTiO 3 NPs. Thus co-administration of Y 2 O 3 NPs with Ca(OH) 2 NPs and CaTiO 3 NPs is recommended to counter Ca(OH) 2 NPs and CaTiO 3 NPs induced genotoxicity and oxidative stress., (© 2023. The Author(s).)

The Kidneys remove toxins from the blood and move waste products into the urine. However, the accumulation of toxins and fluids in the body leads to kidney failure. For example, the overuse of acrylamide and titanium dioxide nanoparticles (TiO 2 NPs) in many food and consumer products increases human exposure and risks; however, there are almost no studies available on the effect of TiO 2 NPs 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 TiO 2 NPs. To achieve this goal, mice were administrated orally TiO 2 NPs or/and acrylamide at the exposure dose levels (5 mg/kg b.w) and (3 mg/kg b.w), respectively, five times per week for two consecutive weeks. Concurrent oral administration of TiO 2 NPs 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 TiO 2 NPs alone. Simultaneous coadministration of TiO 2 NPs 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 findings, we concluded that concurrent coadministration of acrylamide with TiO 2 NPs augmented TiO 2 NPs 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 effects resulting from TiO 2 NPs with acrylamide coadministration., (© 2023. Springer Nature Limited.)

Extensive uses of calcium titanate nanoparticles (CaTiO 3 -NPs) and erbium oxide nanoparticles (Er 2 O 3 -NPs) increase their release into the environment and human exposure, particularly through skin contact. However, there are almost no studies available on the effect of these nanoparticles on skin integrity. Therefore, this study was undertaken to estimate CaTiO 3 -NP- or Er 2 O 3 -NP-induced cytotoxicity and genotoxicity in normal human skin fibroblast (HSF) cells. Cell viability was measured using sulforhodamine B (SRB) assay, while the level of DNA damage was detected using the alkaline comet assay. The intracellular levels of reactive oxygen species (ROS) as well as the expression level of p53, Bax, and Bcl2 genes were detected. Although the viability of HSF cells was non-markedly changed after 24 h, prolonged treatment with CaTiO3-NPs or Er2O3-NPs for 72 h induced concentration-dependent death of HSF cells. Treatment of normal HSF cells with IC50/72 h of CaTiO3-NPs or Er2O3-NPs did not cause marked changes in the intracellular level of ROS, DNA damage parameters, and expression levels of apoptosis genes compared to their values in the untreated HSF cells. We thus concluded that CaTiO3-NPs or Er2O3-NPs cause time- and concentration-dependent cytotoxicity toward normal HSF cells. However, safe and non-genotoxic effects were demonstrated by the apparent non-significant changes in intracellular ROS level, DNA integrity, and apoptotic genes' expression after exposure of normal HSF cells to nanoparticles. Thus, it is recommended that further studies be conducted to further understand the toxic and biological effects of CaTiO 3 -NPs and Er2O3-NPs., (© 2022. The Author(s).)

Despite the high antioxidant and penetration ability of pomegranate seed oil (PSO), the in vivo antitumor activity of PSO nano-emulsion has not been well investigated. Therefore, this study was undertaken to estimate the antitumor activity and safety of PSO nano-emulsion in mice bearing Ehrlich solid carcinoma cells. For tumor inoculation, about 2 × 10 6 viable Ehrlich tumor cells (200 µl) were implanted intramuscularly in the left thigh of hind leg. Once a solid tumor appears on the 10th day of transplantation; the mice were randomly divided into five groups (5 animals/group). Characterization of the PSO nano-emulsion using a Zeta sizer Malvern instrument and transmission electron microscope (TEM) revealed that the PSO nano-droplets were well dispersed with an average particle size of 8.95 nm and a spherical shape. Treatment with PSO nano-emulsions caused a significant reduction in the tumor size and weight, in a dose dependent manner, compared to tumor control group. Marked dose dependent elevations in the DNA damage level together with significant increases in the tumor suppressor p53, Bax and Caspase genes and reductions in the anti-apoptotic Bcl2 gene were also observed in the tumor tissue of mice given PSO nano-emulsions. Histological examination also revealed apoptosis and necrosis of tumor cells and tumor infiltration with inflammatory cells after PSO nano-emulsion treatment. However, high DNA damage was noticed in the liver and kidney tissues of mice given the highest dose of PSO nano-emulsion (400 mg/kg). Therefore, we concluded that PSO nano-emulsion exhibited a potent antitumor activity through induction of DNA breaks that triggers apoptosis of tumor cells but the highest dose caused genotoxicity to liver and kidney tissues, thus it is recommended to use doses lower than 400 mg/kg of PSO nano-emulsion as an alternative drugs for chemotherapy., (© 2023. The Author(s).)

