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Abstract: Aflatoxins (AFs), a group of closely related, extremely toxic mycotoxins produced by Aspergillus flavus and A. parasiticus, can occur as natural contaminants of food and feeds. AFs have been shown to be hepatotoxic, carcinogenic, mutagenic and teratogenic to different animal species. In the current study Tunisian montmorillonite (TM) was evaluated versus AFs caused toxicities in human colon cancer cell line (Caco-2) and in rats as a sensitive model. The aims of this study were threefold: (1) to evaluate the efficacy of TM to adsorb AFs from aqueous solution, (2) to protect Caco-2 cell line against AFs-induced cytotoxicity, DNA fragmentation and caspase-3-dependent apoptosis induction and (3) to evaluate the protective effect of TM against AFs toxicity in Sprague–Dawley rats. In the in vitro study, three concentrations of TM (0.5, 1, and 2 mg/L aqueous solution) and three concentrations of AFB1 (10, 20, 50 mg/L) were tested. The results indicated that TM had a high capacity of adsorbing AFB1 at different concentrations tested. The quantity adsorbed was 19.26 mg of AFB1/g of TM. TM protects Caco-2 cells, inhibits DNA fragmentation and reduces caspase-3 enzymes activity in aflatoxin-treated Caco-2 cell culture. The in vivo results indicated that rats fed AFs-contaminated diet (2.5 mg kg−1 diet) for 2 weeks showed severe serum biochemical changes typical of aflatoxicosis. Rats treated with TM alone (5%) or in combination with aflatoxin were comparable to the control. The TM was found to be safe and successful in the prevention of aflatoxin toxicity and cytotoxicity. [Copyright &y& Elsevier]

Ethylenediaminetetraacetic acid (EDTA) is widely used in food and other industries to sequester metal ions and to prevent their disadvantageous effects. The objective of the current study was to evaluate the protective effect of Panax ginseng extract standardized with ginsenoside Rg3 (ginsenoside Rg3 content was 3.6% w/w, i.e., 36 μg/mg P. ginseng extract) and garlic against EDTA-induced biochemical, genotoxic, and histological changes in rats. Forty male rats were divided into eight treatment groups and treated for 7 days as follows: the control group, the group treated with EDTA (20 mg/kg b.w) and the groups treated with P. ginseng extract (20 mg/kg b.w), garlic (5 mg/kg b.w), P. ginseng plus garlic alone or in combination with EDTA. In vivo bone marrow micronucleus test and random amplified polymorphism DNA-PCR (RAPD-PCR) method were performed to assess the antigenotoxic effect of both protective agents. The results indicated that EDTA administration caused a significant decrease in the serum biochemical parameters and antioxidant enzymes activity. The administration also increased lipid peroxidation and the incidence of micronucleated polychromatic erythrocytes (MnPCEs), caused appearance of some changes in polymorphism band patterns, and induced different histopathological lesions in the livers, kidneys, and testis. Treatment with P. ginseng, garlic alone or plus EDTA significantly improved all the tested parameters. Moreover, P. ginseng extract was found to be more effective than garlic in restoring the parameters that were altered by EDTA. [ABSTRACT FROM AUTHOR]

Abstract: Aflatoxins are a major risk factor for hepatocellular carcinoma (HCC), and thus understanding the pattern of aflatoxin exposure in different regions is important in order to develop targeted intervention strategies. Given the early onset of HCC in many countries early life exposures may be important. This study investigated aflatoxin exposure in Egyptian children (n =50, aged 1–2.5 years) by assessing urinary aflatoxin metabolite (AFM1, AFB1, AFB2, AFG1, AFG2) levels. Samples from Guinean children (n =50, aged 2–4 years) were analyzed in parallel providing a comparison to a region of established frequent aflatoxin exposure. Aflatoxins were isolated from urine using C18-cartridges followed by immunoaffinity clean-up, and quantified by HPLC with fluorescence detection. Overall aflatoxins were less frequently present in Egyptian (38%) than Guinean urine samples (86%) (p <0.001), which was particularly related to differences in detection rates of AFM1 (8% compared to 64%, respectively, (p <0.001)). For AFM1 the geometric mean level in Guinea (16.3pg/ml; 95% CI: 10.1, 26.6pg/ml) was 6-fold higher (p <0.001) than in Egypt (2.7pg/ml; 95% CI: 2.5, 2.8pg/ml). Urinary aflatoxins from healthy children in these two regions have not previously been reported, and exposure appears modest in Egypt compared to Guinea. These data suggest that measures to reduce aflatoxin exposure in both regions are important, though particularly in Guinea. [Copyright &y& Elsevier]

Abstract: Fumonisins (FB) are mycotoxins produced by Fusarium verticillioides, frequently associated with corn. It produces toxicity, including teratogenicity, equine leukoencephalomalacia, porcine pulmonary edema, hepatic or renal damage in most animal species and perturb sphingolipid metabolism. The aim of the present study was to evaluate the protective effects of royal jelly (RJ) against FB toxicity. Sixty male Sprague–Dawley rats were divided into six treatment groups including the control group; group fed FB-contaminated diet (200mg/kg diet) and the groups treated orally with RJ (100 or 150mg/kg body weight) with or without FB for 3 weeks. FB alone decreased body weight gain, feed intake, GPX and SOD. Whereas it increased in ALT, AST, triglycerides, cholesterol, HDL, LDL, createnine and uric acid levels. Animals received FB showed severe histological and histochemical changes in liver and kidney tissues. Cotreatment with FB plus RJ resulted in a significant improvement in all the tested parameters and the histological and histochemical pictures of the liver and kidney. These improvements were pronounced in animals fed FB-contaminated diet plus the high dose of RJ. It could be concluded that RJ have a protective effects against FB toxicity and this protection was dose dependent. [Copyright &y& Elsevier]

Abstract: Zearalenone (ZEN) is a potent estrogenic metabolite produced by some Fusarium species. No treatment has been successfully employed to remove ZEN contamination in foods. This study was conducted to evaluate the ability of hydrated sodium calcium aluminosilicate (HSCAS) to protect Balb/c mice against cytotoxicity and genotoxicity induced by ZEN. HSCAS was given via the oral route, either alone or simultaneously with a toxic intra-gastric dose of ZEN. The experimental approach comprised treatments of seven groups of mice. The first three groups received 400, 600 or 800mg/kg bw of HSCAS. Two experimental groups received, respectively, ZEN alone (40mg/kg bw, representing 8% of the LD50) and ZEN in combination with HSCAS at 400mg/kg bw. The two control groups received distilled water and olive oil, respectively. The positive control groups received colchicine (4mg/kg bw) for the micronucleus assay and mitomycin C (1mg/kg bw) for the chromosome aberration test. Forty-eight hours after treatment, the femur and tibia were dissected out and analyzed. The results show that ZEN was cytotoxic and genotoxic to Balb/c mice, as indicated by the increase in the frequencies of micronucleated polychromatic erythrocytes (PCEMN) and of chromosomal aberrations in bone-marrow cells. The simultaneous intra-gastric administration of HSCAS with ZEN resulted in a reduction in the number of PCEMN and a decrease of the chromosomal aberration frequency, and an increase in the number of polychromatic erythrocytes (PCE) in bone-marrow cells, compared with those in the group treated with ZEN alone. It could be concluded that HSCAS itself was safe and efficient in the prevention of the toxic effects of ZEN in the gastrointestinal tract. [Copyright &y& Elsevier]

• Silymarin (SIL) is a potent hepatoprotective agent but it suffers some limitation. • SIL nanoparticles (SILNPs) were prepared using chitosan nanoparticles as a delivery. • SILNPs showed smooth rounded shape with an average particle size of 100 ± 2.8 nm. • The in vitro release of SILNPs continue till 24 h however raw SIL stopped after 4 h. • SILNPs showed potential protection against CCl 4 in vivo compared to raw SIL. • ABSTRCT. This study aimed to synthesize silymarin nanoparticles (SILNPs) using chitosan nanoparticles as a delivery system and to evaluate their protective effects against CCl 4 in rats. Eight groups of male Sprague-Dawley rats were treated for three weeks included the control group, CCl 4 -treated group (100 mg/kg b.w twice a week); SIL-treated group (50 mg/lg b.w); the groups treated daily with low dose (LD) or high dose (HD) of SILNPs (25, 50 mg/kg b.w) and the groups treated with CCl 4 plus SIL, SILNPs (LD) or SILNPs (HD). Blood and tissue samples were collected for different assays. The synthesized SILNPs showed a smooth rounded shape with average particle size of 100 ± 2.8 nm. SILNPs contain the same compounds found in raw SIL and the in vitro release of SILNPs continues till 24 h. The in vivo study revealed that SIL and SILNPs at the low or high dose induced a significant improvement in the hematological parameters, liver and kidney function, lipid profile, serum cytokines, gene expression DNA fragmentation and histology of liver and kidney tissue resulted from CCl 4. It could be concluded that SILNPs can be applied in oral delivery formulations with a potential application value for liver disease therapy. [ABSTRACT FROM AUTHOR]

