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Aim: Leukemia is a malignant clonal illness stem from the mutations of hematopoietic cells. Acute lymphoblastic leukemia is one of the utmost prevalent kinds of leukemia, is brought on by atypical lymphoid progenitor cell division in the bone marrow. Materials & methods: A comparative study between, titanium Nanoparticle-loaded doxorubicin or cisplatin and lactoferrin-loaded doxorubicin or cisplatin, on 7,12-dimethylbenz[a]-anthracene (DMBA)-induced leukemia was investigated and confirming the hypothesis that messenger RNA of Hprt/K-RAS/c-Myc/SAT-2/P53/JAK-2 is a forthcoming signaling pathways in leukemia. Results: A significant alteration in Hprt, K-RAS, C-Myc, P53, JAK-2 and SAT-2 genes was observed post DMBA intoxication the aforementioned Nanodrugs modulated these signaling pathways. Conclusion: The carrier-loaded drugs triggered cytotoxicity of cancer cells via enhancing drug efficacy and bio-availability.
Leukemia is the abnormal growth of white blood cells that is responsible for fighting infection. Cisplatin and doxorubicin are commonly used anticancer drugs that can combat leukemic cells however they faced some problems of poor solubility and toxicity to normal cells. Thus we designed nanodrugs as Ti-NPs-cisplatin or DOX and lactoferrin-cisplatin or DOX and compared them with DOX and cisplatin and studied their impact on DMBA-induced leukemia in rat models. Monitoring apoptotic and cell survival genes was performed. Treatment with the nanodrugs could be promising in targeting cancer cells and improving drug bio-availability thus inducing cancer cell death.
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Aim: To clarify the alternation of gene expression responsible for resistance of Adriamycin (ADR) in rats, in addition to investigation of a novel promising drug-delivery system using titanium dioxide nanoparticles loaded with ADR (TiO2-ADR). Method: Breast cancer was induced in female Sprague-Dawley rats, followed by treatment with ADR (5 mg/kg) or TiO2-ADR (2 mg/kg) for 1 month. Results: Significant improvements in both zinc and calcium levels were observed with TiO2-ADR treatment. Gene expression of ATP-binding cassette transporter membrane proteins (ABCA1 & ABCG1), P53 and Jak-2 showed a significant reduction and overexpression of the C-myc in breast cancer-induced rats. TiO2-ADR demonstrated a notable ability to upregulate these genes. Conclusion: TiO2-ADR could be a promising drug-delivery system for breast cancer therapy.
The current study aimed to investigate a novel and promising drug-delivery system to overcome the resistance problem by loading Adriamycin (ADR) into titanium dioxide nanoparticles (TiO2). The study also aimed to clarify the changes in gene expression responsible for the development of ADR resistance, in a rat model. First, animals were divided into four groups of ten each. Breast cancer was induced in female Sprague-Dawley rats by administering two doses of DMBA (50 and 25 mg/kg), followed by treatment with ADR at a dose of 5 mg/kg for 1 month, or TiO2-ADR at a dose of 2 mg/kg for 1 month. Biochemical and molecular analyses were conducted. Zinc and calcium levels were found to significantly decrease after cancer induction. Treatment with ADR alone or in combination with TiO2 showed a significant improvement in both mineral levels, with the TiO2-ADR group showing superior results. Gene expression of ATP-binding cassette transporter membrane proteins (ABCA1 & ABCG1), P53 and Jak-2 showed a significant decrease after DMBA-induced breast cancer. However, both the ADR- and TiO2-ADR-treated groups showed a notable increase in gene expression, with the TiO2-ADR group showing the highest increase. On the other hand, there was a significant overexpression of the C-myc gene after DMBA-induced breast cancer. However, both ADR and TiO2-ADR treatments resulted in a notable decrease in C-myc gene expression. Based on the data, TiO2-ADR could be a promising drug-delivery system for breast cancer therapy.