Background: The distinctive properties and high activity of calcium titanate nanoparticles (CaTiO 3 -NPs) increase their use in many products. However, the cytotoxic and genotoxic effects of CaTiO 3 -NPs in human cancer cell lines have not been well studied. Therefore, this study was conducted to explore CaTiO 3 -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 flow 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 affected by CaTiO 3 -NPs treatment for 24 h, however, exposure to CaTiO 3 -NPs for 72 h caused concentrations dependent death of MCF-7 cells. Treatment with CaTiO 3 -NPs for 72 h caused marked increases in intracellular ROS level and induced DNA damage. Treatment of MCF-7 cells with CaTiO 3 -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 apoptotic p53 and Bax genes and a decrease in the expression level of anti-apoptotic Bcl2 gene., Conclusion: Collectively, it was concluded that CaTiO 3 -NPs cause time- and concentration-dependent cytotoxic effects 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 effects of CaTiO 3 -NPs., (© 2022. The Author(s).)

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 (TiO 2 NPs) are widely used in toothpaste, sweets, food perseveration, chewing gum and medicines. Consequently, humans are daily exposed to large amounts of acrylamide and TiO 2 NPs mainly through food intake. However, limited studies are available on the effect of simultaneously intake of acrylamide and TiO 2 NPs on the integrity of genomic DNA and the induction of apoptosis in brain tissues. Therefore, this study estimated the influence of acrylamide coadministration on TiO 2 NPs 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 TiO 2 NPs (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 TiO 2 NPs 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 TiO 2 NPs compared to those observed after administration of acrylamide or/TiO 2 NPs alone. Moreover, oral co-administration of acrylamide with TiO 2 NPs 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 TiO 2 NPs. Therefore, from these results, the present study concluded that coadministration of acrylamide renders TiO 2 NPs more genotoxic and motivates apoptotic DNA damage and oxidative stress induced by TiO 2 NPs in brain cells, and thus it is recommended to avoid concurrent oral acrylamide administration with TiO 2 NPs., (© 2022. The Author(s).)

The impacts of the Batts drain on two chronically exposed fish (O. niloticus and C. gariepinus) were assessed using multiple biomarkers. Concentrations of metals in water and sediments (Cu, Zn, Fe, Cd, Pb, and Al) showed significant elevations near the Batts discharges (site 2) compared to the reference site (site 1). The liver and gills of fish collected from site 2 showed marked elevations in the catalase, superoxide dismutase, glutathione peroxidase, and thiobarbituric acid reactive substance levels. In addition, significant reductions in glutathione-reduced contents were also recorded. Tissue and species-specific antioxidant responses were associated with excessive generations of reactive oxygen species, which were visualized fluorescently. Various histological alterations were observed in the gills and livers of both species. These alterations varied between compensatory responses (ex: epithelial thickening and lifting) and irreversible damage (ex: necrotic degeneration). Based on the level of lipid peroxidation and the frequency of histopathological modifications, O. niloticus demonstrated greater resistance to the same level of pollution than C. gariepinus. Using integrated biomarkers to evaluate the real impacts of untreated discharges of the Batts drain is applied for the first time on the selected fish species at the studied sites., (© 2022. The Author(s).)