This study aimed to screen the bioactive components in Streptococcus equinus WC 1 (SE-WC 1 ) and Limosilactobacillus reuteri GM 4 (LR-GM 4 ) and estimate the therapeutic role in Ehrlich solid tumors (EST) mice model. Forty-four male albino EST mice were assigned into 7 groups and treated daily for 2 weeks, including the EST group, the EST mice that received SE-WC 1 at a low or a high dose (0.5 ml *10 6 or 0.5 ml *10 8  cfu), the EST mice that received LR-GM 4 at the low or the high dose (0.5 ml *10 6 or 0.5 ml *10 8  cfu), and the EST mice that received SE-WC 1 plus LR-GM 4 at the low or the high dose. Tumors were harvested, weighed, examined, and used for the determination of apoptosis-related gene expression. Samples of the intestine, liver, and kidney were gathered for histological examination. The GC-MS identified 24 and 36 bioactive compounds in SE-WC 1 and LR-GM 4 , respectively. The main compound in SE-WC 1 was lupeol; however, the main compound in LR-GM 4 was retinaldehyde. EST mice showed disturbances in Bcl-2, Bax, and p53 mRNA expression along with histological changes in the intestine, liver, and kidney. Administration of both bacterial strains reduced the tumor weight, alleviated the disturbances in the gene expression, and improved the histological structure of the intestine, liver, and kidney in a dose-dependent. Moreover, LR-GM 4 was more effective than SE-WC 1 due to its higher content of bioactive compounds. It could be concluded that these strains of probiotics are promising for the treatment of solid tumors., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Deltamethrin (DLM) is a newer kind of insecticide that is used on pets, livestock, and crops, as well as to combat malaria vectors and household pests. It belongs to the synthetic pyrethroid group and is being promoted as an alternative to organophosphate chemicals due to its persistent and destructive effects. The current study aimed to evaluate the impact of sub-chronic oral exposure to DLM on autoimmune activity in rats. Three groups of male albino rats (15 rats/group) including the control group, the ethanol-treated group (1 ml/rat), and the DLM-treated group (5 mg/kg b.w). Samples of blood were taken from all groups at 4-, 8- and 12-week intervals for the determination of hematological, cytokines, and immunological parameters. T lymphocyte subsets and Treg lymphocytes were determined in serum using flow cytometric acquisition. The results revealed that DLM significantly increased TNF-α, IL-33, IL-6, IL-17, IgG, IgM, WBCs, differential count, and platelets while decreasing Hb concentration and RBCs. Additionally, DLM decreased the number of T-cell subsets (CD3, CD4, CD5, and CD8) and Treg lymphocytes. All of these impacts became more severe over time. It is possible to conclude that the sub-chronic oral exposure to DLM disturbed autoimmune activity through the disturbances in immunological indices, CDs subset Treg lymphocytes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Childhood stunting is a global phenomenon affecting more than 149 million children under the age of 5 worldwide. Exposure to aflatoxins (AFs) in utero , during breastfeeding, and consumption of contaminated food affect the gut microbiome, resulting in intestinal dysfunction and potentially contributing to stunting. This review explores the potential relationship between AF exposure, environmental enteropathy and childhood stunting. AFs bind to DNA, disrupt protein synthesis and elicit environmental enteropathy (EE). An EE alters the structure of intestinal epithelial cells, impairs nutrient uptake and leads to malabsorption. This article proposes possible intervention strategies for researchers and policymakers to reduce AF exposure, EE and childhood stunting, such as exposure reduction, the implementation of good agricultural practices, dietary diversification and improving environmental water sanitation and hygiene.

This work was conducted to synthesize whey protein nanoparticles (WPNPs) for the coating of zinc citrate (Zn CITR) at three levels and to study their protective role against CCl 4 -induced kidney damage and inflammatory gene expression disorder in rats. Seventy male Sprague-Dawley rats were divided into seven groups and treated orally for 4 weeks as follows; the control group, the group treated twice a week with CCl 4 (5 mL/kg b.w), the groups received CCl 4 plus WPNPs (300 mg/kg b.w); the group received 50 mg/kg b.w of Zn CITR or the three formulas of Zn CITR-WPNPs at low, medium and high doses (LD, MD, and HD). Blood and kidney samples were collected for different assays and histological analyses. The fabricated particles were semispherical, with an average size of 160 ± 2.7, 180 ± 3.1, and 200 ± 2.6 nm and ζ potential of -126, -93, and -84 mV for ZN CITR-WPNPs (LD), Zn CITR-WPNPs (MD), and ZN CITR-WPNPs (HD), respectively. CCl 4 significantly increased (p ≤ 0.05) kidney function indices, oxidative stress markers, messenger RNA expression of transforming growth factor-β1, interleukin (IL)-1β, IL-10, IL-6, inducible nitric oxide synthase, and tumor necrosis factor-α and significantly decreased (p ≤ 0.05) renal superoxide dismutase, catalase, and glutathione peroxidase along with the histological changes in the kidney tissues. WPNPs, Zn CITR, and Zn CITR loaded WPNPS showed a protective effect against these complications and Zn CITR-WPNPs (LD) was more effective. WPNPs can be used effectively for coating Zn CITR at a level of 7 mg/g WPNPs to be used as a supplement for the protection of the kidney against different toxicants to enhance immunity and avoid harm of excess Zn., (© 2023 Wiley Periodicals LLC.)

This study was designed to evaluate the oxidative damage, genotoxicity, and DNA damage in the liver of rats treated with titanium nanoparticles (TiO 2 -NPs) with an average size of 28.0 nm and ξ-potential of - 33.97 mV, and to estimate the protective role of holy basil essential oil nanoemulsion (HBEON). Six groups of Male Sprague-Dawley rats were treated orally for 3 weeks as follows: the control group, HBEO or HBEON-treated groups (5 mg/kg b.w), TiO 2 -NPs-treated group (50 mg/kg b.w), and the groups treated with TiO 2 -NPs plus HBEO or HBEON. Samples of blood and tissues were collected for different analyses. The results revealed that 55 compounds were identified in HBEO, and linalool and methyl chavicol were the major compounds (53.9%, 12.63%, respectively). HBEON were semi-round with the average size and ζ-potential of 120 ± 4.5 nm and - 28 ± 1.3 mV, respectively. TiO 2 -NP administration increased the serum biochemical indices, oxidative stress markers, serum cytokines, DNA fragmentation, and DNA breakages; decreased the antioxidant enzymes; and induced histological alterations in the liver. Co-administration of TiO 2 -NPs plus HBEO or HBEON improved all the tested parameters and the liver histology, and HBEON was more effective than HBEO. Therefore, HEBON is a promising candidate able to protect against oxidative damage, disturbances in biochemical markers, gene expression, DNA damage, and histological changes resulting from exposure to TiO 2 -NPs and may be applicable in the food and pharmaceutical sectors., (© 2022. The Author(s).)

