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Potassium bromate (PB) is a general food additive, a significant by-product during water disinfection, and a carcinogen (Class II B). The compound emits toxicity depending on the extent of its exposure and dose through consumable items. The current study targeted disclosing the ameliorative efficacy of zinc oxide nanoparticles (ZnO NPs) prepared by green technology in PB-exposed Swiss albino rats. The rats were separated into six treatment groups: control without any treatment (Group I), PB alone (Group II), ZnO alone (Group III), ZnO NP alone (Group IV), PB + ZnO (Group V), and PB + ZnO NPs (Group VI). The blood and kidney samples were retrieved from the animals after following the treatment plan and kept at -20 °C until further analysis. Contrary to the control (Group I), PB-treated rats (Group II) exhibited a prominent trend in alteration in the established kidney function markers and disturbed redox status. Further, the analysis of the tissue and nuclear DNA also reinforced the biochemical results of the same treatment group. Hitherto, Groups III and IV also showed moderate toxic insults. However, Group VI showed a significant improvement from the PB-induced toxic insults compared to Group II. Hence, the present study revealed the significant therapeutic potential of the NPs against PB-induced nephrotoxicity in vivo, pleading for their usage in medicines having nephrotoxicity as a side effect or in enhancing the safety of the industrial use of PB.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Nanopartículas , Óxido de Zinc , Ratas , Animales , Óxido de Zinc/química , Bromatos/toxicidad , Estrés Oxidativo , Nanopartículas/química , Oxidación-Reducción , Potasio/farmacologíaRESUMEN
Biocompatible tryptophan-derived copper (1) and zinc (2) complexes with norharmane (ß-carboline) were designed, synthesized, characterized, and evaluated for the potential anticancer activity in vitro and in vivo. The in vitro cytotoxicity of both complexes 1 and 2 were assessed against two cancerous cells: (human breast cancer) MCF7 and (liver hepatocellular cancer) HepG2 cells with a non-tumorigenic: (human embryonic kidney) HEK293 cells. The results exhibited a potentially decent selectivity of 1 against MCF7 cells with an IC50 value of 7.8 ± 0.4 µM compared to 2 (less active, IC50 ~ 20 µM). Furthermore, we analyzed the level of glutathione, lipid peroxidation, and visualized ROS generation to get an insight into the mechanistic pathway and witnessed oxidative stress. These in vitro results were ascertained by in vivo experiments, which also supported the free radical-mediated oxidative stress. The comet assay confirmed the oxidative stress that leads to DNA damage. The histopathology of the liver also ascertained the low toxicity of 1.
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Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Carbolinas/farmacología , Cobre/farmacología , Triptófano/farmacología , Animales , Neoplasias de la Mama/metabolismo , Línea Celular , Línea Celular Tumoral , Ensayo Cometa/métodos , Daño del ADN/efectos de los fármacos , Femenino , Glutatión/metabolismo , Células HEK293 , Células Hep G2 , Humanos , Peroxidación de Lípido/efectos de los fármacos , Células MCF-7 , Estrés Oxidativo/efectos de los fármacos , Ratas , Especies Reactivas de Oxígeno/metabolismo , Zinc/farmacologíaRESUMEN
BACKGROUND: The liver disease is one of the most important traditional public health problems in Egypt. Oxidative stress is attributed to such pathological condition that further contributes to the initiation and progression of liver injury. In the present study, we have investigated if the strong antioxidant power of Nicotinamide (NA), Vitamin B2 (VB2), and Vitamin C (VC) can ameliorate TAA-induced oxidative stress-mediated liver injury in the rats. METHODS: Thirty-six albino rats were divided into six groups: Control group; TAA group (IP injection with TAA at a dosage of 200 mg/Kg three times a week for two months); TAA + NA group (rats administered with NA at a dosage of 200 mg/kg daily besides TAA as in the control); TAA + VB2 group (rats administered with vitamin B2 at a dosage of 30 mg/kg daily besides injection with TAA); TAA + VC group (rats administered with vitamin C at a dosage of 200 mg/kg daily along with injection of TAA). TAA + NA + VB + VC group (rats administered the with the three vitamins daily in TAA pre-injected at the respective doses described above). RESULTS: Treatment of rats with TAA led to a significant elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), total bilirubin, cholesterol, triglycerides, low-density lipoprotein (LDL) and tumor necrosis factor-alpha (TNF-α) in the serum samples. Moreover, malondialdehyde (MDA), hydroxyproline and nitic oxide (NO) were also significantly increased in the TAA-treated rats, while reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were significantly compromised in the hepatic samples. Rats administered with NA, VB2, and VC as individually or in combination ameliorated the deleterious effects of TAA that was confirmed by histopathology. However, the combination of the three vitamins was found more effective as compared to each of the vitamins. CONCLUSION: Our work demonstrates that NA, VB2, and VC cross-talk with each other that act as a more potent biochemical chain of antioxidant defense against TAA-induced toxicities in vivo.
