Chitosan Nanoparticles Loaded with Capparis cartilaginea Decne Extract: Insights into Characterization and Antigenotoxicity In Vivo.

Plant-based foods may enhance the prevention of cancer. The present investigation aimed to assess the antigenotoxic effects of chitosan nanoparticles (CNPs) when loaded with the ethanol extract of C. cartilaginea (CNPs/Cc). Synthesis of CNPs and CNPs/Cc and their characterization were carried out using TEM, EDS, DSC, and Zeta potential. For in vivo experiments, animal groups were treated in the following groups: negative control, ethyl methanesulfonate (EMS) (240 mg/kg), CNPs (350 mg/kg), high and low doses of CNPs/Cc, CNPs plus EMS, high dose of CNPs/Cc plus EMS, and low dose of CNPs/Cc plus EMS. Bone marrow chromosomal aberrations and sperm shape abnormalities were examined. TEM results showed that CNPs and CNPs/Cc are spherical particles. CNPs' physical stability was observed to be lower than that of CNPs/Cc due to the presence of more positive charges on CNPs/Cc. EMS significantly enhanced chromosomal abnormalities and sperm shape abnormalities. CNPs showed powerful antigenotoxic properties. For the first time, it could be concluded that loading chitosan nanoparticles with C. cartilaginea extract significantly promotes its protective properties.

FTIR microscopy evaluation of the immunogenicity of eco-friendly γFe2O3@Ag@Cs nanocomposite as a platform for the discovery and screening of vaccine adjuvants.

Core-shell nanoparticles have been extensively researched, particularly as multimodal for medical applications. Scientists are interested in combining the optical properties of nano-plasmonic nanoparticles with the magnetic properties of super-paramagnetic nanoparticles. This combination is very important because it reduces metal toxicity and improves nanoparticle targeting. Tuning the shape and size of the nanoparticles significantly reflects their properties and applications. In previous study, we assessed the SPION@Ag@chitosan core-shell nanocomposite (γFe2O3@Ag@Cs NCs) toxicity both in vitro and preclinically in vivo, using traditional toxicological assessment and biochemical parameters. The results showed that up to100 ug/kg is a safe NP dose as evaluated by pathological and biochemical parameters. The aim of the present study was to gain insight into the effect of γFe2O3@Ag@Cs NC at sub-cytotoxic concentrations (100ug/ml) on the biochemical profile of immune organs (inguinal, axillary, spleen and thymus) by combining the investigation of cytokine secretion to ex vivo FTIR spectroscopy. The four immune organs were treated with 100 ug/kg NC and the time dependence of the effects produced by the treatment was analyzed. The Data shows that the used core-shell NC with the indicate dose have a stimulatory effect on the immune system, as evidenced by an increase in antibody secretion (IgG and IgM), lipid, nucleic acid, and protein synthesis after uptake time which depends on the specific immune organ.

Antimicrobial, Antigenotoxicity, and Characterization of Calotropis procera and Its Rhizosphere-Inhabiting Actinobacteria: In Vitro and In Vivo Studies.