Background: Titanium dioxide nanoparticles (TiO 2 -NPs) are widely utilized in medicine and industry; however, their safety in biological organisms is still unclear. In this study, we determined the bioactive constitutes of thyme essential oil (TEO) and utilized the nanoemulsion technique to improve its protective efficiency against oxidative stress, genotoxicity, and DNA damage of biosynthesized titanium dioxide nanoparticles (TiO 2 -NPs)., Methods: TEO nanoemulsion (TEON) was prepared using whey protein isolate (WPI). Sixty male Sprague-Dawley rats were divided into six groups and treated orally for 21 days including the control group, TEO, or TEON- treated groups (5 mg/kg b.w), TiO 2 -NPs-treated group (50 mg/kg b.w) and the groups received TiO 2 -NPs plus TEO or TEON. Blood and tissues samples were collected for different assays., Results: The GC-MS analysis identified 17 bioactive compounds in TEO and thymol and carvacrol were the major compounds. TEON was irregular with average particles size of 230 ± 3.7 nm and ζ-potential of -24.17 mV. However, TiO2-NPs showed a polygonal shape with an average size of 50 ± 2.4 nm and ζ-potential of -30.44 mV. Animals that received TiO2-NPs showed severe disturbances in liver and kidney indices, lipid profile, oxidant/antioxidant indices, inflammatory cytokines, gene expressions, increased DNA damage, and pathological changes in hepatic tissue. Both TEO and TEON showed potential protection against these hazards and TEON was more effective than TEO., Conclusion: The nanoemulsion of TEO enhances the oil bioactivity, improves its antioxidant characteristics, and protects against oxidative damage and genotoxicity of TiO2-NPs., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Background: Zinc (Zn) is an essential trace element required for the function of the immune system. However, Zn fortification of food has faced some challenges, although excess Zn may be induced obesity and other related. This study aimed to use Zn-loaded whey protein nanoparticles (Zn-WPNPs) to enhance the immunomodulatory activity of Zn in rats treated with CCl 4 ., Methods: Zn was loaded to WPNPs at a level of 14 mg/g. Four experimental groups of male albino Wistar rats were treated for 30 days including the control group, CCl 4 -treated group (0.5 ml/100 g b.w), Zn plus CCl 4 -treated group (50 mg/kg b.w), and CCl 4 plus Zn-WPNPs-treated group (50 mg/kg b.w). Blood and tissue samples were collected for different assays and histological examinations., Results: The results revealed that CCl 4 disturbs the serum biochemical, hematological, and immune indicators in different organs besides the liver as a target organ. Animals that received CCl 4 showed a significant increase in oxidative stress markers, cytokines, and the mRNA expression of inflammatory mediators in the lung and spleen accompanied by a significant decrease in the hepatic and renal antioxidant enzymes along with histological changes in the liver, kidney, spleen, and lung. Zn or Zn-WPNPs could improve these parameters and the histological picture of the tested organs and Zn-WPNPs were more effective than Zn alone., Conclusion: WPNPs induced synergistic immune-modulating effects which may control Zn release and may be a suitable candidate to enhance the immune system during any pandemic or the exposure to any chemicals that affect the immune system., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin that induces severe health disturbances in humans and animals. This study aimed to determine the bioactive compounds in Costus speciosus extract (CSE) using GC-MS and evaluate its protective capability against ZEN-induced oxidative damage, genotoxicity, and cytotoxicity in rats. Six groups of male Sprague Dawley rats were treated orally for 15 days including the control group, CSE-treated groups at low (200 mg/kg b. w) or high (400 mg/kg b. w) dose, ZEN-treated group (40 μg/kg b. w), and the groups treated with ZEN plus the low or the high dose of CSE. Blood and tissue samples were collected for different assays and pathological analyses. The results of GC-MS indicated the identification of 6 compounds and Azulene was the major. Animals that received ZEN showed severe disturbances in serum biochemical, cytokines, oxidative stress indicators, mRNA expression of iNOS, Nrf2, and inflammatory-related genes. ZEN also increased micronucleated polychromatic erythrocytes (MNPCEs) and comet tail formation in bone marrow cells along with the disturbances in the histological architecture of the liver and kidney. Co-administration of CSE plus ZEN could normalize the majority of the tested parameters and the histological picture at a dose as low as 200 mg/kg b. w. Therefore, CSE protects against ZEN toxicity via its antioxidant activity, modulation of iNOS, inflammatory-related genes, and the Nrf2 pathway and it could be used in the endemic regions., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Solid tumors are fairly common and face many clinical difficulties since they are hardly surgically resectable and broadly do not respond to radiation and chemotherapy. The current study aimed to fabricate ginsenoside Rg3 nanoparticles (Rg3-NPs) and evaluate their antitumor effect against Ehrlich solid tumors (EST) in mice. Rg3-NPs were fabricated using whey protein isolates (WPI), maltodextrin (MD), and gum Arabic (GA). EST was developed by the injection of mice with Ehrlich ascites cells (2.5 × 10 6 ). The mice were divided into a control group, EST group, and the EST groups that were treated orally 2 weeks for with normal Rg3 (3 mg/kg b.w.), Rg3-NPs at a low dose (3 mg/kg b.w.), and Rg3-NPs at a high dose (6 mg/kg b.w.). Serum and solid tumors were collected for different assays. The results revealed that synthesized Rg3-NPs showed a spherical shape with an average particle size of 20 nm and zeta potential of -5.58 mV. The in vivo study revealed that EST mice showed a significant increase in AFP, Casp3, TNF-α, MMP-9, VEGF, MDA, and DNA damage accompanied by a significant decrease in SOD and GPx. Treatment with Rg3 or Rg3-NPs decreased the tumor weight and size and induced a significant improvement in all the biochemical parameters. Rg3-NPs were more effective than Rg3, and the improvement was dose-dependent. It could be concluded that fabrication of Rg3-NPs enhanced the protective effect against EST development which may be due to the synergistic effect of Rg3 and MD, GA, and WPI., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study was conducted to identify the bioactive phytochemicals in Salvia officinalis essential oil, to determine the polyphenols in the aqueous extract (SOE), and to evaluate their protective role against cadmium (Cd)-induced oxidative damage and genotoxicity in rats. Six groups of female rats were treated orally for 2 weeks including the control group, CdCl 2 -treated group, SOE-treated groups at low or high dose (100 and 200 mg/kg b.w), and CdCl 2 plus SOE-treated groups at the two doses. The GC-MS analysis identified 39 compounds; the main compounds were 9-octadecenamide, eucalyptol, palmitic acid, and oleic acid. However, the HPLC analysis showed 12 polyphenolic compounds and the majority were coumaric acid, chlorogenic acid, coffeic acid, catechin, vanillin, gallic acid, ellagic acid, and rutin. In the biological study, rats received CdCl 2 displayed severe disturbances in liver and kidney indices alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (Alb), total protein (TP), total bilirubin (T. Bil), direct bilirubin (D. Bil), creatinine, uric acid, and urea, lipid profile, tumor necrosis factor-alpha (TNF-α), alpha-fetoprotein (AFP) and CEA), glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT), malondialdehyde (MDA), nitric oxide (NO), gene expressions, DNA fragmentation, and histological alterations in the liver and kidney tissue. SOE showed a potent antioxidant and mitigated these alterations in serum and tissue. Moreover, the high dose succeeded to normalize most of the tested parameters and histological features. It could be concluded that S. officinalis is a promising source for bioactive compounds with therapeutic benefits against environmental toxicants., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Fish oil exhibited several beneficial effects on human health; however, its applications face several challenges such as its effects on the organoleptic properties of food and its susceptibility to oxidation. Titanium dioxide NPs (TiO 2 -NPs) are utilized widely in pharmaceutical and food applications although there are some reports about their oxidative damage to living organisms. The current work was undertaken to identify fatty acids content in mullet fish oil, encapsulation, and characterization of the oil, and to assess the protective efficiency of the encapsulated mullet fish oil (EMFO) against the oxidative damage and genotoxicity of TiO 2 -NPs in rats. Sixty female Sprague-Dawley rats were distributed to 6 groups and treated for 21 days included the control group; TiO 2 -NPs-treated group (50 mg/kg b.w); the groups treated with EMFO (50 or 100 mg/kg b.w) and the groups received TiO 2 -NPs plus EMFO at the low or high dose. Samples of blood, liver, and kidney were taken for different assays and histological studies. The GC-FID analysis showed that a total of 14 different fatty acids were found in Mullet fish oil included 41.4% polyunsaturated fatty acids (PUFAs), 31.1% monounsaturated fatty acids (MUFAs), and 25.1% saturated fatty acids (SFAs). The structure of EMFO was spherical with an average diameter of 234.5 nm and a zeta potential of -6.24 mV and was stable up to 10 days at 25 °C with EE of 81.08%. The PV of EMFO was decreased at 5 days then increased at 15 days; however, TBARS was increased throughout the storage time over 15 days. The biological evaluation showed that TiO 2 -NPs disturb the hepato-nephro functions, lipid profile, inflammatory cytokines, oxidative stress markers, antioxidant enzymes activity, and their corresponding gene expression along with severe pathological alterations in both hepatic and renal tissue. Co-administration of EMFO induced a strong antioxidant role, and the high level could normalize the majority of the parameters tested and the histological picture of the hepatic and renal tissues. These results pointed out that the encapsulation technology enhances the protective role of EMFO against oxidative stress and genotoxicity of TiO 2 -NPs through the prevention of ω-3 PUFAs oxidation and controlling their release., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors.)