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CRISPR/Cas9 is a recently discovered genomic editing technique that altered scientist's sight in studying genes function. Cas9 is controlled via guide (g) RNAs, which match the DNA targeted in cleavage to modify the respective gene. The development in prostate cancer (PC) modeling directed not only to novel resources for recognizing the signaling pathways overriding prostate cell carcinoma, but it has also created a vast reservoir for complementary tools to examine therapies counteracting this type of cancer. Various cultured somatic rat models for prostate cancer have been developed that nearly mimic human prostate cancer. Nano-medicine can passively target cancer cells via increasing bioavailability and conjugation via specific legend, contributing to reduced systemic side-effects and increased efficacy. This article highlights liposomal loaded Nano-medicine as a potential treatment for prostate cancer and clarifies the CRISPR/Cas9 variation accompanied with prostate cancer. PC is induced experimentally in western rat model via ethinyl estradiol for 4 weeks and SC. dose of 3, 2'- dimethyl-4-aminobiphenyl estradiol (DAE) (50mg/kg) followed by treatment via targeted liposomal-coated compounds such as liposomal dexamethasone (DXM), liposomal doxorubicin (DOX) and liposomal Turmeric (TUR) (3mg/kg IP) for four weeks in a comparative study to their non-targeted analogue dexamethasone, doxorubicin and Turmeric. 3, 2'- dimethyl-4-aminobiphenylestradiol elicit prostate cancer in western rats within 5 months. Simultaneous supplementations with these liposomal compounds influence on prostate cancer; tumor markers were investigated via prostate-specific antigen (PSA), Nitric oxide (NOX) and CRISPR/Cas9 gene editing. Several long non-coding RNAs were reported to be deregulated in prostate cell carcinoma, including MALAT1. On the other hand, gene expression of apoptotic biomarkers focal adhesion kinase (AKT-1), phosphatidylinistol kinase (PI3K) and glycogen synthase kinase-3 (GSK-3) was also investigated and further confirming these results via histopathological examination. Liposomal loaded dexamethasone; doxorubicin and Turmeric can be considered as promising therapeutic agents for prostate cancer via modulating CRISPR/Cas9 gene editing and long non coding gene MALAT1.
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Sistemas CRISPR-Cas , Liposomas , Neoplasias de la Próstata , ARN Largo no Codificante , Masculino , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/diagnóstico , Animales , Ratas , ARN Largo no Codificante/genética , Sistemas CRISPR-Cas/genética , Humanos , Edición Génica/métodosRESUMEN
Aim: Drug resistance is still a significant barrier to effective hepatocellular carcinoma therapy. Address the issue of doxorubicin resistance and inter-receptor crosstalk various doxorubicin formulations were investigated. Methods: Hepatocellular carcinoma was carried out using 3-methylechloroanthrene. Animals were then treated with doxorubicin, liposomal doxorubicin, titanium-loaded doxorubicin (TiO2-Dox), lactoferrin-doxorubicin and PEGylated doxorubicin. Biochemical and molecular analyses were assessed. Results: Results have declared a significant alternation of both sodium and potassium concentrations upon 3-methylechloroanthrene administration. Arginase-I and α-L-Fucodinase tumor biomarkers were significantly elevated. C-myc, Hprt-1 and EGFR gene expression were over-expressed. Treatment with the aforementioned treatment regimens significantly modulated all measured parameters. Conclusion: TiO2-Dox, doxorubicin-lactoferrin and PEGylated doxorubicin could be a promising regimen in hepatocellular carcinoma and overcoming the problem of drug resistance.
[Box: see text].
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Carcinoma Hepatocelular , Doxorrubicina , Polietilenglicoles , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Doxorrubicina/análogos & derivados , Animales , Polietilenglicoles/química , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Sistemas de Liberación de Medicamentos/métodos , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/efectos adversos , Titanio/toxicidad , Lactoferrina/administración & dosificación , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Masculino , Humanos , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genéticaRESUMEN
MALAT-1 is extremely elevated in human malignancies thus functions as a prognostic biomarker. Nevertheless, limited data has been discovered concerning MALAT's contribution in stomach cancer. MALAT-1 expression appeared considerably greater in gastric cancer (GC) rats with remote miR-122-IGF-1R impact. MALAT-1 depletion inhibited cell cycle development, cell division and invasion, thus boosting death of GC cells. Likewise, miR-122-IGF-1R expression was linked to MALAT-1 deregulations in GC. Biological markers discovery based on biochemical data alongside detailed genome study might enhance prognosis, diagnosis and therapeutic compliance. This article summed up the most recent developments and techniques in GC biomarkers and may have applications for early detection, precise estimation of treatment strategies, and future perspectives according to molecular classification and profiling. In rats, GC was induced by 20-MCA, followed by DOX, Liposomal DOX, and PEGylated-Dox treatment. In addition to histopathological examinations, GC tumor biomarkers such as CEA, CA12-5, KRAS, AKT, PTEN, TP53, JAK-2, lnc- MALAT-1 and miR-122-IGF-1R were tracked. These findings reveal that MALAT-1 may be oncogenic in GC. Prominent MALAT-1 levels may assist as an indicator of metastasis in GC, and that miR-122-IGF-1R expression is associated via reduced MALAT-1 signaling. Finally, PEG-DOX may be an excellent option for GC therapy.