Calotropis procera (C. procera) is a wild shrub that is a medicinal plant found in abundance throughout Saudi Arabia. In this study, we investigated the phytochemical composition and antigenotoxic properties of the ethanolic extract of C. procera, in addition to the antimicrobial activity of the plant and its rhizospheric actinobacteria effects against pathogenic microorganisms. Soil-extract medium supplemented with glycerol as a carbon source and starch-casein agar medium was used for isolation of actinobacteria from rhizosphere. From the plant, a total of 31 compounds were identified using gas chromatography/mass spectrometry (GC-MS). The main components were α-amyrin (39.36%), lupeol acetate (17.94%), phytol (13.32%), hexadecanoic acid (5.55%), stigmasterol (3.16%), linolenic acid (3.04%), and gombasterol A (2.14%). C. procera plant extract's antimicrobial activity was investigated using an agar well-diffusion assay and minimum inhibitory concentration (MIC) against six pathogenic microbial strains. The plant extract of C. procera was considered significantly active against Staphylococcus aureus, Klebsiella pneumonia, and Escherichia coli, with inhibition zones of 18.66 mm, 21.26 mm, and 21.93 mm, respectively. The plant extract was considered to be a moderate inhibitor against Bacillus subtilis, with MIC ranging from 0.60-1.50 mg/mL. On the other hand, the isolated actinobacteria were considered to be a moderate inhibitor against S. aureus (MIC of 86 µg/mL), and a potent inhibitor, strain CALT_2, against Candida albicans (MIC of 35 µg/mL). The 16S rRNA gene sequence analysis showed that the potential strains belonged to the genus Streptomyces. The effect of C. procera extract against cyclophosphamide (CP)-induced genotoxicity was examined by evaluating chromosome abnormalities in mouse somatic cells and DNA fragmentation assays. The current study revealed that oral pretreatment of C. procera (50, 100, and 200 mg/kg b.w.) for 1, 7, and 14 days to cyclophosphamide-treated animals significantly reduced chromosomal abnormalities as well as DNA fragmentation in a dose-dependent manner. Moreover, C. procera extract had antimicrobial and antigenotoxic effects against CP-induced genotoxicity.

Assessment of the Antigenotoxic Effects of Alginate and ZnO/Alginate-Nanocomposites Extracted from Brown Alga Fucus vesiculosus in Mice.

Mitomycin C (MMC) is an alkylating chemotherapy drug that could induce DNA damage and genetic alteration. It has been used as a model mutagen for in vivo and in vitro studies. The current study aimed to evaluate the protective role of Zinc oxide alginate-nanocomposites (ZnO-Alg/NCMs) against MMC-induced genotoxicity in mice. Animals were treated as follows: the control group, the groups treated with Algin (400 mg/kg b.w), the groups treated with ZnO-Alg/NCMs (400 mg/kg b.w), the group treated with MMC, and the groups treated with MMC plus Algin or ZnO-Alg/NCMs. Pre-treatment with Algin and ZnO-Alg/NCMs was repeated for one or seven days. Zinc oxide alginate-nanocomposites (ZnO-Alg/NCMs) were synthesized with the aim of incorporating the intrinsic properties of their constituents as an antigenotoxic substance. In this study, alginate was extracted from the brown marine alga Fucus vesiculosus, Zinc oxide nanoparticles were synthesized by using water extract of the same alga, and loaded in alginate to synthesize ZnO-Alg/NCMs. ZnO-NPs and ZnO-Alg/NCMs were characterized by TEM, SEM, EDX, and Zeta potential. The obtained results confirmed that by TEM and SEM, ZnO-NPs are rod shaped which modified, when loaded in alginate matrix, into spherical shape. The physical stability of ZnO-Alg/NCMs was reported to be higher than ZnO-NPs due to the presence of more negative charges on ZnO-Alg/NCMs. The EDX analysis indicated that the amount of zinc was higher in ZnO-NPs than ZnO-Alg/NCMs. The in vivo results showed that treatment with MMC induced genotoxic disturbances. The combined treatment with Algin and ZnO-Alg/NCMs succeeded in inducing significant protection against MMC. It could be concluded that ZnO-Algin/NCMs is a promising candidate to protect against MMC-induced genotoxicity.

Matlodextrin-cinnamon essential oil nanoformulation as a potent protective against titanium nanoparticles-induced oxidative stress, genotoxicity, and reproductive disturbances in male mice.

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 (TiO2NP)-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, TiO2NP-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 TiO2NPs 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 TiO2NPs and ECO were 28.9 and 321 nm and -33.97 and -17.35 mV, respectively. TiO2NP 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 TiO2NPs 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 TiO2NPs.

Improved hepatoprotective activity of Beta vulgaris L. leaf extract loaded self-nanoemulsifying drug delivery system (SNEDDS): in vitro and in vivo evaluation.

