RESUMEN
The expanding uses of carbon nanotubes (CNTs) in industry and medicine have raised concerns about their toxicity on human and animal health. CNTs, including multi-walled nanotubes (MWCNTs), have been reported to induce immunotoxic, inflammatory, and oxidative effects. Quercetin is a natural flavonoid present in many vegetables and fruits and has immunomodulatory, anti-inflammatory, and antioxidant properties. Herein, we investigated the protective effects of quercetin on pristine MWCNTs-induced immunotoxicity in mice. In comparison with two doses of MWCNTs, high doses [0.5 mg/kg body weight (BW), once intraperitoneally (IP)] caused higher immunotoxic, inflammatory, and oxidative effects than low doses (0.25 mg/kg BW, once IP). Administration of quercetin (30 mg/kg BW, IP for 2 weeks) relieved these deleterious effects as evidenced by (1) reduced spleen weight, (2) increased number of total leukocytes, lymphocytes, and neutrophils, (3) elevated serum levels of IgM, IgG, and IgA, (4) decreased lipid peroxide malondialdehyde levels and increased levels of antioxidant markers reduced glutathione, superoxide dismutase, and catalase in the spleen, (5) decreased concentrations and mRNA levels of inflammatory markers tumor necrosis factor-alpha (TNFα), interleukin 1 beta (IL1ß), and IL6 in the spleen, (6) downregulated expression of immunomodulatory genes transforming growth factor-beta (TGFß), cyclooxygenase2 (COX2), and IL10, and (7) regenerative histological changes as indicated by decreased mononuclear cell infiltration, minimized degenerative changes and restored lymphocytes depletion in the spleen. These results infer that quercetin can ameliorate MWCNTs-induced immunotoxic, inflammatory, and oxidative effects.
Asunto(s)
Nanotubos de Carbono , Quercetina , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Glutatión/metabolismo , Ratones , Nanotubos de Carbono/toxicidad , Estrés Oxidativo , Quercetina/farmacologíaRESUMEN
Zinc oxide nanopartciles (ZnONPs) involved in advanced technologies, and their wide-scale use in consumer market makes human beings more prone to the exposure to ZnONPs. The present study was undertaken to evaluate amelioration of ZnONP-induced toxicities with querectin in male albino rats. ZnONPs-treated rats showed a significant decrease in sperm cell count, sperm motility, live and normal sperms, as well as serum testosterone level. Severe histopathological damage with a significant increase in lipid peroxidation and a decrease in antioxidant enzymes activity and the GSH level were observed in the affected testis. Relative quantitative polymerase chain reaction results showed a significant decrease in antioxidant enzymes (superoxide dismutase and catalase) and a significant decrease in 3ß-HSD, 17ß-HSD, and Nr5A1 transcripts. Rats-administered querectin along with ZnONPs showed less toxic effects on all studied reproductive traits and mRNA transcripts. Our results suggest that querectin is beneficial for preventing or ameliorating ZnONP reproductive toxicities in males.
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Antioxidantes/farmacología , Nanopartículas del Metal/toxicidad , Quercetina/farmacología , Espermatozoides/efectos de los fármacos , Testículo/efectos de los fármacos , Óxido de Zinc/toxicidad , 17-Hidroxiesteroide Deshidrogenasas/genética , 17-Hidroxiesteroide Deshidrogenasas/metabolismo , 3-Hidroxiesteroide Deshidrogenasas/genética , 3-Hidroxiesteroide Deshidrogenasas/metabolismo , Administración Oral , Animales , Catalasa/genética , Catalasa/metabolismo , Regulación de la Expresión Génica , Glutatión Peroxidasa/genética , Glutatión Peroxidasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Estrés Oxidativo/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Recuento de Espermatozoides , Motilidad Espermática/efectos de los fármacos , Espermatozoides/citología , Espermatozoides/metabolismo , Factor Esteroidogénico 1/genética , Factor Esteroidogénico 1/metabolismo , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Testículo/citología , Testículo/metabolismo , Testosterona/sangre , Óxido de Zinc/antagonistas & inhibidoresRESUMEN
Gibberellic acid (GA3) was used extensively unaware in agriculture in spite of its dangerous effects on human health. The current study was designed to investigate the ameliorative effects of the co-administration of phycocyanin with GA3 induced oxidative stress and histopathological changes in the liver. Forty male albino rats were randomly divided into four groups. Group I (control group) received normal saline for 6 weeks, Group II (GA3 treated group) received 3.85 mg/kg body weight GA3 once daily for 6 weeks, Group III (phycocyanin treated group) received Phycocyanin 200 mg/kg body weight/day for 6 weeks orally dissolved in distilled water and Group IV was treated with GA3 and phycocyanin at the same doses as groups 2 and 3. All treatments were given daily using intra-gastric intubation and continued for 6 weeks. Our results revealed significant downregulation of antioxidant enzyme activities and their mRNA levels (CAT, GPx and Cu-Zn, SOD) with marked elevation of liver enzymes and extensive fibrous connective tissue deposition with large biliary cells in hepatic tissue of GA3 treated rats, while treatment with phycocyanin improved the antioxidant defense system, liver enzymes and structural hepatocytes recovery in phycocyanin treated group with GA3. These data confirm the antioxidant potential of Phycocyanin and provide strong evidence to support the co-administration of Phycocyanin during using GA3.