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Autism spectrum disorder, or individual disability (ID), is a condition characterized by complications in social interaction, restricted repetitive behavior, and difficulties in social communication. Neuquinon (NQ) possess a powerful therapeutic potential in various neurodegenerative disease. Nevertheless, contributing to NQ's low water solubility and bioavailability, its medicinal use has been constrained. Liposomes were supposed to be prospective drug-delivering agents for NQ, crossing the blood-brain barrier (BBB), and reaching the target organs. The current investigation aims to track the signaling pathways that govern NQ and liposomal neuquinon (LNQ) action in autistic models generated by ethyl formic acid. The neurotransmitters gamma amino-butyric acid (GABA), acetylcholine (ACh), and acetylcholinesterase (AChE) in addition to, the gene expressions of brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), and methyl-CpG-binding protein 2 (MeCP2) and the DNA damage COMET analysis at different time intervals of the study, were assessed. EFA in a dose of 500 mg/kg BW was used to induce autism in rats, and then NQ and LNQ were administered in 10 mg/kg and 2 mg/kg BW, respectively. The results revealed that NQ and LNQ significantly down-regulated BDNF, GABA, and AChE; on the other hand, they up-regulated MeCP2, CREB gene expressions, and ACh action. NQ and LNQ displayed improvement in DNA damage in almost all brain regions after EFA alterations; even better results were noticed post-LNQ therapy. Therefore, it may be concluded that neuquinon and liposomal-loaded neuquinon have a therapeutic index versus EFA-induced autism in a rat model.
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Background: Cobalt chloride (CoCl2) is a ferromagnetic ubiquitous trace element extensively dispersed in the environment. Nevertheless, it may merit human hazard. Aim: Excess cobalt can harm vital organs this paves the way to elucidate the toxic impact of CoCl2 on the liver, kidney and heart. Method: CoCl2 was injected in a dose of (60 mg/kg, S.C.) proceeded via Carnosine (200 mg/kg) and/or Arginine (200 mg/kg) treatment 1 month, 24 and 1 h, prior to CoCl2-intoxication. Results: CoCl2 significantly alleviated hemoglobin concentration and BCl2; meanwhile, protein expression of transforming growth factor (TGF-ß), hypoxia-inducible factor (HIF-1α), Mothers against decapentaplegic (Smad-2), AKT protein expression and Bax/Bcl2 ratio was noticeably elevated. Conclusion: The combination of the aforementioned antioxidants exerted a synergistic anti-apoptotic impact in all target tissues.
Cobalt chloride (CoCl2) is commonly found in the environment and used in medicine. However, it can be harmful to our health, particularly when consumed in excessive amounts, leading to damage in important organs. Therefore, we investigated the toxic effects of CoCl2 on the liver, kidney, and heart. We also explored potential treatments using substances like Carnosine and Arginine. We discovered that Arginine and carnosine had a positive effect on certain factors related to the health of the organs. They helped regulate the levels of hemoglobin and BCl2, as well as the expression of proteins such as transforming growth factor (TGF-ß), hypoxia-inducible factor (HIF-1α), Mothers against decapentaplegic (Smad-2), AKT, and apoptotic biomarkers like the Bax/Bcl2 ratio. When these antioxidants were combined, they had a stronger protective effect against cell death and mutations in all the organs studied.
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Lipopolysaccharide (LPS) has previously been implicated in insulin resistance by generating an innate immune response and activating inflammatory cascades. Many studies have discovered a relationship between high levels of serum LPS and the advancement of diabetic microvascular problems, indicating that LPS may play a role in the control of critical signaling pathways connected to insulin resistance. The current study focused on signaling pathways linked to insulin resistance and explored probable mechanisms of LPS-induced insulin resistance in a murine model. It next looked at the effects of burdock, bee pollen, and -lipoic acid on LPS-induced inflammation and autoimmune defects in rats. LPS intoxication was induced via ip injection for one week in a dose of 10 mg/kg followed by α-lipoic acid, Burdock and bee pollen in an oral treatment for one month. Following that, biochemical and molecular studies were performed. The RNA expression of the regulating genes STAT5A and PTEN was measured. In addition, ATF-4 and CHOP as autophagy biomarkers were also subjected to mRNA quantification. The results demonstrated a considerable improvement in the -lipoic acid, Burdock, and bee pollen treated groups via modifying oxidative stress indicators as well as molecular ones. Furthermore, glucose concentration in serum and α-amylase were also improved upon treatment with the superiority of α-lipoic acid for modulating all estimated parameters. In conclusion: the results declared in the current study suggested that α-lipoic acid could regulate insulin resistance signaling pathways induced by LPS intoxication.