The green synthesis of metal nanoparticles is growing dramatically; however, the toxicity of these biosynthesized particles against living organisms is not fully explored. Therefore, this study was designed to synthesize and characterize TiO 2 -NPs, encapsulation and characterization thyme essential oil (ETEO), and determination of the bioactive constituents of ETEO using GC-MS and evaluate their protective role against TiO 2 -NPs-induced oxidative damage and genotoxicity in rats. Six groups of rats were treated orally for 30 days including the control group, TiO 2 -NPs (300 mg/kg b.w)-treated group, ETEO at low (50 mg/kg b.w) or high dose (100 mg/kg b.w)-treated groups, and TiO 2 -NPs plus ETEO at the two doses-treated groups. Blood and tissues were collected for different assays. The GC-MS results indicated the presence of 21 compounds belonging to phenols, terpene derivatives, and heterocyclic compounds. The synthesized TiO 2 -NPs were 45 nm tetragonal particles with a zeta potential of -27.34 mV; however, ETEO were 119 nm round particles with a zeta potential of -28.33 mV. TiO 2 -NPs administration disturbs the liver and kidney markers, lipid profile, cytokines, oxidative stress parameters, the apoptotic and antioxidant hepatic mRNA expression, and induced histological alterations in the liver and kidney tissues. ETEO could improve all these parameters in a dose-dependent manner. It could be concluded that ETEO is a promising candidate for the protection against TiO 2 -NPs and can be applied safely in food applications., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Although the green synthesis of nanometals is eco-friendly, the toxicity or safety of these biosynthesized nanoparticles in living organisms is not fully studied. This study aimed to evaluate the potential protective role of encapsulated thyme oil (ETO) against zinc oxide nanoparticles (ZnO-NPs). ETO was prepared using a mixture of whey protein isolate, maltodextrin, and gum Arabic, and ZnO-NPs were synthesized using parsley extract. Six groups of male Sprague-Dawley rats were treated orally for 21 days which included the control group, ZnO-NP-treated group (25 mg/kg body weight (b.w.)), ETO-treated groups at low or high dose (50, 100 mg/kg b.w.), and the groups that received ZnO-NPs plus ETO at the two tested doses. Blood and tissue samples were collected for different assays. The results showed that carvacrol and thymol were the major components in ETO among 13 compounds isolated by GC-MS. ZnO-NPs were nearly spherical and ETOs were round in shape with an average size of 38 and 311.8 nm, respectively. Administration of ZnO-NPs induced oxidative stress, DNA damage, biochemical, ctyogentical, and histological changes in rats. ETO at the tested doses alleviated these disturbances and showed protective effects against the hazards of ZnO-NPs. It could be concluded that encapsulation of thyme oil using whey protein isolate, maltodextrin, and gum Arabic improved the antioxidant properties of ETO, probably possess synergistic effects, and can be used as a promising tool in pharmaceutical and food applications., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Mycorrhizal symbiosis is generally considered effective in ameliorating plant tolerance to abiotic stress by altering gene expression, and evaluation of genes involved in ion homeostasis and nutrient uptake. This study aimed to use arbuscular mycorrhizal fungus (AMF) to alleviate salinity stress and analyse relevant gene expression in pistachio plants under No/NaCl stress in greenhouse conditions. Arbuscular mycorrhizal symbiosis was used to study the physiological responses, ion distribution and relevant gene expression in pistachio plants under salinity stress. After four months of symbiosis, mycorrhizal root colonization showed a significant reduction in all tested parameters under salt stress treatment compared to non-saline treatment. Salinity affected the morphological traits, and decreased the nutrient content including N, P, Mg and Fe as well as K/Na and Ca/Na ratios, relative water content (RWC), membrane stability index (MSI), and increased the concentration of K, Ca and Na nutrient, glycine betaine, ROS and MDA. Inoculation of seedlings with AMF mitigated the negative effects of salinity on plant growth as indicated by increasing the root colonization, morphological traits, glycine betaine, RWC and MSI. Specifically, under salinity stress, shoot and root dry weight, P and Fe nutrient content, K/Na and Ca/Na ratio of AMF plants were increased by 53.2, 48.6, 71.6, 60.2, 87.5, and 80.1% respectively, in contrast to those of the NMF plants. The contents of Na, O 2•- and MDA in AMF plants were significantly decreased by 66.8, 36.8, and 23.1%, respectively at 250 mM NaCl. Moreover, salinity markedly increased SOS1, CCX2 and SKOR genes expression and the inoculation with AMF modulated these genes expression; however, NRT2.4, PHO1 and PIP2.4 gene expressions were increased by salinity and AMF. It could be concluded that inoculation of AMF with Rhizophagus irregularis conferred a larger endurance towards soil salinity in pistachio plants and stimulate the nutrient uptake and ionic homeostasis maintenance, superior RWC and osmoprotection, toxic ion partitioning, maintaining membrane integrity and the ion-relevant genes expression., Competing Interests: Conflicts of interestThe authors declare that they have no conflict of interest., (© Prof. H.S. Srivastava Foundation for Science and Society 2021.)

Recently, bio-nanofabrication becomes one of the widest methods for synthesizing nanoparticles (NPs); however, there is scanty literature exploring the toxicity of these green NPs against living organisms. This study aimed to evaluate the potential protective role of encapsulated cinnamon oil (ECO) against titanium oxide nanoparticle (TiO 2 NP)-induced oxidative stress, DNA damage, chromosomal aberration, and reproductive disturbances in male mice. Sixty male Balb/c mice were distributed into six groups treated orally for 3 weeks and included control group, TiO 2 NP-treated group (25 mg/kg b.w), ECO at low or high dose-treated groups (50 or 100 mg/kg b.w), and the groups that received TiO 2 NPs plus ECO at a low or high dose. The results of GC-MS revealed the isolation of 21 compounds and the majority was cinnamaldehyde. The average size zeta potential of TiO 2 NPs and ECO were 28.9 and 321 nm and -33.97 and -17.35 mV, respectively. TiO 2 NP administration induced significant changes in liver and kidney function, decreased antioxidant capacity, and increased oxidative stress markers in liver and kidney, DNA damage in the hepatocytes, the number of chromosomal aberrations in the bone marrow and germ cells, and sperm abnormalities along with histological changes in the liver, kidney, and testis. Co-administration of TiO 2 NPs and ECO could alleviate these disturbances in a dose-dependent manner. It could be concluded that ECO is a promising and safe candidate for the protection against the health hazards of TiO 2 NPs., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The application of essential oils in food and pharmaceutical sectors face several challenges due to their sensitivity to oxidation process. Additionally, the biosynthesis of nanometals is growing rapidly; however, the toxicity of these particles against living organisms did not well explore yet. This study aimed to determine the bioactive compounds in basil essential oil (BEO) using GC-MS, to encapsulate and characterize BEO and to evaluate its protective role against the oxidative stress and genotoxicity of biosynthesized iron nanoparticles (Fe-NPs) in rats. Six groups of male Sprague-Dawley rats were treated orally for 4 weeks included the control group, Fe-NPs-treated group (100 mg/kg b.w.); EBEO-treated groups at low (100 mg/kg b.w.) or high (200 mg/kg b.w.) dose and the groups treated with Fe-NPs plus the low or the high dose of EBEO. The GC-MS analysis revealed the identification of 48 compounds and linalool was the major compound. The average sizes and zeta potential of the synthesized Fe-NPs and EBEO were 60 ± 4.76 and 120 ± 3.2 nm and 42.42 mV and -6.4 mV, respectively. Animals treated with Fe-NPs showed significant increase in serum biochemical analysis, oxidative stress markers, cytokines, lipid profile, DNA fragmentation and antioxidant enzymes and their gene expression and severe changes in the histology of liver and kidney tissues. Administration of Fe-NPs plus EBEO alleviated these disturbances and the high dose could normalize most of the tested parameters and improved the histology of liver and kidney. It could be concluded that caution should be taken in using the biosynthesized metal nanoparticles in different application. EBEO is a potent candidate to protect against the hazards of metal nanoparticles and can be applied in food and medical applications., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors.)