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Ácido Ascórbico/administración & dosificación , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Niacinamida/administración & dosificación , Riboflavina/administración & dosificación , Animales , Antioxidantes/administración & dosificación , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Combinación de Medicamentos , Humanos , Hígado/efectos de los fármacos , Hígado/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Tioacetamida/toxicidadRESUMEN
BACKGROUND: Ant venom shows antimicrobial, anti-parasitic and anti-inflammatory activities, both in vitro and in vivo. Our recent studies have confirmed the role of samsum ant venom (SAV) as a powerful antioxidant. This study aimed to investigate whether SAV as a potential treatment for CCl4-induced acute liver toxicity in an animal (rat) model. METHODS: Thirty-two rats were assigned into four groups; the first one served as the control. The second group received a single dose of 1 ml/kg CCl4 in a 1:1 ratio with olive oil through an intraperitoneal injection. The third group received a single dose of 1 ml/kg CCl4 and then treated with SAV at a dose of 100 µg SAV twice a week for three weeks. The fourth group received a dose of 100 µg SAV only twice a week for three weeks. ELISA, RT-PCR and histopathological examinations were applied. RESULTS: Results showed that antioxidant enzymes were significantly reduced in the diseased animals. SAV was found to significantly restore the oxidative stability in diseased animals. ELISA estimation and RT-PCR analysis also showed significant upregulation of both nuclear factor (κB) NF-κB and inhibitor (κB) IκB, respectively, in the diseased animals compared to the normal ones. The expression of tumour necrosis factor alpha (TNF-α) and pro-apoptotic receptor (Fas) were also significantly up-regulated in the diseased rats. Interestingly, SAV was found to significantly restore NF-κB, IκB and TNF-α in the diseased rats to the normal values. As a result, liver enzymes, serum proteins and lipid concentrations were significantly improved by SAV in CCl4-animals in comparison with the control ones. Moreover, SAV obviously improved the hepatic tissues of the same group was. CONCLUSION: SAV treatment restores the normal biochemical and oxidative stability by improving the TNF-α/NF-κB mediated inflammation in CCL4-treated rats.
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Venenos de Hormiga/farmacología , Tetracloruro de Carbono/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Inflamación/metabolismo , Masculino , FN-kappa B/efectos de los fármacos , FN-kappa B/genética , Estrés Oxidativo/efectos de los fármacos , Sustancias Protectoras/farmacología , Ratas , Factor de Necrosis Tumoral alfa/efectos de los fármacos , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
BACKGROUND: Diabetes Mellitus (DM) is associated with pathological changes in the central nervous system (CNS) and alterations in oxidative stress. The aim of this study was to determine whether dietary supplement with whey protein (WP) could improve neurobehavior, oxidative stress and neuronal structure in the CNS. METHODS: Animals were distributed in three groups, a control group (N), a diabetic mellitus group (DM) and a DM group orally supplemented with WP (WP). RESULTS: The DM group of animals receiving WP had reduced blood glucose, significantly decreased free radical Diphenyl-picrylhydrazyl (DPPH) and lower lipid peroxidation in brain tissue. The WP group of animals showed improvement in balancing, coordination and fore-limb strength, oxidative stress and neuronal structure. CONCLUSION: The results of this study show that dietary supplementation with WP reduced oxidative stress, protected CNS neurons and improved the neurobehavior of diabetic mice.