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Giberelinas/toxicidad , Hígado/efectos de los fármacos , Ficocianina/farmacología , Animales , Supervivencia Celular/efectos de los fármacos , Hígado/enzimología , Hígado/metabolismo , Masculino , Estrés Oxidativo/efectos de los fármacos , RatasRESUMEN
BACKGROUND: The potential involvement of type 2 diabetes mellitus (T2DM) as a risk factor for colon cancer (CC) has been previously reported. Epigenetic changes, such as deregulation of long non-coding RNA (lncRNA) and microRNA (miR), have been linked to the advancement of CC; however, the effects of high glucose levels on their deregulation and, in turn, colon cancer remain unexplored. METHODS: Fifty patients had a dual diagnosis of CC and T2DM, and 60 patients with CC without diabetes mellitus were included in the study. qRT-PCR was used to examine the expression of lncRNA ANRIL and miR-186-5p in tissue samples. ANRIL, miR-186-5p, and their downstream target genes HIF-1α, PFK, HK, Bcl-2, and Bax were also determined in CC cell lines under various glucose conditions. Glucose uptake, lactate production and cells proliferation were estimated in CC cell lines. RESULTS: A significant upregulation of ANRIL expression levels (p<0.001) and a significant downregulation of miR-186-5p expression (p<0.001) in diabetic colon cancer specimens compared to those in non-diabetic colon cancer group were observed. MiR-186-5p expression levels were inversely correlated with ANRIL expression levels, blood glucose levels and HbA1c%. Concerning in vitro model, a significant upregulation of ANRIL, downregulation of miR-186-5p, upregulation of HIF-1α, glycolytic enzymes and activation of antiapoptotic pathway was detected in higher glucose concentrations than lower one. There was a significant increase of glucose uptake, lactate accumulation and proliferation of the Caco2 and SW620 cell lines in a dose dependent manner of glucose concentrations. Moreover, a significant positive correlation between glucose uptake and ANRIL expression was shown. CONCLUSIONS: A high-glucose environment can increase the tumor-promoting effect of ANRIL. ANRIL can promote glucose metabolism and colon cancer proliferation by downregulating miR-186-5p with subsequent upregulation of glycolysis enzymes expression and inhibition of apoptosis.
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Proliferación Celular , Neoplasias del Colon , Diabetes Mellitus Tipo 2 , Glucosa , MicroARNs , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , Neoplasias del Colon/metabolismo , Neoplasias del Colon/genética , Neoplasias del Colon/patología , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/genética , MicroARNs/genética , Masculino , Femenino , Persona de Mediana Edad , Pronóstico , Glucosa/metabolismo , Regulación Neoplásica de la Expresión Génica , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Estudios de Casos y Controles , Apoptosis , Estudios de Seguimiento , Células Tumorales Cultivadas , Tasa de Supervivencia , AncianoRESUMEN
Introduction: Glucagon-like peptide -1 (GLP-1) is released by intestinal cells to stimulate glucose-dependent insulin release from the pancreas. GLP-1 has been linked to ameliorating obesity and/or diabetic complications as well as controlling reproductive function. Liraglutide is a GLP-1 receptor agonist (GLP-1RA) with 97% homology with GLP-1. The main objective of this study was to investigate the ameliorative role of liraglutide in diabetic-induced reproductive dysfunction in male rats. Methods: Rats were randomly allocated into 3 groups; a control group, a diabetic group, and a liraglutide-treated diabetic group. Results: In the diabetic group, a significant increase in BMI, FBG, HbA1c, HOMA-IR, TC, TAG, LDL, IL6, TNFα, and MDA, as well as decreased serum insulin, HDL, GSH, total testosterone, LH, and FSH, were shown compared to the control group. Furthermore, A significant downregulation in relative hypothalamic gene expression of GLP-1R, PPAR-α, PGC-1α, kiss, kiss1R, leptin, leptin R, GnRH GLP-1R, testicular PGC-1α, PPARα, kiss1, kiss1R, STAR, CYP17A1, HSD17B3, CYP19A, CYP11A1, and Smad7, as well as upregulation in hypothalamic GnIH and testicular TGF- ß and Smad2 expression, were noticed compared to the control group. Liraglutide treatment significantly improved such functional and structural reproductive disturbance in diabetic rats. Conclusion: GLP-1RAs ameliorated the deleterious effects of diabetes on reproductive function by targeting GLP-1/leptin/kiss1/GnRH, steroidogenesis, and TGF- ß/Smad pathways.