OBJECTIVE: Beta vulgaris L. (beetroot) is a vegetable plant rich in phytochemical compounds such as phenolic acids, carotenoids and flavonoids. The objective of the current study is the development and optimization of self-nanoemulsifying drug delivery systems (SNEDDSs) to enhance the hepatoprotective activity of beet leaf (BL) extract. METHODS: Total flavonoids content was estimated in the BL extract and its solubility was evaluated in various vehicles to select proper component combinations. Pseudo-ternary phase diagrams were constructed employing olive, linseed, castor and sesame oils (oil phase), Tween® 20 (Tw20) and Tween® 80 (Tw80) (surfactants (SAs)) as well as dimethyl sulfoxide (DMSO) and propylene glycol (PG) (co-surfactants (Co-SAs)). Optimization of formulations from the phase diagrams took place through testing their thermodynamic stability, dispersibility and robustness to dilution. RESULTS: Four optimized BL-SNEDDS formulations, comprising linseed oil or olive oil, Tw80 and DMSO at two SA/Co-SA ratios (2:1 or 3:1) were chosen. They exhibited high cloud point and percentage transmittance values with spherical morphology of mean droplet sizes ranging from 14.67 to 16.06 nm and monodisperse distribution with negatively charged zeta potential < -9.51 mV. The in vitro release profiles of the optimized formulations in pH 1.2 and 6.8 were nearly similar, with a non-Fickian release mechanism. In vivo evaluation of BL-SNEDDSs hepatoprotective activity in a thioacetamide-induced hepatotoxicity rat model depicted promoted liver functions, inflammatory markers and histopathological findings, most prominently in the group treated by F7. CONCLUSION: The results indicate that SNEDDS, as a nanocarrier system, has potential to improve the hepatoprotective activity of the BL extract.

Virucidal Action Against Avian Influenza H5N1 Virus and Immunomodulatory Effects of Nanoformulations Consisting of Mesoporous Silica Nanoparticles Loaded with Natural Prodrugs.

BACKGROUND: Combating infectious diseases caused by influenza virus is a major challenge due to its resistance to available drugs and vaccines, side effects, and cost of treatment. Nanomedicines are being developed to allow targeted delivery of drugs to attack specific cells or viruses. MATERIALS AND METHODS: In this study, mesoporous silica nanoparticles (MSNs) functionalized with amino groups and loaded with natural prodrugs of shikimic acid (SH), quercetin (QR) or both were explored as a novel antiviral nanoformulations targeting the highly pathogenic avian influenza H5N1 virus. Also, the immunomodulatory effects were investigated in vitro tests and anti-inflammatory activity was determined in vivo using the acute carrageenan-induced paw edema rat model. RESULTS: Prodrugs alone or the MSNs displayed weaker antiviral effects as evidenced by virus titers and plaque formation compared to nanoformulations. The MSNs-NH2-SH and MSNs-NH2-SH-QR2 nanoformulations displayed a strong virucidal by inactivating the H5N1 virus. They induced also strong immunomodulatory effects: they inhibited cytokines (TNF-α, IL-1ß) and nitric oxide production by approximately 50% for MSNs-NH2-SH-QR2 (containing both SH and QR). Remarkable anti-inflammatory effects were observed during in vivo tests in an acute carrageenan-induced rat model. CONCLUSION: Our preliminary findings show the potential of nanotechnology for the application of natural prodrug substances to produce a novel safe, effective, and affordable antiviral drug.

Design, synthesis and anticonvulsant activity of new imidazolidindione and imidazole derivatives.

New imidazolidindiones and tetra-substituted imidazole derivatives were designed, synthesized, and evaluated for the anticonvulsant activity through pentylenetetrazole (PTZ)-induced seizures and maximal electroshock (MES) tests using valproate sodium and phenytoin sodium as reference drugs, respectively. Most of the target compounds showed excellent activity against pentylenetetrazole (PTZ)-induced seizures with fair to no-activity against MES. Compounds 3d, 4e, 11b, and 11e showed higher activity (120%) than that of valproate sodium in PTZ model. Almost all compounds showed no neurotoxicity, as indicated by the rotarod test. Estimation of physicochemical properties and pharmacokinetic profiles of the target compounds were studied. The chemical structures of the target compounds were characterized by different spectrometric methods and elemental analysis.