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Conducta Animal/efectos de los fármacos , Química Encefálica/efectos de los fármacos , Diabetes Mellitus Experimental/psicología , Fármacos Neuroprotectores/farmacología , Proteína de Suero de Leche/farmacología , Animales , Compuestos de Bifenilo/metabolismo , Glucemia/metabolismo , Encéfalo/patología , Camelus , Diabetes Mellitus Experimental/patología , Fuerza de la Mano , Humanos , Peroxidación de Lípido/efectos de los fármacos , Ratones , Actividad Motora/efectos de los fármacos , Oxidación-Reducción , Picratos/metabolismoRESUMEN
BACKGROUND: Diabetes mellitus alters oxidative stability and immune response. Here, we investigated the impact of a peptide extracted from camel milk (CMP) on the oxidative status, transcription factor kappa-B (NF-kB) and inflammatory cytokine in diabetic wounds. METHODS: Rats were assigned into three groups: control, diabetic induced (DM) and diabetic induced with multiple doses of CMP for a week (DM-CMP). RESULTS: DM showed a sharp decline in the activity of major antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) compared to the control. The DM-CMP group, however, showed a noticeable replenishment in the activity of these enzymes compared to the DM group. The CMP-treated group also showed a normal level of lipid peroxidation marker (MDA) compared to the DM rats. Furthermore, ELISA analysis of serum TNF-α protein showed an elevated level in diabetic rats in comparison to control serum. However, RT-PCR analysis of locally wounded skin tissues revealed that diabetes down-regulates the RNA expression of both TNF-α and MIF genes in comparison to the control samples but that CMP was found to restore RNA expression significantly. Although it was elevated in CMP-treated rats after one day of wound incision, the NF-kB protein level was significantly decreased seven days after the incision in comparison to the animals in the diabetic group. CONCLUSION: CMP, therefore, can be seen an effective antioxidant and immune stimulant that induces oxidative stability and speeds up wound healing in diabetic model animals, making it a potential adjuvant in improving wound healing in those with diabetic conditions.
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Diabetes Mellitus Experimental/tratamiento farmacológico , Factores Inmunológicos/farmacología , Leche/química , Proteína de Suero de Leche/farmacología , Animales , Camelus , Colágeno/metabolismo , Dermis/metabolismo , Dermis/patología , Dermis/fisiopatología , Diabetes Mellitus Experimental/inmunología , Evaluación Preclínica de Medicamentos , Expresión Génica , Factores Inmunológicos/uso terapéutico , Masculino , FN-kappa B/metabolismo , Oxidación-Reducción , Estrés Oxidativo , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/genética , Proteína de Suero de Leche/uso terapéutico , Cicatrización de Heridas/efectos de los fármacosRESUMEN
BACKGROUND: Impaired wound healing is a complication of diabetes and a serious problem in clinical practice. We previously found that whey protein (WP) was able to regulate wound healing normally in streptozotocin (STZ)-diabetic models. This subsequent study was designed to assess the effect of WP on heat shock protein-72 (Hsp72) and keratin16 (Krt16) expression during wound healing in diabetic rats. METHODS: WP at a dosage of 100 mg/kg of body weight was orally administered daily to wounded normal and STZ-diabetic rats for 8 days. RESULTS: At day 4, the WP-treated diabetic wound was significantly reduced compared to that in the corresponding control. Diabetic wounded rats developed severe inflammatory infiltration and moderate capillary dilatation and regeneration. Treated rats had mild necrotic formation, moderate infiltration, moderate to severe capillary dilatation and regeneration, in addition to moderate epidermal formation. Hsp72 and Krt16 densities showed low and dense activity in diabetic wounded and diabetic wounded treated groups, respectively. At day 8, WP-treatment of diabetic wounded animals revealed great amelioration with complete recovery and closure of the wound. Reactivity of Hsp72 and Krt16 was reversed, showing dense and low, or medium and low, activity in the diabetic wounded and diabetic wounded treated groups, respectively. Hsp72 expression in the pancreas was found to show dense reactivity with WP-treated diabetic wound rats. CONCLUSION: This data provides evidence for the potential impact of WP in the up-regulation of Hsp72 and Krt16 in T1D, resulting in an improved wound healing process in diabetic models.