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Autism spectrum disorder (ASD) is an extreme neuropsychotic disturbance with both environmental and genetic origins. Sodium propionate (PPA) a metabolic bioproduct of gut microbiota is well-thought-out as a successful autism animal model. Nevertheless, Liposomal drug delivery system possess the advantagous of biocompatibility, targeting organs, ability to carry large drug payloads and skipping macrophages for this purpose the current study was carried out to investigate the hypothesis that Calcium Voltage-Gated channel subunit alpha 1 C (CACNA1C) and glial fibrillary acidic protein (GFAP) signaling pathways crosstalk with the efficacy of Co-enzyme Q10 (Co-Q10) and liposomal loaded Co-enzyme Q10 (L Co-Q10) in PPA mediated autistic rat model. Autism was conducted by buffered PPA (500 mg/Kg b.wt) daily for 5 consecutive days subsequently treatment via Co-Q10 in a dose of (10 mg/kg b.wt) and L Co-Q10 (2 mg/kg b.wt) for four weeks then the autistic model was followed for signs of autism at different time intervals of (one, two and four weeks). The control, PPA intoxicated, and treated groups were subjected to behavioral tests (Y-Maze and open field), antioxidant analysis, gene expression analysis, and histological examination at different time intervals of the study. The results revealed that Co-Q10 and L Co-Q10 significantly elevated antioxidative stress biomarkers, comprising superoxide dismutase (SOD), glutathione (GSH), and total antioxidant capacity (TAC). In addition, they significantly ameliorated the oxidative stress biomarker malondialdehyde (MDA). Meanwhile, they significantly downregulated GFAP and CACNA1C mRNA gene expressions, Co-Q10 and LCo-Q10 showed improvement in almost brain regions post PPA histopathological alterations, even better results were manifested via LCo-Q10 groups. These results showed the superiority of LCo-Q10 over Co-Q10 in competing autism. In conclusion: The administration of anti-inflammatory and antioxidant agents such as Co-Q10 and L Co-Q10 may represent a promising strategy to counteract pathological behaviors in ASD model via targeting organs, increasing retention time, and reducing side effects.
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Engineered nanoparticles have been recently utilized in numerous domains particularly, silver nanoparticles (AgNPs). Nonetheless, the possible side effects resulting from AgNPs exposure are not fully clarified. The present study was designed to clarify the toxicity of AgNPs on lung tissue. Furthermore, therapeutic impact of Glycosmis pentaphylla (G. pentaphylla) and Casimiroa edulis (C. edulis) leaves extracts in addition to mucilage and protein (the purified compounds from C. edulis) was investigated against AgNPs induced pulmonary toxicity. Male Swiss albino mice were administered AgNPs orally in two different particle sizes (20 nm and 100 nm) for one month and was further treated via G. pentaphylla, C. edulis, mucilage and protein in a dose of 500 mg/ kg for three weeks. Biochemical, molecular, immunohistochemistry, and histopathological investigations were further assessed. An obvious alteration in oxidative stress biomarkers as well as mRNA gene expression of both survivin and matrix metalloproteinase (MMP-9) was recorded in AgNPs intoxicated group. In addition to, exploration of positive nuclei for Ki-67 was also observed upon AgNPs intoxication. Data declared a significant improvement in the assessed parameters upon G. pentaphylla, C. edulis, mucilage and protein treatment. In conclusion; G. pentaphylla and C. edulis extracts could be considered as a promising candidate as therapeutic regimen against pulmonary toxicity induced via AgNPs due to their enrichment with different active constituents. Practical applications: Due to the expansion of AgNPs applications, it is urgent to investigate their toxic impact associated with release of free silver ions. Different particle sizes of AgNPs can induce various alterations in cellular biochemical parameters, mRNA gene expression, histopathological and immunohistopathological examination. Herein, this natural products extracts are used for the first time as promising therapeutic regimen to ameliorate the toxic effect in AgNPs intoxicated lung tissue in mice model as a result of the bioactive metabolites, especially flavonoids and polyphenolic compounds.