RESUMEN
The nano-sized iron oxide (Fe2O3-NPs) is one of the most used engineered nanomaterials worldwide. This study investigated the efficacy of natural polyphenol resveratrol (RSV) (20 mg/kg b.wt, orally once daily) to alleviate the impaired sperm quality and testicular injury resulting from Fe2O3-NPs exposure (3.5 or 7 mg/kg b.wt, intraperitoneally once a week) for eight weeks. Spermiograms, sexual hormonal levels, oxidative stress indicators, and lipid peroxidation biomarker were assessed. Moreover, the steroidogenesis-related genes mRNA expressions were evaluated. The results showed that RSV substantially rescued Fe2O3-NPs-mediated sperm defects. Additionally, the Fe2O3-NPs-induced depressing effects on sperm motility and viability were markedly counteracted by RSV. Moreover, RSV significantly restored Fe2O3-NPs-induced depletion of testosterone, follicle-stimulated hormone, luteinizing hormone, and testicular antioxidant enzymes but reduced malondialdehyde content. Furthermore, the Fe2O3-NPs-induced downregulation of steroidogenesis-related genes (3 ß-HSD, 17 ß-HSD, and Nr5A1) was significantly counteracted in the testicular tissue of RSV-treated rats. These findings concluded that RSV could limit the Fe2O3-NPs-induced reduced sperm quality and testicular injury most likely via their antioxidant activity and steroidogenesis-related gene expression modulation.
Asunto(s)
Semen , Motilidad Espermática , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Compuestos Férricos , Masculino , Estrés Oxidativo , Ratas , Resveratrol/farmacología , Testículo/metabolismo , Testosterona/metabolismoRESUMEN
The present experiment was performed to investigate the toxic impact of thiacloprid (TH) on the brain of developing chicken embryos and also to measure its influence on the behavioral responses of hatchlings. The role of chicoric acid (CA) and rosmarinic acid (RA) in modulating the resulted effects was also investigated. The chicken eggs were in ovo inoculated with TH at different doses (0.1, 1, 10, and 100 ug/egg). TH increased the mortality and abnormality rates and altered the neurochemical parameters of exposed embryos dose-dependently. TH also decreased the brain level of monoamines and amino acid neurotransmitters and decreased the activities of acetylcholine esterase (AchE) and Na+/K+-ATPase. The brain activity of catalase (CAT) and superoxide dismutase (SOD) was diminished with downregulation of their mRNA expressions in the brain tissue. When TH was co-administered with CA and RA, the toxic impacts of the insecticide were markedly attenuated, and they showed a complementary effect when used in combination. Taken together, these findings suggested that TH is neurotoxic to chicken embryos and is possibly neurotoxic to embryos of other vertebrates. The findings also demonstrated the antioxidant and neuroprotective effects of CA and RA. Based on the present findings, the CA and RA can be used as invaluable ameliorative of TH-induced toxicity.