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Diabetes Mellitus Experimental/dietoterapia , Proteínas del Choque Térmico HSP72/metabolismo , Queratina-16/metabolismo , Proteína de Suero de Leche/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Proteínas del Choque Térmico HSP72/genética , Inmunohistoquímica , Queratina-16/genética , Dosificación Letal Mediana , Infiltración Neutrófila/efectos de los fármacos , Páncreas/metabolismo , Ratas , Piel/metabolismo , Regulación hacia ArribaRESUMEN
BACKGROUND: Interleukin-2 (IL-2) is a lymphocyte-activating and growth-promoting factor, and has been widely studied on T-cells and NK-cells. However, the interaction of polymorphonuclear neutrophils (PMNs) with IL-2 is poorly studied and thus, this study aimed at defining IL-2 participation in the expression of CD11b and CD18 on PMNs. MATERIAL AND METHODS: PMNs were isolated from heparinized whole blood of healthy donors. Purified cells were incubated with IL-2 (10 ng/ml) for 24 hours at 37°C in a humidified incubator with 5% CO2. After 24 hours' incubation, surface molecules (CD11b and CD18) were measured by flow cytometry. RESULTS: Interestingly, the antibodies of IL-2Rß chain (CD122-FITC) were found in all observed cells. The induction of CD11b mean fluorescence intensity (MFI) in highly purified PMNs stimulated with IL-2 was clearly increased recording 43% in comparison to the freshly isolated PMNs and the un-stimulated PMNs which were found to be 23% and 28% of CD11b, respectively. Furthermore, flow cytometry analysis demonstrated that the highly purified PMNs exposed to IL-2 showed an increase in CD18 MFI, recording 47% with respect to that of the freshly isolated PMNs and PMNs cultured with the medium alone which showed a small amount of 38% and 27%, respectively. CONCLUSIONS: Results demonstrated that CD11b and CD18 had been acquired on the surface of the IL-2-in vitro-activated PMNs. These findings indicated that IL-2 may play a crucial role in PMNs migration.
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The effects of Cadmium (Cd) exposure and the treatment with Zinc (Zn) on immune functions of splenocytes and cultured lymphocytes of rats were studied. The exposure of rats to Cd was at a dose of 2.2 mg/kg CdCl2, injected subcutaneously four times weekly for 2 months. Rats were supplemented with Zn (2.2 mg/kg ZnCl2, injected subcutaneously four times weekly for 2 months) one hour prior to Cd exposure. Spleens were removed and splenocytes were isolated and cultured. The proliferation capacity of lymphocytes and their homing to the spleen were studied. Ribonucleic acid (RNA) was extracted from stimulated lymphocytes in order to analyse gene expressions using RT-PCR. Accordingly, proliferation of lymphocytes was found to be suppressed in Cd-treated rats, both in vivo and in vitro. Zinc served to activate the proliferation of B and T lymphocytes in Cd-treated rats both in vivo and in vitro. Antigen-activated lymphocytes showed that Cd impaired the mRNA expression of CD68, Ccl22 and CXCL10. Zinc was not found to restore mRNA expression of these genes to the normal levels. Zinc was found to decrease the MDA level with replenishment of activity of key antioxidant enzymes and proteins in Cd-pre-treated animals significantly. Moreover, the histopathological examination of spleen samples also agreed with the molecular, immunological and redox findings. Hence, Zn is able to restore the normal structure, redox status and immunity in Cd-induced damage in the rat model system.
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This study aimed to explore the rate of decomposition of rabbit carcasses and the succession pattern of the associated dipteran flies outdoor, indoor, and on the roof of a 4-story building during the summer and winter. A total of 6,069 flies were recorded, with 30.91% reported as 2 waves outdoor and on the roof in the summer and 69.09% as 4 waves outdoor in the winter. The roof showed the most flies in the summer but the least in the winter, whereas the outdoor showed the most in the winter but the least in the summer. The ground and first floors showed the most indoor flies, while the second and third floors showed the least in both seasons. Indoor carcasses decomposed slower than those outdoor, and those on the second and third floors decomposed slower than those on the ground and first floors. Ten fly species from 8 families were identified in the winter, compared to 6 from 5 families in the summer. The most abundant species was Musca domestica Linnaeus (Muscidae) on the roof in the summer, while it was Chrysomya albiceps (Wiedemannn) (Calliphoridae) outdoor in the winter. The rare species (singletons) were Musca sp. (Muscidae) and Megaselia scalaris (Loew) (Phoridae) on the first floor in both seasons, Scaptomyza pallida (Zetterstedt) (Drosophilidae) on the ground floor in the summer, and Atherigona orientalis Schiner (Muscidae) outdoor in the winter. These data highlight the variance in carcass decomposition and fly composition across outdoor, indoor, and the roof of human dwellings, which could be of forensic importance.