Bioactive compounds from Aspergillus niger extract enhance the antioxidant activity and prevent the genotoxicity in aflatoxin B1-treated rats.

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 B1 (AFB1)-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, AFB1-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 AFB1 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 AFB1 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.

Secondary metabolites from Bacillus sp. MERNA97 extract attenuates the oxidative stress, genotoxicity and cytotoxicity of aflatoxin B1 in rats.

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 AFB1. Sixty male Sprague-Dawley rats were divided into 6 groups and treated for 6 weeks and included the control group, AFB1-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 AFB1 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 AFB1 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.

Synthesis, pharmacological profile and 2D-QSAR studies of curcumin-amino acid conjugates as potential drug candidates.

A series of curcumin bis-conjugates 3a-q, 5a-k and 6a-k were synthesized in good yields utilizing an optimized reaction condition. We explored the effect of different amino acids and protecting groups on biological activities of curcumin. The conjugates were screened for anti-inflammatory, analgesic and antimicrobial properties. Some of the conjugates showed promising biological observations with a potency comparable with the standard references. The variations in biological properties concerning different amino acids and protecting groups are interesting observations. Effects of the synthesized conjugates on splenocytes and the production of nitric oxide by lipopolysaccharide-stimulated peritoneal macrophages are correlated with the observed anti-inflammatory properties. We have also established the safety profile of the most active conjugates. Robust 2D-QSAR studies supported and validated biological data.

CD40L membrane retention enhances the immunostimulatory effects of CD40 ligation.

In carcinomas, the nature of CD40 ligand shapes the outcome of CD40 ligation. To date, the consequences of membrane-bound CD40L (mCD40L) on its immune-stimulatory function are unknown. Here, we examined the impact of mCD40L versus soluble CD40L (sCD40L) on T24 bladder carcinoma gene expression profiling. Of 410 differentially expressed genes, 286 were upregulated and 124 downregulated by mCD40L versus sCD40L. Gene ontology enrichment analysis revealed immune-stimulatory function as the most significant enriched biological process affected by upregulated transcripts, while those downregulated were critical for cell growth and division. Furthermore, immature dendritic cells (iDC) responded to mCD40L with enhanced maturation and activation over sCD40L evidenced by higher expression levels of CD83, CD86, HLA-DR and CD54, increased secretion of IL12 and IL10 and higher tumour-antigen (TA) uptake capacity. Furthermore, autologus CD3+ T cells responded to TA-loaded mCD40L-activated DC with increased proliferation and cytotoxic response (CD107a and IFN-γ-producing CD3+ CD8+ T cells) to the tumour-loaded autologous PBMCs compared to sCD40L. Thus, these data indicate that mCD40L enhances the immunostimulatory capacity over sCD40L. Furthermore, the ability of mCD40L to also directly induce cell death in CD40-expressing carcinomas, subsequently releasing tumour-specific antigens into the tumour microenvironment highlights the potential for mCD40L as a multi-faceted anti-cancer immunotherapeutic.

Chemometric evaluation of alfalfa sprouting impact on its metabolic profile using HPTLC fingerprint-efficacy relationship analysis modelled with partial least squares regression.