Pyrethroids are synthetic chemicals similar to the pyrethrins, but more toxic to insects and mammals and persistent in the environment than pyrethrins. This study aimed to identify the bioactive compounds of Amphora coffeaeformis extract (ACE) and to determine their potential protective activity against deltamtherin (DEL) insecticide in rats. Six groups of male albino rats were treated for 4 weeks included the control group, ACE-treated group (772 mg/kg b.w.), DEL-exposed group (13.5 mg/kg b.w.), DEL plus ACE-treated group, and the groups treated with ACE for 14 days before or after DEL. At the end of treatment, blood and tissue samples were collected for biochemical assays. The GC-MS identified 18 compounds; most of them are fatty acid methyl ester, and the HPLC identified 8 polyphenols and significant amounts of vitamins A, C, B1, B2, B9, and E. The in vivo results revealed that DEL induced significant alterations in hematological and serum biochemical parameters, oxidative stress markers, proinflammatory cytokines, and NF-κB. ACE protects against DEL toxicity, and the protection was more pronounced in the groups treated with ACE plus DEL or ACE after DEL suggesting that ACE could be used for the prevention or the treatment of DEL toxicity. It could be concluded that ACE is a promising candidate for the production of bioactive compounds and should be considered in the pharmaceutical and food application.

This study aimed to identify the bioactive compounds of the ethyl acetate extract of Aspergillus niger SH2-EGY using GC-MS and to evaluate their protective role against aflatoxin B 1 (AFB 1 )-induced oxidative stress, genotoxicity and cytotoxicity in rats. Six groups of male Sprague-Dawley rats were treated orally for 4 weeks included the control group, AFB 1 -treated group (80 μg/kg b.w); fungal extract (FE)-treated groups at low (140) or high dose (280) mg/kg b.w and the groups treated with AFB 1 plus FE at the two tested doses. The GC-MS analysis identified 26 compounds. The major compounds found were 1,2,3,4,6-Penta-trimethylsilyl Glucopyranose, Fmoc-L-3-(2-Naphthyl)-alanine, D-(-)-Fructopyranose, pentakis (trimethylsilyl) ether, bis (2-ethylhexyl) phthalate, trimethylsilyl ether-glucitol, and octadecanamide, N-(2- methylpropyl)-N-nitroso. The in vivo results showed that AFB 1 significantly increased serum ALT, AST, creatinine, uric acid, urea, cholesterol, triglycerides, LDL, carcinoembryonic antigen, alpha-fetoprotein, interleukin-6, Malondialdehyde, nitric oxide, Bax, caspase-3 and P53 mRNA expression, chromosomal aberrations and DNA fragmentation. It decreased serum TP, albumin, HDL, Bcl-2 mRNA expression, hepatic and renal TAC, SOD and GPx content and induced histological changes in the liver and kidney. FE prevented these disturbances in a dosage-dependent manner. It could be concluded that A. niger SH2-EGY extract is safe a promising agent for pharmaceutical and food industries., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

This study aimed to determine the bioactive compounds of Bacillus sp. MERNA97 extract and to evaluate their efficacy against the oxidative damage, genotoxicity, chromosomal aberration and DNA fragmentation in rats treated with AFB 1 . Sixty male Sprague-Dawley rats were divided into 6 groups and treated for 6 weeks and included the control group, AFB 1 -treated group (80 μg/kg b. w), the groups treated with Bacillus extract (BE) at low (2 mg/kg b.w) or high (4 mg/kg b.w) dose and the groups treated with AFB 1 plus BE at the two doses. Blood and tissues samples were collected for different assays. The GC-MS results revealed the isolation of 44 compounds belong to different classes. The in vivo results showed that AFB 1 disturbs all the biochemical parameters, oxidative stress markers, cytokines gene expression chromosomal aberration and DNA fragmentation along with the histological changes in the liver tissue. BE at the two tested doses induced a significant improvement in all parameters tested and the histological picture in a dose dependent manner. It could be concluded that the extract of Bacillus sp. MERNA97 isolated from the marine environment in the Red Sea is a promise as a source of novel compounds with therapeutically benefits., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

This study aimed to evaluate the protective role of encapsulated cinnamon oil emulsion (COE) in whey protein concentrate (WPC) against the disturbance in lipid profile, oxidative stress markers, and gene expression in streptozotocin (STZ)-treated rats. COE was analyzed using GC-MS, and the emulsion was prepared and characterized. In the in vivo study, six groups of male rats were treated orally for 4 weeks, including the control group, the group treated with STZ (D-rats), the groups received a low or high dose of COE (200 or 400 mg/kg B.w.), and the D-rats groups received COE at the low or high dose. Blood and tissue samples were collected after the end of the treatment period for biochemical, genetical, and histological analyses. The GC-MS results revealed that the major components of the oil were cinnamaldehyde, 1,8 cineole, acetic acid, 1,7,7-trimethylbicyclo[2.2.1]hept2yl ester, α-Pinene, and α-Terpineol. The size, zeta potential, and polydispersity index (PDI) of COE were 240 ± 1.03 nm, - 7.09 ± 0.42, and 0.36, respectively. The in vivo results revealed that COE at the two tested doses improved the levels of glucose, insulin, amylase, lipid profile, hepatic MDA, SOD, and GSH. COE also downregulated hepatic GLU2, FAS, SREBP-1c, and PEPCK gene expression and upregulated IGF-1 mRNA expression in diabetic rats in a dose-dependent manner. Moreover, COE improved and the histological picture of the liver and pancreas. It could be concluded that COE overcomes the disturbances in biochemical, cytological, and histopathological changes in D-rats via the enhancement of antioxidant capacity; reduces the oxidative stress; modulates the concerned gene expression; and may be promising to develop new drugs for diabetic treatment.

Background: Diamond nanoparticles (Nanodiamond) are biocompatible drug delivery platforms with outstanding surface properties. Their passage into the brain has been confirmed previously. Thus, nanodiamond could provide a drug delivery system to shuttle several drugs through the blood-brain barrier (BBB) which represents a real challenge for the effective delivery of several drugs into the brain. Amlodipine is a calcium channel blocker that cannot pass through BBB and may elicit neuroprotective effects to reverse calcium-induced excitotoxicity and mitochondrial dysfunction that underlie several neurologic disorders including Alzheimer's disease and stroke., Aim: The study aimed to investigate the loading of amlodipine on nanodiamond particles., Methods: Nanodiamond particles were oxidized in a strong oxidizing acidic mixture of sulfuric and nitric acids. Adsorption of amlodipine on nanodiamond particles was achieved in alkaline pH using various concentrations of sodium hydroxide. The loaded amlodipine was determined by high-performance liquid chromatography and confirmed by Fourier transform infrared (FTIR) spectroscopy and transmission electron microscopy., Results: The highest percentage (41%) of loaded amlodipine onto nanodiamond particles was achieved in alkaline medium using 2 mM NaOH at a corresponding pH of 8.5. Also, characteristic FTIR bands of amlodipine and nanodiamond were shown obviously in the nanodiamond-amlodipine conjugates. Moreover, the successful loading of amlodipine on diamond nanoparticles was confirmed by transmission electron microscopy., Conclusion: The present study demonstrates the successful loading of amlodipine onto nanodiamond particles. These findings offer a potential for applying diamond nanoparticles as a drug delivery system to shuttle amlodipine into the brain and open the door to deliver other similar drugs into the brain., Competing Interests: The authors declare that there are no conflicts of interest in this work., (© 2019 Alawdi et al.)

The aims of this study were to determine the polyphone content of grape seed extract (GSE) and to assess their protective effects against zearalenone (ZEN)-induced maternal toxicity and in utero development defects in mice. Five groups of pregnant mice were treated orally during days 6-13 of gestation as follows: control group, corn oil as vehicle (0.1 ml/mice)-treated group, ZEN-treated group (25 mg/kg b.w), GSE-treated group (150 mg/kg b.w.), and ZEN plus GSE-treated group. All animals were sacrificed on the 19th day of gestation and samples of bone marrow were collected for the micronucleus assay. The maternal and developmental toxicity were carried out. The HPLC analyses revealed that GES is rich in gallic acid, syringic acid, vanillin, quercetin, and coumaric acid. ZEN administration resulted in severe maternal and developmental toxicity which included an increase of micronuclei formation in bone marrow, decreased maternal weight gain, and litter weight. It also induces fetal growth retardation, increased number of the aborted dams and resorbed fetuses, abnormality of fetal bone ossification, and number of fetuses with a hematoma. GSE showed positive effects on the pregnant mice and the developing fetuses. Moreover, it counteracted the detrimental effects of ZEN in dams and fetuses. It could be concluded that polyphenols in GSE are a promising candidate to protect against ZEN toxicity in highly endemic areas.