RESUMEN
Recently, we reported that quercetin (Que) could alleviate immunotoxicity induced by pristine multi-walled carbon nanotubes (MWCNTs) in mice. In the present study, we explored whether Que could also relieve MWCNTs-induced neurotoxicity. MWCNTs injection induced a dose-dependent neurotoxic effect in mice as evidenced by increased oxidative stress, inflammation, and pyroptosis in the brain. However, treatment with Que ameliorated MWCNTs-induced neurotoxicity as revealed by 1) elevated acetylcholinesterase (AChE) activity, 2) reduced lipid peroxidation biomarker malondialdehyde (MDA), 3) improved antioxidant status as indicated by increased levels of reduced glutathione (GSH) and activities of superoxide dismutase (SOD), catalase (CAT), as well as upregulated expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) genes, 4) decreased levels and expression of inflammatory biomarkers [nitric oxide (NO), interleukin 1 beta (IL1ß), tumor necrosis factor-alpha (TNFα), and nuclear factor kappa B (NF-κB)], 5) downregulated expression of pyroptosis-related genes [nod-like receptor protein inflammasome 3 (Nlrp3) and caspase 1 (Casp1)] but with no effect on the apoptotic Casp3 gene, 6) minimized axonal degeneration and number of microglia in the cerebral medulla, and 7) diminished the number of degenerated neurons in hippocampus and cerebellum. Taken together, Que could ameliorate MWCNT-induced neurotoxicity through antioxidant, anti-inflammatory, and anti-pyroptotic mechanisms.
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Nanotubos de Carbono , Quercetina , Acetilcolinesterasa/metabolismo , Animales , Antioxidantes/metabolismo , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Ratones , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Nanotubos de Carbono/toxicidad , Estrés Oxidativo , Piroptosis , Quercetina/farmacología , Quercetina/uso terapéuticoRESUMEN
Merkel cell polyomavirus (MCV) is the causative agent for the majority of Merkel cell carcinoma (MCC) cases. Polyomavirus-associated MCC (MCCP) is characterized by the integration of MCV DNA into the tumor genome and a low tumor mutational burden. In contrast, nonviral MCC (MCCN) is characterized by a high tumor mutational burden induced by UV damage. Since the discovery of MCV, much work in the field has focused on understanding the molecular mechanisms of oncogenesis driven by the MCV tumor (T) antigens. Here, we review our current understanding of how the activities of large T (LT) and small T (ST) promote MCC oncogenesis in the absence of genomic instability. We highlight how both LT and ST inhibit tumor suppressors to evade growth suppression, an important cancer hallmark. We discuss ST interactions with cellular proteins, with an emphasis on those that contribute to sustaining proliferative signaling. Finally, we examine active areas of research into open questions in the field, including the origin of MCC and mechanisms of viral integration.
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Carcinogénesis/genética , Carcinoma de Células de Merkel/virología , Poliomavirus de Células de Merkel/genética , Antígenos Virales de Tumores/genética , Transformación Celular Neoplásica , Virus ADN , Genoma Viral , Inestabilidad Genómica , Humanos , Neoplasias Cutáneas/virología , Infecciones Tumorales por Virus/virología , Integración ViralRESUMEN
BACKGROUND: Enlarged facial pores are becoming a matter of cosmetic concern. Injections of (botulinum toxin type A) have an increasing popularity among cosmetic procedures. OBJECTIVE: To determine the efficacy and safety of intradermal injection of botulinum toxin in treatment of excess sebum secretion and enlarged facial pores. MATERIALS AND METHODS: This split face-controlled pilot study was conducted on 20 patients with enlarged facial pores and seborrhea. One cheek was treated by intradermal injection of botulinum toxin, and the other was injected by saline. Patient assessment was performed after 1 and then after 4 months. RESULTS: At 1-month assessment, both sides showed significant reduction in their sebum and pore scores (p = .001), with significantly more improvement on the botulinum toxin-treated side. Dermoscopy documented a significant decrease in the average size of facial pores (p < .001), and the OCT demonstrated a significant increase in the dermal thickness (p < .001) with non-significant deference between both sides. Four months after treatment, the botulinum toxin-treated side maintained its improvement in both scores. CONCLUSION: Intradermal injection of botulinum toxin is an effective and safe procedure for the management of excess sebum and facial pores with acceptable results lasting for an average of 4 months.