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Rapid progress in nano-scales and nanostructure extremely altered the way of diagnosing or preventing numerous diseases. One of the most important nano-medicines used in cancer treatment and diagnosis is silver nanoparticles (AgNPs). Regardless of their extensive utilization, their prospective neurotoxicity wasn't studied yet. Herein, male Swiss Albino mice were intoxicated via two Nano-scales of AgNPs; (20 nm and 100 nm) for one month (100 mg/kg) then treated by leaves extracts of both Casimiroa edulis (C. edulis) and Glycosmis pentaphylla (G. pentaphylla), in addition to, mucilage and protein, the separated compounds from C. edulis fruits and seeds respectively in a dose of (500 mg/kg). Molecular, Biochemical and histopathological examinations were then conducted. Data recorded showed a significant elevation in hydrogen peroxide (H2O2) level and reduction in glutathione peroxidase (GPX) level post AgNPs intoxication. The oxidative stress occurred was modulated upon treatment regimens. Protein expression of C-reactive protein (CRP) showed a significant elevation and Molecular analysis recorded a significant up-regulation in the expression of both Bax and caspace-3 genes upon AgNPs intoxication in both particles size. On the contrary, both Bcl2 and P53 gene expression were shown to be significantly reduced. Treatment by C. edulis, G. pentaphylla, protein and mucilage extracts revealed modulation in apoptotic and pro-apoptotic biomarkers. Histopathological examination confirmed the obtained results. AgNPs exposure could induce neurotoxicity, genetic alternation and oxidative stress; the targeted extracts could be considered as a promising candidate in modulating apoptosis and neurotoxicity induced by AgNPs.
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BACKGROUND: Methotrexate (MX), a competitive inhibitor of dihydrofolate reductase, can inhibit DNA and RNA production and is a powerful anticancer agent widely utilized in clinical practice for treating nonneoplastic maladies, as psoriasis and rheumatoid arthritis; meanwhile, its probable prescription dose and interval of administration are strictly limited due to dose-related organ damage. Former studies verified that kidney, brain, liver, and lung harms are prospective obstacles of methotrexate administration. To understand the machinery of methotrexate-prompt toxicity, various mechanisms were investigated. The former is an autophagy defense mechanism; autophagy is a self-digesting mechanism responsible for the removal of damaged organelles and malformed proteins by lysosome. The contemporary article hypothesized that turmeric or its liposomal analog could defeat autophagy of MX-induced acute toxicity. Methotrexate, in a dose of 1.5 mg/kg, was administered intravenously followed by turmeric and liposomal turmeric treatment in a dose of 5 mg/kg for 30 days in rats. RESULTS: Increment in autophagy (AUTP) consent by MX administration was attenuated by concurrent treatment via turmeric and liposomal turmeric that was reliable on the alteration in apoptotic markers. The assembly of FOXO-3 in serum post methotrexate administration was suppressed by concurrent treatment via liposomal turmeric. Apoptosis/autophagic marker investigation was evaluated through the gene expression of Bax (BCL2-associated X protein)/Bcl2 (B-cell lymphoma 2)/P53 (tumor protein P53)/SiRT-1 (sirtuin silent mating-type information regulation 2 homolog 1) and FOXO-3 (forkhead box transcription factor-3)/ERDJ-4 (endoplasmic reticulum localized DnaJ homologs)/BNP (brain natriuretic peptide B) signaling. The cell death of all cells was categorized to achieve autophagy. Interestingly, Bax/Bcl2/P53/SiRT-1 signaling pathways were downregulated, contributing to inhibiting the initiation of autophagy. Meanwhile, FOXO-3/BNP/ERDJ-4 reduction-implicated noncanonical autophagy pathways were involved in methotrexate-induced autophagy, whereas this change was suppressed when turmeric was administered in liposomal form. CONCLUSION: These outcomes recommended that liposomal turmeric prevents MX-induced acute toxicity through its autophagy, antioxidant, and antiapoptotic properties.