Fumonisin B 1 (FB 1 ) and aflatoxin B 1 (AFB 1 ) are fungal metabolites that frequently co-occur in foodstuffs and are responsible for mycotoxicosis and several primary cancers. Cinnamon essential oil (CEO) has a spacious range of benefit effects but also has some limitations owing to its strong taste or its interaction with some drugs. This study aimed to use the cinnamon oil emulsion droplets (COED) for the protection against oxidative stress, cytotoxicity, and reproductive toxicity in male Sprague-Dawley rats sub-chronically exposed to FB 1 and/or AFB 1 . The composition of CEO was identified using GC-MS then was encapsulated using whey protein as wall material. Male rats were divided into eight groups and treated orally for 8 weeks as follows: control group, AFB 1 -trreated group (80 μg/kg b.w), FB 1 -treated group (100 mg/kg b.w), FB 1 plus AFB 1 -treated group, and the groups treated with COED plus FB 1 and/or AFB 1 . Blood and samples of the kidney, liver, and testis were collected for different analysis and histopathological examination. The GC-MS analysis revealed that cinnamaldehyde, α-copaene, trans-cinnamaldehyde, caryophyllene, and delta-cadinene were the main compounds in COE. The average size of COED was 235 ± 1.4 nm and the zeta potential was - 6.24 ± 0.56. Treatment with FB 1 and/or AFB 1 induced significant disturbances in the serum biochemical analysis, oxidative stress parameters, DNA fragmentation, gene expression, and testosterone and severe pathological changes in the tested organs. Moreover, treatment with both mycotoxins induced synergistic toxic effects. COED did not induce toxic effects and could normalize the majority of the tested parameters and improve the histological picture in rats treated with FB 1 and/or AFB 1 . It could be concluded that COED induce potential protective effects against the single or combined exposure to FB 1 and AFB 1 .

Deoxynivalenol (DON) is a Fusarium mycotoxin that frequently contaminates cereal and cereal-based food and induces liver injury. This study evaluated the protective role of silymarin nanoparticles (SILNPs) and inulin nanoparticles (INNPs) against DON-induced liver injury in rats. Eleven groups of rats were treated orally for 3 weeks as follows: the control group, DON-treated group (5 mg/kg b.w.); INNPs-treated groups at low (LD) or high (HD) dose (100 or 200 mg/kg b.w.); SILPNs-treated group (50 mg/kg b.w.); SILNPs plus INNPs(LD) or INNPs(HD)-treated groups; INNPs(LD) or INNPs(HD) plus DON-treated groups and DON plus SILNPs and INNPs(LD) or INNPs(HD)-treated groups. Blood and tissue samples were collected for different analyses. The results revealed that the practical sizes were 200 and 98 nm for SILNPs and INNPs respectively. DON increased liver enzymes activity, lipid profile, serum cytokines, number and percentage of chromosomal aberration, DNA fragmentation and comet score. It disturbed the oxidative stress markers, down regulated gene expression and induced histological changes in the liver tissue. Treatment with DON and SILNPs and/or INNPs at the two tested doses improved all the tested parameters and SILNPs plus INNPs(HD) normalized most of these parameters in DON-treated animals. SILNPs and INNPs could be promising candidates as hepatoprotective against DON or other hepatotoxins., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Fusarium mycotoxins are nature environmental contaminants worldwide in animal feed and human food resulting in a serious health risk. The present study aimed to evaluate the potential role of organo-modified nano-montmorillonite (OMNM) against the health risk and the oxidative stress resulted from the exposure of fumonisin (FB 1 ) and zearalenone (ZEN) individually and in combination in rats. Eight groups of female Sprague Dawley rats were treated orally for 3 weeks including the control group, FB 1 alone-treated group (50 mg/kg b.w.), ZEN alone-treated group (40 μg/kg b.w), FB 1 plus ZEN-treated group, the group fed basal diet supplemented with OMNM (5 g/kg diet), and the groups fed basal diet supplemented with OMNM and treated with FB 1 and/or ZEN. At the end of the experimental period, samples of blood and tissues were collected for different biochemical and histological analyses. The results revealed that administration of FB 1 and/or ZEN resulted in significant disturbances in the biochemical parameters tested, lipid profiles, serum cytokines, oxidative stress indices, the activity of antioxidant enzymes, and the histological status of the liver and kidney. Co-administration of both mycotoxins indicated a synergistic effect. OMNM alone was safe and succeeded to reduce and/or prevent most of the toxicity of both mycotoxins. It could be concluded that OMNM is a novel and promising nanograde adsorbent suitable for the protection against the combined exposure to FB 1 and ZEN.

Current therapeutic approaches of Alzheimer's disease (AD) are symptomatic and of modest efficacy, and there is no available effective cure or prevention of AD; hence, the need arise to search for neuroprotective agents to combat AD. The current study aimed at investigating the neuroprotective effect of nanodiamond (ND), adamantine-based nanoparticles, in aluminum-induced cognitive impairment in rats, an experimental model of AD. AD was induced by aluminum chloride (17 mg/kg, p.o. for 6 weeks) and confirmed by Morris water maze and Y-maze behavioral tests. Biochemical and histological analyses of the hippocampus were also performed. Aluminum-treated rats showed behavioral, biochemical, and histological changes similar to those associated with AD. ND improved learning and memory and reversed histological alterations. At the molecular levels, ND mitigated the increase of hippocampal beta-amyloid (Aβ 42 ) and beta-site amyloid precursor protein cleaving enzyme-1 (BACE1) together with down-regulation of phosphorylated tau protein. It also modulated the excitatory glutamate neurotransmitter level. Furthermore, ND boosted the brain-derived neurotrophic factor (BDNF) and mitochondrial transcription factor-A (TFAM), suppressed the proinflammatory cytokine tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and curbed oxidative stress by hampering of inducible nitric oxide synthase (iNOS). Moreover, ND augmented the hippocampal levels of phosphorylated signal transducer and activator of transcription-3 (p-STAT3) and B cell leukemia/lymphoma-2 (Bcl-2) anti-apoptotic protein while diminished nuclear factor-kappaB (NF-κB) and caspase-3 (casp-3) expression. These findings indicate the protective effect of ND against memory deficits and AD-like pathological aberrations probably via modulating NF-kB and STAT3 signaling, effects mediated likely by modulating N-methyl-D-aspartate (NMDA) receptors.