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 scientific interest in using erbium oxide nanoparticles (Er 2 O 3 -NPs) and other noble metal nanostructures in cancer treatment. However, the therapeutic effect of Er 2 O 3 -NPs on hepatic cancer cells has not been studied. Therefore, the current study was conducted to estimate the therapeutic potential of Er 2 O 3 -NPs on human hepatocellular carcinoma (Hep-G2) cells. Exposure to Er 2 O 3 -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 Er 2 O 3 -NPs in Hep-G2 cells. As determined by flow cytometry, Er 2 O 3 -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, Er 2 O 3 -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 Er 2 O 3 -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., (© 2022. The Author(s).)

Increased human exposure to cadmium compounds through ingesting contaminated food, water, and medications causes negative long-term health effects, which has led to the focus of recent researches on finding natural antioxidants to mitigate cadmium-induced toxicity. Therefore, the current study was undertaken to estimate the possible ameliorative effect of chocolate coadministration on acute cadmium chloride (CdCl 2 )-induced genomic instability and mitochondrial DNA damage in mice liver and kidney tissues. Concurrent administration of chocolate with CdCl 2 dramatically decreased the DNA damage level and the number of apoptotic and necrotic cells compared to mice given CdCl 2 alone. Extra-production of reactive oxygen species and increased expression of inducible nitric oxide synthase and heat shock proteins genes caused by CdCl 2 administration were also highly decreased after chocolate coadministration. Conversely, chocolate coadministration restored the integrity of the mitochondrial membrane potential disrupted by CdCl 2 administration, as well as the mitochondrial DNA copy number and expression level of heme oxygenase-1 gene were significantly upregulated after chocolate coadministration with CdCl 2 . Thus, it was concluded that the coadministration of chocolate alleviated CdCl 2 -induced genomic instability and mitochondrial DNA damage through its antioxidative and free radical scavenging capabilities, making chocolate a promising ameliorative product and recommended for inclusion in the daily human diet., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Lead, a highly toxic pollutant, causes numerous health problems and affects nearly all biological systems thus arousing interest in using antioxidants to reduce its toxic effects. Therefore, the undertaken study estimated the influence of cerium oxide nanoparticles (CeO 2 -NPs) on the lead acetate-induced genotoxicity and inflammation in the kidney and heart tissues of mice. Twenty male mice were randomly divided into negative control and lead acetate and/or CeO 2 -NPs administrated groups. Comet and diphenylamine assays were conducted to assess the DNA damage and the expression of apoptosis-related genes and inflammatory cytokines were also measured in addition to the estimation of reactive oxygen species (ROS) level. Co-administration of CeO 2 -NPs significantly reduced the DNA damage and ROS generation caused by lead acetate in the kidney and heart tissues. The co-administration of CeO 2 -NPs also ameliorated the lead acetate-induced dysregulation in the expression levels of p53, K-ras, interleukin-6, and cyclooxygenase-2 in the kidney and heart. Conclusion: the co-administration of CeO 2 -NPs suppresses the genotoxicity, inflammation, and ROS generation resulting from lead acetate administration and restoring the genomic DNA integrity; thus, administration of CeO 2 -NPs is recommended to minimize the lead acetate-induced hazards., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Nicotine is the most abundant ingredient in cigarette smoking and has serious side effects on the lung, heart, reproductive system, and many other human organs. Saponins extracted from many plants exhibit multiple biological actions such as anti-cancer effects. Therefore, the possible protective effect of fenugreek saponin (FS) and nanofenugreek saponin (NFS) against nicotine-induced toxicity in male rats was investigated in this study. Animals were divided into a control group and the nicotine (1.5 mg/kg/day), FS (25, 50, and 100 mg/kg/day), or/and NFS (20, 40, and 80 mg/kg/day) administered groups. Micronucleus assay, histopathological, and sperm abnormality examinations as well as measurement of the acetylcholinesterase (AChE) gene expression were conducted. Our findings revealed that nicotine treatment induced significant increases in the incidence of micronucleus, sperm abnormalities, and expression levels of AChE in addition to inducing histopathological changes in rat testis. On the other hand, administration of FS or NFS with nicotine significantly decreased the incidence of micronuclei and the percentage of sperm abnormalities as well as the expression levels of AChE gene. Moreover, nicotine-induced histological alterations were reduced by given FS or NFS with nicotine. In conclusion, nicotine-induced sperm abnormalities, chromosomal damage, and histological injuries were mitigated by administration of FS or NFS with nicotine, and thus, FS and NFS could be used as ameliorating agents against nicotine toxicity., (© 2022. The Author(s).)