Sprouting is a commonly applied food processing practice specially in Western countries. Tracking the impact of sprouting of Medicago sativa L. (alfalfa) seeds on their phytochemical composition and curative efficacy was implemented in the current study. Sprouting of alfalfa seeds under controlled conditions for eleven days was performed in a biochemical incubator and three samples were randomly taken each day. A total of thirty-six samples (three ungerminated seeds and thirty-three sprouts samples) were collected, extracted and their cytotoxic, antioxidant and antimicrobial activities against five pathogenic microbial strains were measured. Samples were subjected to High performance thin layer chromatography (HPTLC) as a pattern-oriented strategy for metabolite fingerprinting to discover the fluctuations occurring during the sprouting process accompanied by multivariate chemometric analysis. Unsupervised pattern recognition was carried out using Principal Component Analysis (PCA) after extracting the chromatographic fingerprints from HPTLC chromatograms using ImageJ® software. PCA- loading plots demonstrated that luteolin-7-O-glucoside, ferulic acid and P-coumaric acid were the metabolically significant markers. Thus, simultaneous quantification of these crucial three markers in different aged alfalfa seeds/ sprouts extracts was performed using a newly developed and validated HPTLC-image analysis method. The results of the biological activities together with the quantitative data were further subjected to a Partial Least Squares Regression (PLSR) model for implementing HPTLC fingerprint-efficacy relationship analysis. The results obtained from metabolic pool profiling revealed that sprouting can cause remarkable changes in the phytochemical, nutritional and efficacy characteristics of alfalfa seeds.

Design, synthesis and anticancer evaluation of novel 1,3-benzodioxoles and 1,4-benzodioxines.

A new set of 1,3-benzodioxoles and 1,4-benzodioxines was designed and synthesized starting from gallic acid as anticancer agents. The antiproliferative effect of the target compounds was evaluated against a panel of cancer cell lines (HepG2, PC-3, MCF-7 and A549) using MTT assay. The 1,4-benzodioxine derivative 11a manifested broad spectrum effect towards the four tested cancer cell lines (IC50 < 10 µM) with lower toxic effect on normal human cell line BJ1. Cell cycle progression of MCF-7 after treatment with compound 11a was studied where it induced cells accumulation at G2/M phase as well as increasing in the percentage of cells at pre-G1. Compound 11a is found to be a tubulin polymerization inhibitor with IC50 = 6.37 µM. Also, flow cytometeric analysis revealed that compound 11a could induce both early and late stage apoptosis in MCF-7 cell line. Moreover, the ability of this compound to stimulate apoptosis in the latter cell line was further confirmed by: increment of Bax/Bcl-2 ratio, increase the expression of tumor suppressor gene p53, boosting the levels of initiator and executioner caspases as well as raise in the amount of cytochrome C. In addition molecular docking study was accomplished on the colchicine binding site of tubulin (pdb: 1SA0) to illustrate the interactions of the most potent compound 11a to the receptor.

Anticancer activity of newly synthesized 1,1-disubstituted cyclohexane-1-carboxamides: in vitro caspases mediated apoptosis activators in human cancer cell lines and their molecular modeling.

Novel 1,1-disubstituted cyclohexane-1-carboxamides 6a-h, 7a-e, and 8a-b were designed and synthesized as apoptotic inducers. Cytotoxicity test revealed that some compounds have strong to moderate effect, while others displayed weak action against different cancer cell lines including, MCF-7, HepG2, A549, and HTC-116. A549 carcinoma cell line exhibited higher sensitivity toward all synthesized candidates especially compounds 6a and 8a which offered the lowest IC50 values 3.03 and 5.21 µM, respectively, relative to the positive control doxorubicin with IC50 value of 3.01 µM. Compared to doxorubicin treatment, compounds 6a and 8a induced caspases-3, -8, and -9 activities and G2/M growth arrest in A549 carcinoma cell line. The expression levels of p53 (tumor suppressor protein that in humans is encoded by the TP53 gene), Bax (apoptosis regulator protein in humans that is encoded by bax gene), and the Bax/Bcl-2 ratio were all higher than those in doxorubicin-treated cells (Bcl-2, B-cell lymphoma 2, encoded in humans by the Bcl-2 gene). Additionally, compounds 6a and 8a appeared to exhibit higher selectivity against MCF-10 human breast normal cell line. The synthesized congeners could be considered as potent apoptotic inducers interfering with extrinsic and intrinsic apoptotic pathways. Moreover, compound 6a was able to form complex with zinc ions as indicated by UV spectrophotometry which revealed its ability for being caspase activator. Molecular docking studies expected the interactions and binding modes of the synthesized inhibitors in the caspase-3 active site.