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BACKGROUND: Mercuric chloride (HgCl3) is categorized as class II B hazardous metal that is present in many occupational and environmental conditions. In the meantime, Hg exists in the environment in such an abundant manner, it is virtually impossible for humans to avoid exposure to different forms of Hg. In addition to environmental exposure, individuals may be exposed to Hg from dental amalgams, medicinal treatments and dietary sources. Nevertheless, Liposomal drug delivery system is a promising era in the field of Nano-medicine and have the advantageous of increasing drug bioavailability and retention phenomena in addition to targeting organ for all mentioned the present study was designed to investigate the hypothesis that messenger RNA gene expression of Signal transducer and activator of transcription- 5 A (STAT-5A), Phosphatase and tensin homolog (PTEN), phosphoinositol kinase (PI3K) and alpha serine/threonine-protein kinase (AKT) can trigger HgCl3 induced nephrotoxicity post Ubidecarenone and liposomal Ubidecarenone therapy. METHODS: HgCl3 toxicity was induced in rats via a dose of 5 mg/kg BW for one week followed by Ubidecarenone and liposomal Ubidecarenone therapy in a dose of 10 & 3 mg/kg BW for one month, respectively. Then kidney function tests, Glutathione and gene expression for PI3K, AKT, PTEN and STAT-5A was investigated. RESULTS: HgCl3 intoxication significantly up regulated PI3K, AKT, PTEN and STAT-5A signaling pathways meanwhile, Ubidecarenone and liposomal- Ubidecarenone treatment significantly reduced PI3K, AKT, PTEN and STAT-5A gene expression post HgCl3 intoxication with the liposomal regimen revealing the most significant impact. Furthermore, renal toxicity was confirmed via monitoring urea and creatinine which were modulated post Ubidecarenone and liposomal-Ubidecarenone treatment. Wide evidence declared that mercuric S-conjugates of small endogenous thiols (such as Hcy, NAC and Cys) are probably the main transportable forms of Hg2+ to the kidneys thus reduced glutathione was investigated which reflected a significant down regulation post Hgcl3 toxicity. CONCLUSION: liposomal drug delivery system including liposomal-Ubidecarenone can be considered as a prospective candidate for treating HgCl3 renal toxicity via modulating STAT-5A, PTEN, PI3K and AKT signaling pathways and via increasing retention time, bioavailability, shielding from macrophage recognition and targeting organs.
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Mercurio , Fosfatidilinositol 3-Quinasas , Animales , Creatinina , Amalgama Dental , Glutatión , Humanos , Cloruro de Mercurio/toxicidad , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Mensajero/metabolismo , Ratas , Factor de Transcripción STAT5 , Transducción de Señal , Compuestos de Sulfhidrilo , Tensinas/metabolismo , Ubiquinona/análogos & derivados , UreaRESUMEN
Aluminum chloride (AlCl3) is commonly used in daily life; meanwhile, it is the potential etiology of various neurodegenerative as well as hepatorenal diseases. Therefore, the present study was carried out to investigate the correlation between AlCl3-induced biochemical alterations and the toxicity induced in various organs such as the brain, liver, and kidney. Male mice received AlCl3 in an oral dose of 50 mg kg-1 in addition to (50 mg) in drinking water for 2 weeks. Two weeks post-AlCl3 intoxication, the brain, liver, and kidney biochemical indices were assessed via molecular and western blot analysis. The results are as follows: AlCl3 intoxication induced a significant elevation in serum malondialdehyde in addition to a significant reduction in serum glutathione (GSH) and superoxide dismutase (SOD) levels. Brain ß-secretase (tubulin-binding protein) and tau proteins which are responsible for the synthesis of ß-amyloid protein that may interfere with neuronal communication in Alzheimer's disease (AD) were also upregulated; regarding hepatic function, AlCl3 elevated serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Moreover, it upregulated hepatic mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) protein expressions as well as renal kidney-inducible molecule-1 (KIM-1) which indicated the deleterious effect of AlCl3 on these organs. These results were confirmed by histopathological investigations. So, we hypothesize that acute AlCl3 administration is responsible for oxidative cell damage that interferes with brain function inducing ß-amyloid accumulation, Alzheimer's disease, and neurodegenerative damage as well as hepatorenal injuries.
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Secretasas de la Proteína Precursora del Amiloide , Proteínas Quinasas Activadas por Mitógenos , Aluminio , Cloruro de Aluminio , Compuestos de Aluminio/toxicidad , Animales , Cloruros/toxicidad , Hígado , Masculino , Ratones , Estrés OxidativoRESUMEN
Liposomal drug-delivery systems (LDDs) provide a promising opportunity to precisely target organs, improve drug bioavailability and reduce systemic toxicity. On the other hand, PI3K/Akt signaling pathways control various intracellular functions including apoptosis, invasion and cell growth. Hyper activation of PI3K and Akt is detected in some types of cancer that posses defect in PTEN. Tracking the crosstalk between PI3K/Akt, PTEN and STAT 5A signaling pathways, in cancer could result in identifying new therapeutic agents. The current study, identified an over view on PI3K/Akt, PTEN and STAT-5A networks, in addition to their biological roles in hepatocellular carcinoma (HCC). In the current study galactomannan was extracted from Caesalpinia gilliesii seeds then loaded in liposomes. Liposomes were prepared employing phosphatidyl choline and different concentrations of cholesterol. HCC was then induced in Wistar albino rats followed by liposomal galactomannan (700 ± 100 nm) treatment. Liver enzymes as well as antioxidants were assessed and PI3K/Akt, PTEN and STAT-5A gene expression were investigated. The prepared vesicles revealed entrapment efficiencies ranging from 23.55 to 69.17%, and negative zeta potential values. The optimum formulation revealed spherical morphology as well as diffusion controlled in vitro release pattern. Liposomal galactomannan elucidated a significant reduction in liver enzymes and MDA as well as PI3K/Akt, PTEN and STAT 5A gene expression. A significant elevation in GST and GSH were deduced. In conclusion, Liposomal galactomannan revealed a promising candidate for HCC therapy.