The current study aimed to investigate the relationship between polymorphisms in detoxifying (GSTM1, GSTT1, and GSTP1) genes and their association with colorectal cancer (CRC) in tobacco addicts of Pashtun ethnicity. Polymorphisms in the selected genes were genotyped in a case-control study consisting of 100 histologically confirmed male CRC patients and 100 birth-year and gender-matched healthy controls using the PCR-RFLP method. The GSTM1 null, and GSTT1 null genotypes were significantly contributed to the risk of CRC in the cases (OR= 3.131, 95% CI: 1.451-6.758, P = 0.004, and OR= 3.541, 95% CI: 1.716-7.306, P = 0.001, respectively), whereas the association observed for GSTP1 Val/Val (1.139, 95% CI: 0.356-3.644, P = 0.826) did not show statistical significance. The combined GSTM1 null and GSTT1 null showed a 41-fold increased risk (95% CI: 4.945-351.950, P = 0.001), while, the combined GSTM1 null and GSTP1 Ile/Val or Val/Val variant genotypes exhibited about 3-fold (95% CI: 1.196-7.414, P = 0.019) increased risk to CRC. Similarly, the combined GSTT1 null and GSTP1 Ile/Val or Val/Val variant genotypes showed about a 3-fold (95% CI: 1.285-8.101, P = 0.013) increased risk of CRC. In the combination of three GST genotypes, the GSTM1 null, GSTT1 null, and GSTP1 Ile/Val or Val/Val variant genotypes demonstrated a more than a 22-fold (95% CI: 2.441-212.106, P = 0.006) increased risk of CRC. Our findings suggest that GSTM1 and GSTT1 polymorphism and its combination with GSTP1 may be associated with CRC susceptibility in the Naswar addicted Pashtun population of Khyber Pakhtunkhwa, Pakistan.

The present work showed the impact of long-term exposure to the Batts drain's discharges on O. niloticus and C. gariepinus fish species. The accumulation level of Cu, Zn, Fe, Cd, Pb and Al in five vital tissues was markedly elevated near the Batts drain (site2) compared to the samples from the reference site (site 1). At the same site, C. gariepinus displayed the highest accumulation capacities when compared to O. niloticus. Based on the metal pollution index, livers and kidneys, followed by gills, showed the maximum overall metal load. The degree of DNA damage (assessed by comet and diphenylamine assays) was relative to the accumulated metals in tissues with species and site specification. The values of the hazard index for human consumption showed that the studied metals were within safe values at normal consumption rates. While harmful health consequences were observed at the habitual consumption level at site 2., (© 2022. The Author(s).)