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Toxinas Botulínicas Tipo A , Dermatitis Seborreica , Fármacos Neuromusculares , Toxinas Botulínicas Tipo A/uso terapéutico , Humanos , Hipertrofia , Inyecciones Intradérmicas , Proyectos Piloto , SeboRESUMEN
Autophagy is a key metabolic process where cells can recycle its proteins and organelles to regenerate its own cellular building blocks. Chemotherapy is indispensable for cancer treatment but associated with various side-effects, including organ damage. Stem cell-based therapy is a promising approach for reducing chemotherapeutic side effects, however, one of its main culprits is the poor survival of transplanted stem cells in damaged tissues. Here, we aimed to test the effects of activating autophagy in adipose-derived mesenchymal stem/stromal cells (ADSCs) on the survival of ADSCs, and their therapeutic value in cisplatin-induced liver injury model. Autophagy was activated in ADSCs by rapamycin (50 nM/L) for two hours before transplantation and were compared to non-preconditioned ADSCs. Rapamycin preconditioning resulted in activated autophagy and improved survival of ADSCs achieved by increased autophagosomes, upregulated autophagy-specific LC3-II gene, decreased protein degradation/ubiquitination by downregulated p62 gene, downregulated mTOR gene, and finally, upregulated antiapoptotic BCL-2 gene. In addition, autophagic ADSCs transplantation in the cisplatin liver injury model, liver biochemical parameters (AST, ALT and albumin), lipid peroxidation (MDA), antioxidant profile (SOD and GPX) and histopathological picture were improved, approaching near-normal conditions. These promising autophagic ADSCs effects were achieved by modulation of components in TGF-ß1/Smad and PI3K-AKT signaling pathways, besides reducing NF-κB gene expression (marker for inflammation), reducing TGF-ß1 levels (marker for fibrosis) and increasing SDF-1 levels (liver regeneration marker) in liver. Therefore, current results highlight the importance of autophagy in augmenting the therapeutic potential of stem cell therapy in alleviating cisplatin-associated liver damage and opens the path for improved cell-based therapies, in general, and with chemotherapeutics, in particular.
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Autofagia , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/prevención & control , Células Madre Mesenquimatosas/citología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Smad/metabolismo , Trasplante de Células Madre/métodos , Factor de Crecimiento Transformador beta1/metabolismo , Animales , Antineoplásicos/toxicidad , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/patología , Cisplatino/toxicidad , Femenino , Masculino , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , Ratas , Ratas Sprague-Dawley , Proteínas Smad/genética , Factor de Crecimiento Transformador beta1/genéticaRESUMEN
BACKGROUND: Nasopharyngeal carcinoma (NPC) is the most common cancer arising from the nasopharynx with a poor prognosis. Targeting immune checkpoint is one of the new promising lines in cancer treatment. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-ligand 1 (PD-L1) are immune checkpoints that regulate T-cell immune function. AIM: This work aimed to assess the immunohistochemical expression of PD-L1 and CTLA-4 in NPC and their ability to predict survival and response therapy and to check their validity as immunotherapy targets. Twenty-six cases of NPC were studied by immunohistochemistry for PD-L1 and CTLA-4 and by nested polymerase chain reaction followed by DNA sequencing for the presence of EBNA-1 gene of Epstein-Barr virus (EBV). All investigated cases were diagnosed and treated in the Zagazig University Hospital in the period from August 2015 to July 2018. EBNA-1 gene was identified in 84.6% of the cases. Whereas the expression of PD-L1 was noted in 46.2% of all cases studied, 54.6% of EBV-associated NPCs were found to express PD-L1. There was a significant association between PD-L1 expression and the advanced stage of the tumor (P<0.001). CTLA-4 expression was observed in 88.4% of all NPC cases as cytoplasmic staining in both tumor cells and tumor-infiltrating lymphocytes. CTLA-4 expression in lymphocytes was associated with the presence of EBV. A significant association was detected between CTLA-4 and tumor-infiltrating lymphocyte expression on one side and the stage of the tumor on the other. High expression of CTLA-4 was significantly associated with disease progression and worse overall survival. CONCLUSION: PD-L1 and CTLA-4 are adverse prognostic markers in NPC. The authors propose that targeted therapy against PD-L1 and CTLA-4 will be a hopeful therapy for cases of NPC with resistance to concurrent chemoradiation treatment in Egypt, especially EBV-associated cases.