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Potential of Casimiroa edulis and Glycosmis pentaphylla leaves extracts were investigated against the effect of two different particle sizes of silver nanoparticles induced toxicity in mice. Mice received silver nanoparticles (AgNPs) (100 mg/kg) with 20 and 100 nm for four weeks followed by daily oral dose of extracts (500 mg/kg) for three weeks. C. edulis leaves identified fourteen phenolic compounds while, G. pentaphylla leaves identified, twelve phenolic compounds. Additionally, biochemical, genotoxicity, mutagenicity, and histopathological investigations were carried out, revealed that liver function activities, lipid profile, hydrogen peroxide, and C-reactive protein were significantly elevate post AgNPs exposure. While, superoxide dismutase, glutathione-S-transferases, and glutathione peroxidase significantly reduce. A marked amelioration in all detected biomarkers, improved histopathological changes and repair DNA damage after treated with C. edulis and G. pentaphylla leaves extracts. These extracts are used for the first time as promising candidate therapeutic agents against toxicity induced by AgNPs. PRACTICAL APPLICATIONS: The potential applications of AgNPs make it necessary to investigate the possible toxicity associated with release of free silver ions in the biological system. AgNPs of varying particle sizes had toxic effects as evidenced by alterations in some cellular biochemical parameters, genotoxicity, mutagenicity, and histopathological indices on mice. Casimiroa edulis and Glycosmis pentaphylla leaves extracts are used for the first time as promising candidate therapeutic, where they are able to ameliorate the toxicity induced via AgNPs and record vacillate percentage of improvement in the selected biomarkers, as a result of the bioactive secondary metabolites especially flavonoids and other polyphenolic compounds.
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OBJECTIVES: Type 2 diabetes mellitus (DMT2) is contributed to dual interactions between environmental factors and certain genetic factors. This impressed a great need for novel treatment strategy. Nevertheless, Hyssopus officinalis (H. officinalis) as a terrestrial herb is considered to be an important source of natural antioxidants, it could be assessed as an anti-hyperglycemic agent. METHODS: In the current study, HPLC identified the active constitutes of H. officinalis, including total polyphenols, and flavonoids. Type 2 diabetes mellitus was induced in male Wistar albino rats via a single ip dose of streptozotocin (STZ) (35 mg/kg BW). One week post diabetes induction, rats were administrated H. officinalis (500 mg/ kg BW) orally for one month. Molecular analysis was assessed to investigate the efficiency of H. officinalis on modulating ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1) genes, in addition to apoptotic biomarkers, glycogen synthase kinase-3ß (GSK-3ß) and cellular oncogene-fos (C-fos) genes. Furthermore, inflammatory biomarkers, nuclear factor kappa-B (NF-κB) and tumor necrosis factor-α (TNF-α) gene expression were also assessed. RESULTS: H. officinalis alcoholic extract declared the presence of polyphenols as gallic acid and flavonoids as quercetin in addition to many active constituents. Apigenin-7-glucoside and Chlorgenic acid were the most common constituents in the extract. RT-PCR results declared a significant up-regulation in mRNA gene expression of ABCA1 and ABCG1 upon H. officinalis treatment. Meanwhile, C-fos gene expression recorded a slight down-regulation. Gene expression of apoptotic biomarker GSK-3ß demonstrated a significant down regulation as well as inflammatory biomarkers NF-κB and TNF-α. CONCLUSION: From the data recorded, it could be concluded that H. officinalis exerts a great hypoglycemic potential via modulating C-fos, GSK-3ß, NF-κB, TNF-α, ABCA1 and ABCG1 gene expression and signaling pathways and could be considered as an effective candidate for DMT2 treatment.