Background: Lung diseases including chronic obstructive pulmonary disease (COPD), infections like influenza, acute respiratory distress syndrome (ARDS), asthma and pneumonia lung cancer (LC) are common causes of sickness and death worldwide due to their remoteness, cold and harsh climatic conditions, and inaccessible health care facilities., Purpose: Many drugs have already been proposed for the treatment of lung diseases. Few of them are in clinical trials and have the potential to cure infectious diseases. Plant extracts or herbal products have been extensively used as Traditional Chinese Medicine (TCM) and Indian Ayurveda. Moreover, it has been involved in the inhibition of certain genes/protiens effects to promote regulation of signaling pathways. Natural remedies have been scientifically proven with remarkable bioactivities and are considered a cheap and safe source for lung disease., Methods: This comprehensive review highlighted the literature about traditional plants and their metabolites with their applications for the treatment of lung diseases through experimental models in humans. Natural drugs information and mode of mechanism have been studied through the literature retrieved by Google Scholar, ScienceDirect, SciFinder, Scopus and Medline PubMed resources against lung diseases., Results: In vitro, in vivo and computational studies have been explained for natural metabolites derived from plants (like flavonoids, alkaloids, and terpenoids) against different types of lung diseases. Probiotics have also been biologically active therapeutics against cancer, anti-inflammation, antiplatelet, antiviral, and antioxidants associated with lung diseases., Conclusion: The results of the mentioned natural metabolites repurposed for different lung diseases especially for SARS-CoV-2 should be evaluated more by advance computational applications, experimental models in the biological system, also need to be validated by clinical trials so that we may be able to retrieve potential drugs for most challenging lung diseases especially SARS-CoV-2., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Neurodegenerative disorders (NDs) including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis have various disease-specific causal factors and pathological features. A very common characteristic of NDs is oxidative stress (OS), which takes place due to the elevated generation of reactive oxygen species during the progression of NDs. Furthermore, the pathological condition of NDs including an increased level of protein aggregates can further lead to chronic inflammation because of the microglial activation. Carotenoids (CTs) are naturally occurring pigments that play a significant role in averting brain disorders. More than 750 CTs are present in nature, and they are widely available in plants, microorganisms, and animals. CTs are accountable for the red, yellow, and orange pigments in several animals and plants, and these colors usually indicate various types of CTs. CTs exert various bioactive properties because of its characteristic structure, including anti-inflammatory and antioxidant properties. Due to the protective properties of CTs, levels of CTs in the human body have been markedly linked with the prevention and treatment of multiple diseases including NDs. In this review, we have summarized the relationship between OS, neuroinflammation, and NDs. In addition, we have also particularly focused on the antioxidants and anti-inflammatory properties of CTs in the management of NDs., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Cosmetic-containing herbals are a cosmetic that has or is claimed to have medicinal properties, with bioactive ingredients purported to have medical benefits. There are no legal requirements to prove that these products live up to their claims. The name is a combination of "cosmetics" and "pharmaceuticals". "Nutricosmetics" are related dietary supplements or food or beverage products with additives that are marketed as having medical benefits that affect appearance. Cosmetic-containing herbals are topical cosmetic-pharmaceutical hybrids intended to enhance the health and beauty of the skin. Cosmetic-containing herbals improve appearance by delivering essential nutrients to the skin. Several herbal products, such as cosmetic-containing herbals, are available. The present review highlights the use of natural products in cosmetic-containing herbals, as natural products have many curative effects as well as healing effects on skin and hair growth with minimal to no side effects. A brief description is given on such plants, their used parts, active ingredients, and the therapeutic properties associated with them. Mainly, the utilization of phytoconstituents as cosmetic-containing herbals in the care of skin and hair, such as dryness of skin, acne, eczema, inflammation of the skin, aging, hair growth, and dandruff, along with natural ingredients, such as for hair colorant, are explained in detail in the present review.

In this study, a first attempt has been made to deliver levosulpiride transdermally through a thiolated chitosan microneedle patch (TC-MNP). Levosulpiride is slowly and weakly absorbed from the gastrointestinal tract with an oral bioavailability of less than 25% and short half-life of about 6 h. In order to enhance its bioavailability, levosulpiride-loaded thiolated chitosan microneedle patches (LS-TC-MNPs) were fabricated. Firstly, thiolated chitosan was synthesized and characterized by nuclear magnetic resonance ( 1 HNMR) spectroscopy, attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD). Thiolated chitosan has been used in different drug delivery systems; herein, thiolated chitosan has been used for the transdermal delivery of LS. LS-TC-MNPs were fabricated from different concentrations of thiolated chitosan solution. Furthermore, the levosulpiride-loaded thiolated chitosan microneedle patch (LS-TC-MNP) was characterized by FTIR spectroscopic analysis, scanning electron microscopy (SEM) study, penetration ability, tensile strength, moisture content, patch thickness, and elongation test. LS-TC-MNP fabricated with 3% thiolated chitosan solution was found to have the best tensile strength, moisture content, patch thickness, elongation, drug-loading efficiency, and drug content. Thiolated chitosan is biodegradable, nontoxic and has good absorption and swelling in the skin. LS-TC-MNP-3 consists of 100 needles in 10 rows each with 10 needles. The length of each microneedle was 575 μm; they were pyramidal in shape, with sharp pointed ends and a base diameter of 200 µm. The microneedle patch (LS-TC-MNP-3) resulted in-vitro drug release of 65% up to 48 h, ex vivo permeation of 63.6%, with good skin biocompatibility and enhanced in-vivo pharmacokinetics (AUC = 986 µg/mL·h, Cmax = 24.5 µg/mL) as compared to oral LS dispersion (AUC = 3.2 µg/mL·h, Cmax = 0.5 µg/mL). Based on the above results, LS-TC-MNP-3 seems to be a promising strategy for enhancing the bioavailability of levosulpiride.