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Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/metabolismo , Antígeno CTLA-4/metabolismo , Infecciones por Virus de Epstein-Barr/metabolismo , Herpesvirus Humano 4/fisiología , Inhibidores de Puntos de Control Inmunológico/metabolismo , Linfocitos Infiltrantes de Tumor/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/mortalidad , Antígenos Nucleares del Virus de Epstein-Barr/genética , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo/inmunología , Neoplasias Nasofaríngeas/inmunología , Neoplasias Nasofaríngeas/mortalidad , Estadificación de Neoplasias , Pronóstico , Análisis de SupervivenciaRESUMEN
Silver nanoparticles (AgNPs) have been widely produced for different industrial purposes. Recently, biogenic synthesis of AgNPs has emerged although the extent of effects from exposure, oral exposure in particular, to nanomaterials synthesized in such a manner remains elusive. The main objective of this study was to evaluate the effects of oral administration of a dose of 50 mg/Kg body weight AgNPs biosynthesized in baker's yeast (Saccharomyces cerevisiae) over a period of eight weeks on the reproductive performance and the possibility of a protective effect through co-administration of morin. Forty-eight male Sprague-Dawley rats were used in four experimental groups (control, morin-treated group, AgNP-treated, and AgNP + morin co-treatment). AgNPs produced no significant alteration in daily food intake or body weight. Both the absolute and relative testicular weights were significantly reduced but not the epididymal weight. Also, serum levels of urea, creatinine, uric acid, and liver enzymes were significantly elevated. Furthermore, AgNPs significantly downregulated the hypothalamic-pituitary-gonadal axis. This corresponds to lower motility and viability percent, reduced sperm concentration, and a higher abnormality ratio as well as a prominent alteration in the blood-testis barrier (BTB) and testicular histology and induction of testicular apoptosis and oxidative stress. The supplementation of morin evidently restored most of the reproductive characters to its physiological range. We can conclude that exposure to the biologically synthesized AgNPs for an extended period of time has proven to be a health risk that can be ameliorated via oral administration of some bioactive agents including morin.
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Antioxidantes/farmacología , Flavonoides/farmacocinética , Nanopartículas del Metal/toxicidad , Plata/toxicidad , Administración Oral , Animales , Apoptosis , Barrera Hematotesticular , Epidídimo , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Recuento de Espermatozoides , Espermatozoides/efectos de los fármacos , Testículo/efectos de los fármacosRESUMEN
The present study aimed to examine the ameliorative effects of morin and rutin on the reproductive toxicity induced by titanium dioxide nanoparticles (TiO2NPs) in male rats. A total of seventy adult male Sprague-Dawley rats were randomly divided into seven groups, each comprising ten rats. Nanoreprotoxicity was induced by treating rats with TiO2NPs at a dosage of 300 mg/kg body weight for 30 days. Morin (30 mg/kg body weight) and rutin (100 mg/kg body weight) were co-administered with or without TiO2NPs to rats either individually or combined. Only distilled water was administered to the control group. The results showed that TiO2NPs enhanced oxidative stress, indicated by reduced levels of antioxidants such as superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) in testicular tissues, and increased levels of the lipid peroxidation marker malondialdehyde (MDA). TiO2NPs significantly reduced the levels of sex hormones (testosterone, FSH, and LH), reduced sperm motility, viability, and sperm cell count, and increased sperm abnormalities, in addition to damaging the testicular histological architecture. TiO2NPs resulted in the downregulation of 17ß-HSD and the upregulation of proapoptotic gene (Bax) transcripts in the testicular tissues. Conversely, morin and/or rutin had a protective effect on testicular tissue. They effectively counteracted TiO2NP-induced oxidative damage and morphological injury in the testis by conserving the endogenous antioxidant mechanisms and scavenging free radicals. Thus, we suggest that morin and rutin could be used to alleviate the toxicity and oxidative damage associated with TiO2NP intake.
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Antioxidantes/farmacología , Flavonoides/farmacología , Nanopartículas/toxicidad , Rutina/farmacología , Titanio/toxicidad , Animales , Antioxidantes/metabolismo , Catalasa/metabolismo , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Recuento de Espermatozoides , Motilidad Espermática/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Testículo/efectos de los fármacos , Testosterona/metabolismoRESUMEN
OBJECTIVES: Endosulfan is a broad-spectrum organochlorine insecticide that has been commercially in use for decades to control insect pests and has been found to pollute the aquatic environment. The current study was carried out to investigate the toxic effects of endosulfan, an organochlorine pesticide, on Nile tilapia (Oreochromis niloticus), a freshwater fish, and the alleviating effects of lycopene on the induced toxicity. METHODS: Four treatment groups of fish were investigated (3 replicates of 15 fish for each group): (1) a control group, (2) a group exposed to endosulfan, (3) a group that was fed on a basal diet supplemented with lycopene, and (4) a group that was fed on a basal diet supplemented with lycopene and exposed to endosulfan. The experiment was carried out over a 4-week period. RESULTS: Endosulfan negatively affected liver function, including liver enzymes and plasma proteins. Endosulfan affected blood parameters of fish and reduced the counts of red blood cells (RBCs) and white blood cells (WBCs), as well as affected immunological parameters. Endosulfan caused oxidative stress, as it decreased the values of antioxidants catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPX), and glutathione (GSH), and increased the level of lipid peroxide malondialdehyde (MDA). Additionally, endosulfan increased cytochrome P450 (CYP450) levels, while it decreased glutathione S-transferase (GST) mRNA transcript levels and distorted the normal histological structure of the liver, gills, and spleen of affected fish. Conversely, lycopene partially restored the aforementioned parameters when administered concomitantly with endosulfan. CONCLUSION: The results showed the beneficial effects of supplementing fish diets with lycopene as a natural antioxidant for ameliorating the toxicity caused by endosulfan.