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The wide application of nanotechnology merits the need to clarify their nanotoxicity. In vivo studies have raised concerns about the toxicity of titanium dioxide nanoparticles (TiO2 NPs), but there are limited data on chromosomal abnormalities induced in hepatic tissue. In this article, the toxicity of three IP doses of TiO2 NPs (80 nm) (50, 250, and 500 mg/kg) through three time intervals (up to 7, 15, and 45 days) on liver tissue was assessed. Hepatic catalase (CAT), glutathione (GSH), nitric oxide (NOx), and malondialdehyde (MDA) levels varied with the administered dose and exposure time of TiO2 NPs. As a result, TiO2 NPs caused a statistically significant decrease in hepatic CAT and GSH activities and a significant alleviation in MDA and NOx levels (p < 0.05), suggesting that the liver exposed to these various doses of TiO2 NPs suffered from severe oxidative stress. The extent of depletion of antioxidant enzymes and the elevation of MDA and NOx in the liver exposed to the highest dose and duration of TiO2 NPs 500 mg for 45 days was the greatest, suggesting that the toxicity might be dose and time dependent. Further, C-reactive protein (CRP) as an inflammatory marker was also alleviated, in addition to the apparent chromosomal aberration and liver pathologies including necrotic and fibrotic hepatocytes after exposure to 250 and 500 mg/kg of TiO2 NPs for 14 and 45 days that were deduced. Hence, nanotechnology-based industries are growing rapidly leading to large-scale production of engineered nanoparticles. They contribute to increased chances of human NPs exposure and health risk.
Asunto(s)
Nanopartículas del Metal , Nanopartículas , Proteína C-Reactiva/metabolismo , Aberraciones Cromosómicas/inducido químicamente , Humanos , Hígado/metabolismo , Nanopartículas del Metal/toxicidad , Estrés Oxidativo , Titanio/toxicidadRESUMEN
Nano-medicine can passively accumulate in chronic inflammatory tissues via the enhanced permeability and retention phenomenon, or by being conjugated with a ligand that can bind to receptors over expressed by cells inside chronic inflammatory tissues, contributing to reduced systemic side-effects and increased efficacy. This article highlights the utilization of nanomedicine for potential treatment of rheumatoid arthritis. Rheumatoid arthritis was induced in rat model via 2 weeks intradermal injection of pristane at the base of the tail in a daily dose of 150 µl. Susceptible rat strains developed severe arthritis with a sudden onset 3 weeks post pristane injection. Three weeks post pristane administration; rats were treated intravenously with glutathione or liposomal-glutathione in a dose of 5 mg/kg daily for 30 days. Concomitant supplementation with the aforementioned antioxidants effect on proinflammatory marker C-reactive protein (CRP) was assessed. On the other hand, oxidative stress biomarker malondialdehyde (MDA) and rheumatoid factor (RF) compared with pristane treated group was also investigated. The results elucidated that glutathione and liposomal -glutathione significantly reduced rheumatoid factor, malondialdehyde and C-reactive protein levels with the superiority of liposomal -glutathione in this side reflecting its pronounced effect as anti-rheumatoid agent.
RESUMEN
The expedient fungi Candida albicans (C. albicans) is able to thrive in many host niches including blood stream, skin, mucosal surfaces, and different body organs. Herein, the assessment of novel synthesized pyrimidine derivatives as anti fungal agent was investigated. Female albino mice were injected intraperitoneally by C. albicans (1.5 × 106 CFU). infected Mice then subjected to treatment with two different doses which was low (50 mg/kg) and high one (200 mg/kg) of diflucan in addition to the newly synthestic compounds (2-(4- (Pyridine- 2- yl) aminosulfonyle phenylamino) - 6 -(naphthalene-2- yl)-4-(pyridine-2- yl) n - 3 carbonitril) and (2-(4-(Pyrimidine-2- yl) aminosulfonyle phenylamino)- 6 -(naphthalene-2- yl)- 4 -(pyridine-2- yl) pyridine-3- carbonitril) donated as (C1 & C2, respectively). Three weeks later gene expression of renal alpha smooth muscle actin (α-SMA) and of cyclooxygenase-2 (COX-2) protein expression were assessed as well as serum malondialdehyde (MDA) and total antioxidant capacity in both kidney and brain tissues. Furthermore, acetylcholinestrase activity was assessed. Candida albicans significantly elevated serum MDA. On the other hand, C. albicans injection revealed a significantly reduction in total antioxidant capacity in kidney as well as in brain tissue. Furthermore, acetylcholine assessment declared a significant elevation. All biochemical parametersÛ¥ upset were modulated upon new synthesized compounds treatment. Molecular analyses declared a significant down - regulation in renal α -smooth muscle actin gene expression in addition to, a significant down- regulation in COX-2 protein expression. From data recorded, it could be concluded that, C2 in a dose 200 mg ∕kg noticeably declared a significant effect comparing with the other treated groups revealing its promising effect as anti-fungal agent.