Curcumin is the primary polyphenol in turmeric's curcuminoid class. It has a wide range of therapeutic applications, such as anti-inflammatory, antioxidant, antidiabetic, hepatoprotective, antibacterial, and anticancer effects against various cancers, but has poor solubility and low bioavailability. Objective: To improve curcumin's bioavailability, plasma concentration, and cellular permeability processes. The nanocurcumin approach over curcumin has been proven appropriate for encapsulating or loading curcumin (nanocurcumin) to increase its therapeutic potential. Conclusion: Though incorporating curcumin into nanocurcumin form may be a viable method for overcoming its intrinsic limitations, and there are reasonable concerns regarding its toxicological safety once it enters biological pathways. This review article mainly highlights the therapeutic benefits of nanocurcumin over curcumin.

The unique physicochemical properties of graphene oxide (GO) nanoparticles increase their uses in a wide range of applications that increase their release into the environment, and thus human exposure. However, the in vivo clastogenicity and genotoxicity of GO nanoparticles have not been well investigated. The current study was, therefore, designed to investigate the possible induction of chromosomal and DNA damage by GO nanoparticles and their impact on the tissue architecture in mice. Oral administration of GO nanoparticles for one or five consecutive days at the three dose levels 10, 20 or 40 mg/kg significantly increased the micronuclei and DNA damage levels in a dose-dependent manner in mice bone marrow cells, as well as caused, histological lesions including apoptosis, necrosis, inflammations and cells degeneration in the mice liver and brain tissue sections compared to the normal control mice. Thus, we concluded that oral administration of GO nanoparticles induced chromosomal and DNA damage in a dose-dependent manner as well as histological injuries in both acute and subacute treatments.

With the high increases in the uses of calcium hydroxide in various applications due its distinctive properties, human exposure has increased to normal- and nano-calcium hydroxide. However, its impact on the DNA integrity, expression of inflammatory cytokines, and induction of oxidative stress has not been clearly studied. Therefore, here we estimate the induction of DNA damage, inflammation, and oxidative stress in mice orally administrated a single dose (100 mg/kg) of normal- or nano-sized calcium hydroxide for 24 hour. Comet, Diphenylamine and laddered DNA fragmentation assays were done to assess DNA damage induction. Acute oral administration of normal- or nano-calcium hydroxide particles disrupted the DNA integrity, caused generation of ROS and also concurrent increases in both the nitric oxide concentration and inducible nitric oxide synthase gene expression in a reverse proportional to the calcium hydroxide particles' size. Increases in the concentration of calcium ions as well as alterations in the expression level of p53 and proinflammatory cytokines were also observed in calcium hydroxide administrated groups. Moreover, administration of normal- or nano-calcium hydroxide particles suspension elevated the level of malondialdehyde and decreased both the glutathione peroxidase activity and the reduced glutathione level, as well as caused tissue injuries (e.g. renal tube degeneration, congested blood vessels, atrophied lymphoid follicles, interstitial inflammatory reaction, and hyalinosis of myocardial muscles). Thus, we conclude that calcium hydroxide acutely orally administrated in its ordinary or nano-particulate form causes DNA damage induction by generating free radicals and altering the expression levels of p53 gene and proinflammatory cytokines.