Synthesis & molecular modeling studies of bronchodilatory active indole-pyridine conjugates.

AIM: Synthesis of novel bronchodilatory active indole-pyridine conjugates. Results/methodology: Indole-pyridine conjugates (6a-n, 8a-i and 10a-c) were synthesized in a facile pathway through reaction of 2-[(1-alkyl-1H-indol-3-yl)methylene]malononitriles 4a,b with the corresponding ketone-containing compounds (5a-f, 7a-c and 9a,b) in the presence of sodium alkoxide. Single (6l, 8 g) and powder (6k, 8d) x-ray studies supported the structures. RESULTS: Histamine precontracted isolated tracheal rings of guinea pig exhibited the potent bronchodilation properties of 6c (about double-fold potency relative to the standard reference, theophylline). Some of the synthesized conjugates (8d, 6c, 6f and 6e) revealed promising reduction of IL-8 production during lipopolysaccharide-induced airway inflammatory bioassay. Computational studies (3D pharmacophore, 2D-QSAR 'quantitative structure-activity relationship') showed high approximations to the bronchodilation properties and explained the parameters controlling biological observations.

Purification and characterization of a new thermophilic collagenase from Nocardiopsis dassonvillei NRC2aza and its application in wound healing.

A thermostable metallo-collagenase enzyme (150 kDa), recently identified in a newly isolated actinomycestes strain (Nocardiopsis dassonvillei NRC2aza), has been purified from natural source, characterized to have application in wound healing. A simple 3 step purification procedure gave an increase of purity by 6.23 fold with a specific activity of 387.2 U mg-1. The enzyme activity showed stability across a range of pH (7.0-8.5) and temperature (40-55 °C) with optima at pH 8.0 and 60 °C, respectively. Activators include Mg+2, Ca+2, Zn+2, Na+, K+ and Ba+2, while Mn+2, Co+2, Ni+2and Ag+ ions gave partial inhibition. Full inhibition was given by other tested ions and metalloproteinase inhibitors. Broad substrate specificity was demonstrated including activity against a native collagen. The Km and Vmax of the enzyme using azocollagen were 5.5 mg/ml and 1280 U, respectively. The purified collagenase enhanced wound closure in vitro and in vivo and the repair process was dose dependent. Topical application of the purified collagenase (either of 25 or 50 U) to cutaneous wounds significantly accelerated the rate of wound healing and the formation of granulation tissue. Hence, the purified collagenase has a great potential as a therapeutic agent in wound care and collagen related diseases.

Protective capabilities of silymarin and inulin nanoparticles against hepatic oxidative stress, genotoxicity and cytotoxicity of Deoxynivalenol in rats.

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.

Evaluation of the bioactive extract of actinomyces isolated from the Egyptian environment against aflatoxin B1-induce cytotoxicity, genotoxicity and oxidative stress in the liver of rats.

This study aimed to determine the bioactive compounds of actinomyces (ACT) isolated from the Egyptian environment (D-EGY) and to evaluate their protective activity against AFB1 in female Sprague-Dawley rats. Six groups of animals were treated orally for 3 weeks included: C, the control group, T1, AFB1-treated group (80 µg/kg b.w), T2 and T3, the groups received ACT extract at low (25 mg/kg b.w) or high (50 mg/kg b.w) doses, T4 and T5, the groups received AFB1 plus the low or high dose of ACT extract. Blood, bone marrow and tissue samples were collected for different analyses and histological examination. The results revealed the identification of 40 components, representing 99.98%. Treatment with AFB1 disturbs liver function parameters, oxidative stress markers, antioxidant gene expressions, DNA fragmentation and induced severe histological changes. ACT extract at the low or high doses did not induce significant changes in all the tested parameters or histological picture of the liver. Moreover, ACT extract succeeded to induce a significant protection against the toxicity of AFB1. It could be concluded that the bioactive compounds in ACT are promise candidate for the development of food additive or drugs for the protection and treatment of liver disorders in the endemic area.