This study aimed to evaluate the protective role of chitosan nanoparticles (COS-NPs) singly or plus quercetin (Q) against OTA-induced oxidative stress and renal genotoxicity. Twelve groups of male Sprague-Dawley rats were treated orally for 3 weeks included the control group, animals fed OTA-contaminated diet (3 mg/kg diet); COS-NPs-treated groups at low (140 mg/kg b.w.) or high (280 mg/kg b.w.) dose, Q-treated group (50 mg/kg b.w.), Q plus low or high dose of COS-NPs-treated groups and OTA plus Q and/or COS-NPs at the two tested doses-treated groups. The results indicated that COS-NPs were roughly rod in shape with average particle size of 200 nm and zeta potential 31.4 ± 2.8 mV. Animals fed OTA-contaminated diet showed significant changes in serum biochemical parameters, increase kidney MDA and DNA fragmentation and decreased GPx and SOD gene expression accompanied with severe histological changes. Q and/or COS-NPs at the two tested doses induced significant improvements in all tested parameters and succeeded to overcome these effects especially in the animals treated with Q plus the high dose of COS-NPs. It could be concluded that COS-NPs are promise candidate to enhance the antioxidant effect of Q and protect against the nephrotoxicity of OTA in high endemic areas., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The current study aimed to evaluate the protective role of curcumin nanoparticles loaded hydrogels (Cur-NPs-Hgs) against AFB1-induced genotoxicity in rat liver. Animals were divided into 7 treatment groups and treated orally for 3 weeks as follow: the control group, the group treated with Hgs alone (0.5 ml/rat), the groups treated with low or high dose of Cur-NPs-Hgs (100 or 200 mg/kg b.w), the group treated with AFB1 (0.125 mg/kg b.w) and the groups treated with AFB1 plus the low or high dose of Cur-NPs-Hgs. Blood ant liver samples were collected for different biochemical, genetical, histological and histochemical analysis. The results revealed that the prepared Cur-NPs have nearly spherical shape with average size of 140 ± 20 nm and negative zeta potential value of 30.7 ± 2.57 mV. The in vivo results showed that treatment with AFB1 decreased the body weight accompanied biochemical, genotoxicity and histological disturbances. The combined treatment with AFB1 and Cur-Nps-Hgs at the two tested doses succeeded to induce a significant protection against AFB1. It could be concluded that Cur-NPs-Hgs is a promise candidate to protect against AFB1-induce liver damage in the high incidence area. Moreover, Hgs are excellent candidates as drug delivery system., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Aflatoxins and fumonisins are important food-borne mycotoxins implicated in human health and have cytotoxic effects. The aims of the current study were to evaluate the protective role of Panax ginseng extract (PGE) against the synergistic effect of subchronic administration of aflatoxin B1 (AFB1) and fumonisin B1 (FB1) on DNA and gene expression in rat. Female Sprague-Dawley rats were divided into eight groups (ten rats/group) and treated for 12 weeks including the control group, the group having received AFB1 (80 µg/kg bw), the group having received FB1 (100 µg/kg bw), the group having received AFB1 plus FB1 and the groups having received PGE (20 mg/kg bw) alone or with AFB1 and/or FB1. At the end of experiment, liver and kidney were collected for the determination of DNA fragmentation, lipid peroxidation (LP), glutathione (GSH) contents and alterations in gene expression. The results indicated that these mycotoxins increased DNA fragmentation, LP and decreased GSH content in liver and kidney and down-regulated gene expression of antioxidants enzymes. The combined treatments with AFB1 and/or FB1 plus PGE suppressed DNA fragmentation only in the liver, normalized LP and increased GSH in the liver and kidney as well as up-regulated the expression of GPx, SOD1 and CAT mRNA. It could be concluded that AFB1 and FB1 have synergistic genotoxic effects. PGE induced protective effects against their oxidative stress and genotoxicity through its antioxidant properties.

This study was conducted to prepare and characterize activated carbon (AC) and to evaluate its protective effect against deoxynivalenol (DON) toxicity in rats compared to Egyptian montmorillonite (EM). AC was prepared using a single-step chemical activation with phosphoric acid (H3PO4). The resulted AC has a high surface area and a high total pore volume. Male Sprague-Dawley rats were divided into 6 groups (n = 10) and treated for 3 weeks as follow: the control group, the groups fed AC or EM-supplemented diet (0.5% w/w), the group treated orally with DON (5 mg/kg b.w.) and the groups fed AC or EM-supplemented diet and treated with DON. Blood and liver samples were collected for different analyses. Treatment with DON increased liver function enzymes, lipid peroxidation, tumor necrosis factor α, DNA fragmentation, decreased hepatic glutathione content, up regulating mRNA Fas and TNF-α genes expression and increased micronucleated polychromatic erythrocytes and normochromatic erythrocytes in bone marrow. Co-treatment of DON plus AC or EM succeeded to normalize the levels of the biochemical parameters, reduced the cytotoxicity of bone marrow and ameliorated the hepatic genotoxicity. Moreover, AC was more effective than EM and has a high affinity to adsorb DON and to reduce its cytotoxicity and genotoxicity., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

This study was conducted to evaluate the protective role of quercetin (Q) against the cytotoxicity, DNA damage and oxidative stress in rats fed aflatoxin (AFs)-contaminated diet. Female Sprague-Dawley rats were divided into six groups and treated for 21 days as follows: the control group; the group fed AFs-contaminated diet (1.4 mg/kg diet); the groups treated orally with Q at low or high dose (50 and 100 mg/kg b.w.) and the groups AFs-contaminated diet plus low or high dose of Q. At the end of experiment, blood and liver samples were collected for biochemical, histological, histochemical and genetic analyses. The results indicated that animal fed AFs-contaminated diet showed significant increase in serum biochemical parameters, oxidative stress markers and DNA fragmentation accompanied with significant decrease in total proteins, GPX, SOD, DNA and RNA content and fatty acid synthase (Fas) and TNFα gene expression in the liver tissue. Q at the two tested doses succeeded to normalize the biochemical parameters, improved the content of nucleic acids in hepatic tissues, the gene expression, the histopathological and histochemical picture of the liver. It could be concluded that Q has a potential antioxidant activity, a protective action and regulated the alteration of genes expression induced by AFs.

Applications of polymeric nanoparticles (NP) in medical fields are rapidly expanding. However, the influence of polymeric NP on cell growth and functions is widely underestimated. Therefore, we have studied cell and polymeric NP interactions by addressing two cell types with two endpoints (viability and gene expressions). Rat NR8383 and human THP-1 monocytic cell lines were exposed to 6 to 200 μg/mL of Eudragit(®) RL NP for 24 h, and cellular viability was estimated using MTT, WST-1, and trypan blue tests. A decrease of viability was observed with NR8383 cells (down to 70% for 200 μg/mL), and on the contrary, an increase with THP-1 cells (up to 140% for 200 μg/mL). Differential expression of genes involved in oxidative damage (NCF1), inflammation (NFKB, TNFA, IL6, IL1B), autophagy (ATG16L), and apoptotic balance (PDCD4, BCL2, CASP8) was analyzed. ATG16L, BCL2, and TNFA were up-regulated in NR8383 cells, which are consistent with an induction of autophagy and inflammation. On the other hand, NCF1, NFKB, and IL1B were down-regulated in THP-1 cells, which may contribute to explain the increase of cellular viability. Our results show that (1) the toxic potency of NP is dependent on the cellular model used and (2) mechanistic toxicology should be the corner stone for the evaluation of NP hazard.

The aims of the current work were to evaluate the hepatoprotective effect of calendula flowers and/or thyme leave extracts on aflatoxins (AFs)-induced oxidative stress, genotoxicity and alteration of p53 bax and bcl2 gene expressions. Eighty male Sprague-Dawley rats were divided into eight equal groups including: the control group, the group fed AFs-contaminated diet (2.5 mg/kg diet) for 5 weeks, the groups treated orally with thyme and/or calendula extract (0.5 g/kg b.w) for 6 weeks and the groups pretreated orally with thyme and/or calendula extract 1 week before and during AFs treatment for further 5 weeks. Blood, liver and bone marrow samples were collected for biochemical analysis, gene expression, DNA fragmentation and micronucleus assay. The results showed that AFs induced significant alterations in oxidative stress markers, increased serum AFP and inflammatory cytokine, percentage of DNA fragmentation, the expression of pro-apoptotic gene p53 and bax accompanied with a decrease in the expression of bcl2. Animals treated with the extracts 1 week before AFs treatment showed a significant decrease in oxidative damage markers, micronucleated cells, DNA fragmentation and modulation of the expression of pro-apoptotic genes. These results suggested that both calendula and thyme extracts had anti-genotoxic effects due to their higher content of total phenolic compounds.

The aim of the current study was to evaluate the cardioprotective ability of water (WE) and ethanolic (EE) papaya fruits extracts against cardiotoxicity induced by aflatoxin B1 (AFB1) in rats. Forty two female Sprague-Dawley rats were divided into six treatment groups and treated orally for 2 weeks as follow: control group, the group treated with WE (250 mg/kg b.w), the group treated with EE (250 mg/kg b.w), the group treated orally with AFB1 (17 μg/kg b.w) and the groups treated orally with AFB1 plus WE or EE. The results indicated that treatment with AFB1 resulted in oxidative stress in the heart manifested by the marked increase in cardiac malondialdehyde and calcium levels accompanied with a significant decrease in cardiac total antioxidant capacity. Serum nitric oxide and sodium levels, lactate dehydrogenase and creatine kinase isoenzyme activities were significantly increased, whereas, cardiac Na(+)/K(+)-ATPase activity and serum potassium were insignificantly affected. Supplementation with WE or EE effectively ameliorated most of the changes induced by AFB1. It could be concluded that both extracts attenuated the oxidative stress induced in heart tissue by AFB1 and WE was more pronounced due to the higher total phenolic contents than in the EE.