The low price and high contents of bioactive compounds in citrus peel increase interest in using it in various applications. Mandarin (Citrus reticluata) peel belongs to Rutaceae family and is rich with antioxidants. However, limited studies are available on toxicity of Mandarin peel oil (MPO) on human Prostate Cancer (PC3) cells. Therefore, the present study was conducted to study the cytotoxicity and genotoxicity of MPO on Human normal Fibroblast (HFB4) and PC3 cell lines. The half maximal inhibitory (IC50) and safe concentration of MPO was detected using MTT assay. Comet and DNA fragmentation assays were performed to assess apoptotic DNA damage. Also, the ROS level was evaluated and the mRNA expression level of apoptotic and antiapoptotic genes were measured using RT-PCR. Results of the cytotoxic test showed that MPO induced preferential inhibition of PC3 cells proliferation in a concentration-dependent manner with IC50 10.97 µg/ml. The time-dependent induction of DNA breaks demonstrated in PC3 cells treated with MPO safe concentration-stimulated ROS generation and apoptotic DNA damage through increased expression of tumor suppressor p53 and Bax genes and decreased expression of Bcl2 and MDM2 genes. In contrast, non-significant changes were observed in the DNA integrity, ROS levels and expressions of the tested genes in the normal HFB4 cells treated with MPO. Thus, we concluded that MPO induced preferential cytotoxic and genotoxic effects toward cancerous PC3 with no noticeable toxic effects in normal HFB4 cells and therefore further in vivo studies are recommended to test its possible use as anticancer drugs.

Increasing the uses of molybdenum (Mo) nanoparticles in a wide range of applications including food, industry, and medicine, resulted in increased human exposure and necessitated the study of their toxic effects. However, almost no studies are available on their genotoxic effects, especially on pregnant females and their fetuses. Therefore, this study was undertaken to estimate the possible induction of genotoxicity and fetal abnormalities, especially fetal malformations and skeletal abnormalities by Mo nanoparticle administration in mice. Oral administration of Mo nanoparticles resulted in significant decreases in the maternal body weight, the number and length of fetuses as well as skeletal abnormalities mainly less ossification and less chondrification. Administration of Mo nanoparticles also caused DNA damage induction which elevated the expression levels of p53, the vital gene in maintaining the genomic stability and cell differentiation in both maternal and fetus tissues. Similarly, the expression levels of E-Cad and N-Cad genes that control skeleton development have also been increased in the tissues of female mice administered Mo nanoparticles and their fetuses. Thus, we concluded that oral administration of Mo nanoparticles induced genotoxic effects and fetal abnormalities that necessitated further studies on the possible toxic effects of Mo nanoparticles.

The rapidly growing interest in using graphene-based nanoparticles in a wide range of applications increases human exposure and risk. However, very few studies have investigated the genotoxicity and mutagenicity of the widely used graphene oxide (GO) nanoparticles in vivo. Consequently, this study estimated the possible genotoxicity and mutagenicity of GO nanoparticles as well as possible oxidative stress induction in the mice liver and brain tissues. Nano-GO particles administration at the dose levels of 10, 20, or 40 mg/kg for one or five consecutive days significantly increased the DNA breakages in a dose-dependent manner that disrupts the genetic material and causes genomic instability. GO nanoparticles also induced mutations in the p53 (exons 6&7) and presenilin (exon 5) genes as well as increasing the expression of p53 protein. Positive p53 reaction in the liver (hepatic parenchyma) and brain (cerebrum, cerebellum, and hippocampus) sections showed significant increase of p53 immunostaining. Additionally, induction of oxidative stress was proven by the significant dose-dependent increases in the malondialdehyde level and reductions in both the level of reduced glutathione and activity of glutathione peroxidase observed in GO nanoparticles administered groups. Acute and subacute oral administration of GO nanoparticles induced genomic instability and mutagenicity by induction of oxidative stress in the mice liver and brain tissues.