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Cíclidos/metabolismo , Endosulfano/toxicidad , Branquias , Hígado , Licopeno/farmacología , Bazo , Animales , Antioxidantes/farmacología , Proteínas Sanguíneas/metabolismo , Suplementos Dietéticos , Egipto , Branquias/efectos de los fármacos , Branquias/metabolismo , Insecticidas/toxicidad , Hígado/efectos de los fármacos , Hígado/metabolismo , Estrés Oxidativo/efectos de los fármacos , Bazo/efectos de los fármacos , Bazo/metabolismoRESUMEN
AIMS: We investigate the consequence of adjuvant anastrozole (ANA) in monotherapy or associated with biochanin A (BCA) in ovariectomized (OVX) rat model and the degree of developing bone loss in both conditions. MATERIALS AND METHODS: Sixty female rats were assigned to six groups. Five groups were bilaterally OVX, and one was sham operated. The five groups were; ANA group (0.5â¯mg/kg b.wt orally), BCA (5â¯mg/kg b.wt intraperitoneally (I/P), co-treated group (BCAâ¯+â¯ANA), two control groups receiving even distilled water orally or DMSO I/P for twenty weeks. Bone turnover biomarkers BALP, OC, PTH, TRAP and TNFα were determined in serum. Bone mineral content, histological and morphometric measurements on rat femurs were performed. BMD by X-ray technique on tibias of rats and CT analysis of lumbar vertebrae of all treated and sham groups were applied. KEY FINDINGS: There was marked elevation in bone turnover biomarkers with high serum Ca and P content in the ANA-treated rats. Moreover marked elevation of TNFα, PTH, TC and TG, ANA caused severe changes in the BMD detected by X-ray in tibial bones and CT analysis of lumbar vertebrae of OVX rats. While I/P injection of BCA ameliorated the adverse bone health decrements caused by ANA. SIGNIFICANCE: The study highlights the importance of the BCA supplementation in accordance with the ANA therapy in case of ovariectomized rat model of osteoporosis which is clinically presented in Postmenopausal women with breast cancer during which considerable risk of developing osteoporosis is predicted during treatment.
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Adyuvantes Farmacéuticos/toxicidad , Anastrozol/toxicidad , Genisteína/farmacología , Osteoporosis/tratamiento farmacológico , Ovariectomía/efectos adversos , Fitoestrógenos/farmacología , Animales , Femenino , Osteoporosis/etiología , Ratas , Ratas Sprague-DawleyAsunto(s)
Carcinoma de Células de Merkel , Poliomavirus de Células de Merkel , Infecciones por Polyomavirus , Neoplasias Cutáneas , Infecciones Tumorales por Virus , Humanos , Carcinoma de Células de Merkel/patología , Infecciones Tumorales por Virus/patología , Neoplasias Cutáneas/patología , Infecciones por Polyomavirus/patologíaRESUMEN
Phthalates (such as DEHP) and bisphenol A (BPA) are widely used chemicals in plastics manufacturing and exert public health concerns as endocrine disrupters. This study was designed to investigate the deleterious effect of DEHP and BPA on endocrine profile of pregnant female rats and the combined treatment with ginseng extract (Panax ginseng). Seventy-two pregnant rats were divided into six groups (control, ginseng, DEHP, BPA, Gin + DEHP, and Gin + BPA), 12 females per each group. The drugs were supplemented from pregnancy day 0 until day 20. Determination of serum sex hormones (testosterone, progesterone, and estradiol) were determined on days 4, 10, and 20 of pregnancy. mRNA transcripts of STAR, HSD17B3, CYP17, AKT1, and PTEN were relatively quantified against ACTB in the ovary and placenta of days 10 and 20 pregnant females by relative quantitative polymerase-chain reaction (RQ-PCR). DEHP and BPA significantly decreased the endocrine profile of testosterone, progesterone, and estradiol of days 10 and 20 of pregnant females. Combined administration of these chemicals along with ginseng extracts has returned the hormones to normal levels when compared with the control group. The ovarian and placental CYP17 and HSD17B3 mRNA transcripts showed variable expression pattern in both tissues and they were significantly affected by DEHP and BPA administration, concomitantly correlating to STAR, AKT1, PTEN, progesterone, and testosterone levels on pregnancy days 10 and 20. The results confirm the reprotoxicity of DEHP and BPA as endocrine disruptors and indicate that ginseng could be used to alleviate the toxic effects of these chemicals.