The aim of this study was to prepare Eudragit Retard L (Eudragit RL) nanoparticles (ENPs) and to determine their properties, their uptake by the human THP-1 cell line in vitro and their effect on the hematological parameters and erythrocyte damage in rats. ENPs showed an average size of 329.0 ± 18.5 nm, a positive zeta potential value of +57.5 ± 5.47 mV and nearly spherical shape with a smooth surface. THP-1 cell lines could phagocyte ENPs after 2 h of incubation. In the in vivo study, male Sprague-Dawley rats were exposed orally or intraperitoneally (IP) with a single dose of ENP (50 mg/kg body weight). Blood samples were collected after 4 h, 48 h, one week and three weeks for hematological and erythrocytes analysis. ENPs induced significant hematological disturbances in platelets, red blood cell (RBC) total and differential counts of white blood cells (WBCs) after 4 h, 48 h and one week. ENP increased met-Hb and Co-Hb derivatives and decreased met-Hb reductase activity. These parameters were comparable to the control after three weeks when administrated orally. It could be concluded that the route of administration has a major effect on the induction of hematological disturbances and should be considered when ENPs are applied for drug delivery systems.

Liver diseases are amongst the most serious health problems in the world today and hepatocellular carcinoma is one of the world's deadliest cancers. The aim of the current study was to evaluate the protective effect of sider honey and/or Korean ginseng extract (KGE) against carbon tetrachloride (CCl(4))-induced hepato-nephrotoxicity in rat. Eighty male Sprague-Dawley (SD) rats were allocated into different groups and over a 4-week period, they orally received honey and/or KGE or were treated either with CCl(4) alone (100 mg/kg b.w) or with CCl(4) after a pretreatment period with honey, KGE or a combination of both. Clinical, clinico-pathological and histopathological evaluations were done and CCl(4)-treated groups were compared with rats receiving no treatment and with rats given honey, KGE or a combination of these substances. The results indicated that oral administration of CCl(4) induced severe hepatic and kidney injury associated with oxidative stress. The combined treatment with CCl(4) plus honey and/or KGE resulted in a significant improvement in all evaluated parameters. This improvement was prominent in the group receiving CCl(4) after combined pretreatment with honey and KGE. Animals receiving honey and/or KGE (without CCl(4)-treatment) were comparable to the control untreated group. It could be concluded that honey and KGE protect SD rats against the severe CCl(4)-induced hepatic and renal toxic effects. Our results suggest that the protective activity of honey and KGE may have been related to their antioxidant properties., (Copyright © 2011 Elsevier GmbH. All rights reserved.)

The aim of the present study was to investigate the cardiac biomarker changes in experimental bilateral ovariectomized (OVX) rats in addition to evaluating the role of soybean oil-supplemented diet to attenuate these alterations. Female rats were divided into four groups and treated for 2 months as follows: groups 1 and 2 fed with standard diet with or without 15% soybean oil. Groups 3 and 4 were bilateral OVX and received the standard diet with or without 15% soybean oil. The results revealed that rats subjected to ovariectomy exhibited an inhibition in estrogen and high-density lipoprotein cholesterol levels and marked increase of lipid profile, low-density lipoprotein cholesterol, and VLDL-C accompanied with a marked elevation in atherogenic index, cardiac enzyme activity, tumor necrosis factor-α, and C-reactive protein. Signs of cardiovascular injury which included an increase in cardiac thiobarbituric acid-reactive substances were concomitantly noticed with a reduction in the reduced glutathione, total antioxidant capacity, and superoxide dismutase. However, supplementation of soybean oil resulted in the restoration of the changed lipid profile and improved cardiac biomarkers near to normal values as well as improved inflammatory and antioxidant status. It was concluded that consumption of soybean oil may have a role in retarding atherosclerosis and risk of cardiovascular disorders associated with estrogen deficiency in ovariectomy status.

Aflatoxins (AF) are among the most potent naturally occurring carcinogens and aflatoxin-B1 (AFB(1)) is classified as a group-1 carcinogen. Since the ingestion of aflatoxins-contaminated food is associated with several liver diseases, the aim of the present study was to evaluate whether AF-induced damage in rats can be counteracted by feeding with whey-protein concentrates (WPC) and Korean ginseng extract (KGE). Eighty male Sprague-Dawley rats were divided into eight equal groups and treated daily for 30 days as follows: a control group (fed an AF-free diet), a group fed ad libitum an AF-contaminated diet (2.5mg/kg diet), a group treated orally with WPC (0.5ml/rat/day), a group treated orally with KGE (20mg/kg body weight), a group treated orally with WPC+KGE, and three groups that were fed the AF-contaminated diet and were treated orally with WPC, KGE or WPC+KGE, respectively. Throughout the experimental period, animals received WPC or KGE during the consumption of their respective diet. Bone-marrow micronucleus formation, DNA fragmentation, fatty-acid synthesis (FAS) and phospholipid-hydroperoxide-glutathione-peroxidase (PHGPx) mRNA expression, and oxidative stress were assayed in liver and testis. The results indicated that ingestion of aflatoxin resulted in a significant increase in micronucleated normochromatic erythrocytes (Mn-NCE) in bone marrow, DNA fragmentation, FAS mRNA expression and lipid peroxidation in both organs, and a significant decrease in micronucleated polychromatic erythrocytes/micronucleated normochromatic erythrocytes (PCE/NCE) ratio in bone marrow, PHGPx gene expression and GSH in liver and testis. Treatments with WPC and/or KGE had a significant effect on Mn-NCE or the PCE/NCE ratio in bone marrow. However, KGE or KGE+WPC increased PHGPx gene expression and GSH in testis accompanied with a significant decrease in lipid peroxidation in liver and testis and FAS-mRNA expression in liver. WPC, KGE or WPC+KGE treatments combined with exposure to an AF-contaminated diet restored all the test parameters towards control values, although they did not fully reverse the effects of the aflatoxins. It is suggested that the genotoxicity of aflatoxins can be in part prevented by dietary supplementation with WPC, KGE or their combination., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Radish (Raphanus sativus) has been extensively studied for its preventive effects against different degenerative diseases. Zearalenone (ZEN) is a mycotoxin produced by Fusarium spp and is frequently implicated in immunological disorders and occasionally in hyperoestrogenic syndromes contributing to the increased risk of cancer and other diseases. The aims of this study were, firstly, to quantitatively evaluate the Tunisian radish extract (TRE) for its total flavonoids, isothiocyanates and antioxidant activity and, secondly, to investigate the protective role of TRE against immune system disorders in Balb/c mice treated with ZEN for two weeks. The results indicated that mice treated with ZEN (40 mg kg(-1)) alone showed a significant decrease in lymphocytes of the total white blood cells, immunoglobulin profile (IgG and IgM), B cells, T-cell sub-types (CD3+, CD4+ and CD8+) and natural killer and pro-inflammatory cytokines. Mice treated with TRE (5, 10 or 15 mg kg(-1)) for 7 days before, during or after ZEN treatment, however, showed a significant improvement in lymphocyte, immunoglobulin profile, T-cell sub-types, B cells and pro-inflammatory cytokines. Moreover, treatment with the highest dose of TRE (15 mgkg(-1)) enhanced the release of tumour necrosis factor-alpha and interleukin-1beta but the other parameters were comparable with those of the control. It could be concluded that TRE was effective in protecting against ZEN-induced immunological disorders. These results supported our hypothesis that TRE contains several compounds that are able to prevent or inhibit ZEN toxicity.

Aflatoxins (AF), a group of closely related, extremely toxic mycotoxins, produced by Aspergillus flavus and A. parasiticus can occur as natural contaminants of foods and feeds. Aflatoxins have been shown to be hepatotoxic, carcinogenic, mutagenic, and teratogenic to different animal species. Zizyphus spina-christi L. extract was investigated for its antifungal and antimicrobial activities. The aim of the present work was to evaluate the antioxidant activity of the methanol extract of Z. spina-christi L. leaves against the oxidative stress of aflatoxin in rats. Fourty male Sprague-Dawley male rats were divided into four groups including the control group, the group fed aflatoxin-contaminated diet (3 mg/kg diet) and the groups treated with Zizyphus extract (5 mg/kg b.w) alone or in combination with AF for 15 days. Biochemical analysis revealed that treatment with AF resulted in a significant increase in ALT, AST, cholesterol, triglycerides, uric acid, TNFa, LPO, NO and CEA, whereas it decrease significantly GPX and SOD. The histopathological examination of the liver, kidney and testis showed sever histological changes typical to those reported for aflatoxicosis. Animals treated with Zizyphus extract alone or plus AF showed a significant improvement in all biochemical parameters and histological picture of liver, kidney and testis. It could be concluded that Zizyphus extract have a power protective role against aflatoxicosis.