Nowadays, there is increasing interest in using calcium hydroxide (Ca(OH) 2 ) nanoparticles rather than normal-sized Ca(OH) 2 because of its higher antimicrobial activities. However, the genotoxicity of Ca(OH) 2 nanoparticles has not been well investigated. Therefore, this study was performed to estimate the possible genomic instability and mitochondrial DNA damage induction by normal and nano-sized Ca(OH) 2 particles in mice. Oral administration of normal or nano-sized Ca(OH) 2 particles induced DNA breakages and apoptosis causing genomic instability as a result of increased Calcium content, ROS and MDA levels and decreased SOD and Gpx activities reversely proportional to Ca(OH) 2 particles size in the liver, brain and bone marrow tissues. However, decreases in mitochondrial membrane potential concurrently with downregulated expression of POLG, POLG1 and TFAM genes were only observed in the brain and bone marrow tissues confirmed mitochondrial DNA damage. In contrast, the expressions of POLG, POLG1 and TFAM genes have been improved and mitochondrial membrane potential has not unchanged in liver tissues. Conclusion: single oral administration of normal or nano-sized Ca(OH) 2 particles induced genomic instability through ROS generation that exhausted the antioxidant defense system in the liver, brain and bone marrow tissues but impaired the mitochondrial DNA only in the brain and bone marrow tissues., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The present study was conducted to investigate the effect of incorporating Cicer arietinum in the diet on the testicular functions of the male mice. Seventy-two mice were divided equally into four groups that were daily fed a diet containing 0, 20, 30 and 50% of C. arietinum seeds, respectively. After 7, 14 and 21 days of starting the experiments, the mice were anesthetized and euthanized to collect the blood, testes, epididymis and seminal vesicles. The present results showed that the increased percentage of C. arietinum in the diet caused significant elevations in the serum levels of testosterone and luteinizing hormone (LH), sperm concentration, sperm motility as well as the testicular levels of antioxidants including glutathione (GSH), glutathione peroxidase (GPx) and catalase (CAT), in comparison to the controls. On the other hand, marked reductions in the sperm abnormality, testicular levels of malondialdehyde (MDA), the percentage of DNA damage in tail and tail moment (TM) were observed in the mice that received a diet containing C. arietinum as compared to the controls. Both the sperms and testes of the mice fed a diet containing C. arietinum in the diet showed a normal intact appearance of the electrophoresed genomic DNA on agarose, as those of the controls. In conclusion, C. arietinum is not only a safe ingredient in the fast-food but also an enhancer of the testicular functions.

This study was carried out to study the diet type, genetic, morphometric and histological variations between two natural populations of Trachylepis quinquetaeniata inhabiting Abu-Rawash, Embaba, North Giza and Garfas-Senoures, El-Faiyum habitats. In this study, morphometric examination showed that Trachylepis quinquetaeniata is a typically ground-dwelling Skink and seems to be frequently associated with grass and below shrubs. Geographic variation in sexual size dimorphism (SSD) and head size dimorphism (HSD) with greater dimensions in Garfas-Senoures, El-Faiyum compared with Abu-Rawash, Embaba, North Giza might be correlated with spatial food availability and abundance or micro-evolutionary change or phenotypic plasticity. Also, the increase of body size and mass in individuals from Garfas-Senoures, El-Faiyum might be an adaptation to lower ambient temperature and hypoxia. Diet analysis showed that the bulk of gut contents were beetles, plant bugs, hymenopterans and dipterans. The remainder of the plant material was probably ingested secondarily. Moreover, the increase in the activity of Ldh in liver tissues of T. quinquetaeniata inhabiting Abu-Rawash, Embaba, North Giza could be confirmed by the significant increase in the accumulation of the total lipids in liver and muscle tissues than that in the other population. As well as, a marked degeneration, necrosis and desquamation of spermatogoneal cells lining seminiferous tubules in testes of T. quinquetaeniata inhabiting Garfas-Senoures, El-Faiyum than that in the other population inhabiting Abu-Rawash, Embaba, North Giza that could be attributed to the bioaccumulation of soil heavy metals in testes. Higher carbohydrate accumulation in the former lizards' population was confirmed by the high availability and diversity of diet in El-Faiyum habitat. Thus we concluded that T. quinquetaeniata inhabiting Abu-Rawash, Embaba, North Giza is more active, energetic and adaptable in its habitat than T. quinquetaeniata inhabiting Garfas-Senoures, El-Faiyum.

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.

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.