Asunto(s)
Compuestos de Bencidrilo/toxicidad , Panax/química , Fenoles/toxicidad , Ácidos Ftálicos/toxicidad , Extractos Vegetales/administración & dosificación , Complicaciones del Embarazo/tratamiento farmacológico , Animales , Compuestos de Bencidrilo/análisis , Dietilhexil Ftalato/análisis , Dietilhexil Ftalato/toxicidad , Disruptores Endocrinos/análisis , Disruptores Endocrinos/toxicidad , Sistema Endocrino/efectos de los fármacos , Estradiol/sangre , Femenino , Humanos , Fenoles/análisis , Ácidos Ftálicos/análisis , Placenta/química , Placenta/efectos de los fármacos , Plásticos/análisis , Plásticos/toxicidad , Embarazo , Complicaciones del Embarazo/sangre , Complicaciones del Embarazo/inducido químicamente , Progesterona/sangre , Ratas , Testosterona/sangreRESUMEN
The toxicological studies on silver nanoparticles (Ag-NPs) have become a hot topic over the past few decades due to their unique properties on the nanoscale and widespread in many commercial products that launched into the market recently. This study was undertaken to shed light on Ag-NPs toxicity on neurotransmitters with special emphasis on the impact of concurrent administration of rutin with Ag-NPs in the experimental rats. The oral administration of Ag-NPs in rats induced brain oxidative stress, significant alterations in neurotransmitters and amino acids. Furthermore, transcriptional levels of glutamatergic N-methyl-d-aspartate (NMDA) receptors, monoamino oxidases (MAO-A, MAO-B) and metallothionein-III (MT-III) showed a significant elevation in Ag-NPs intoxicated rats. Moreover, histological examinations revealed astrogliosis and demyelination of neurons concomitant with neuronal degeneration and vacuolation. Strikingly, oral administration of rutin counterbalanced the toxic effects triggered by Ag-NPs. Taken together, our findings suggested that oral administration of Ag-NPs induced neurotoxicity in rats and rutin mitigates these effects.
Asunto(s)
Nanopartículas del Metal/efectos adversos , Neuronas/efectos de los fármacos , Síndromes de Neurotoxicidad/tratamiento farmacológico , Sustancias Protectoras/administración & dosificación , Rutina/administración & dosificación , Plata/efectos adversos , Aminoácidos/metabolismo , Animales , Masculino , Metalotioneína 3 , Monoaminooxidasa/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Neurotransmisores/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Receptores de N-Metil-D-Aspartato/metabolismo , Transcripción Genética/efectos de los fármacosRESUMEN
This study investigates the retrofitted role of thymoquinone (TQ) in the Th1/Th2 paradigm imbalance in lambda-cyhalothrin (LCT) treated rats. Four groups of male Wistar rats were formed: Group I served as control. Group II received 5 mg TQ/(kg bw) daily. Group III received 0.6 mg LCT/(kg bw). Group IV was treated with TQ and LCT. All treatments were given orally for 10 weeks. The LCT-treated group elicited a significant increase in MDA and NO levels with up-regulation of NF-κB/p65 and pro-inflammatory genes expression and their levels. Meanwhile, GSH and immunoglobulins concentrations were markedly decreased concomitant with lessening the activities of antioxidant enzymes and anti-inflammatory cytokine genes mRNA levels. The co-administration of TQ and LCT improved the altered antioxidant enzymes activities and concentration of cytokines with attenuation of NF-κB/p65 mRNA. These data support the antioxidant role of TQ in the Th1/Th2 imbalance paradigm during LCT toxicity.