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Dípteros , Entomología Forense , Estaciones del Año , Animales , Dípteros/fisiología , Conejos , Calliphoridae/crecimiento & desarrollo , Cambios Post Mortem , CadáverRESUMEN
BACKGROUND: Impaired diabetic wound healing occurs as a consequence of excessive reactive oxygen species (ROS) and inflammatory cytokine production. We previously found that whey protein (WP) was able to normally regulate the ROS and inflammatory cytokines during the inflammatory phase (first day) in streptozotocin (STZ)-diabetic wound healing. This study was designed to assess the effect of WP on metabolic status, the inflammation and anti-inflammation response, oxidative stress and the antioxidant defense system during different phases of the wound healing process in diabetic rats. WP at a dosage of 100 mg/kg of body weight, dissolved in 1% CMC, was orally administered daily to wounded normal (non-diabetic) and STZ-induced diabetic rats for 8 days starting from the 1st day after wounding. RESULTS: The data revealed that WP enhanced wound closure and was associated with an increase in serum insulin levels in diabetic rats and an alleviation of hyperglycemic and hyperlipidemic states in diabetic animals. The increase in insulin levels as a result of WP administration is associated with a marked multiplication of ß-cells in the core of islets of Langerhans. WP induced a reduction in serum TNF-α, IL-1ß and IL-6 levels and an increase in IL-10 levels, especially on the 4th day after wounding and treatment. WP also suppressed hepatic lipid peroxidation and stimulated the antioxidant defense system by increasing the level of glutathione and the activity of glutathione-S-transferase, glutathione peroxidase and superoxide dismutase (SOD) in wounded diabetic rats. CONCLUSIONS: WP was observed to enhance wound closure by improving the diabetic condition, limiting prolonged inflammation, suppressing oxidative stress and elevating the antioxidant defense system in diabetic rats.
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Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/patología , Inflamación/complicaciones , Inflamación/patología , Proteínas de la Leche/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Antioxidantes/metabolismo , Glucemia/metabolismo , Camelus , Proliferación Celular/efectos de los fármacos , Citocinas/metabolismo , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Insulina/sangre , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/metabolismo , Lípidos/sangre , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Proteínas de la Leche/administración & dosificación , Proteínas de la Leche/uso terapéutico , Oxidación-Reducción/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Desnaturalización Proteica , Ratas , Proteína de Suero de LecheRESUMEN
Hepatotoxicity is one of the significant side effects of chronic diabetes mellitus (DM) besides nephrotoxicity and pancreatitis. The management of this disease is much dependent on the restoration of the liver to its maximum functionality, as it is the central metabolic organ that gets severely affected during chronic diabetes. The present study investigates if the silver nanoparticles decorated with curcumin (AgNP-Cur) can enhance the efficacy of metformin (a conventional antidiabetic drug) by countering the drug-induced hepatoxicity. Swiss albino rats were categorized into six treatment groups (n = 6): control (group I without any treatment), the remaining five groups (group II, IV, V, VI) were DM-induced by streptozocin. Group II was untreated diabetic positive control, whereas groups III was administered with AgNP-cur (5 mg/kg). Diabetic group IV treated with metformin while V and VI were treated with metformin in a combination of the two doses of NPs (5 and 10 mg/kg) according to the treatment schedule. Biochemical and histological analysis of blood and liver samples were conducted after the treatment. The groups V and VI treated with the combination exhibited remarkable improvement in fasting glucose, lipid profile (HDL and cholesterol), liver function tests (AST, ALT), toxicity markers (GGT, GST and LDH), and redox markers (GSH, MDA and CAT) in comparison to group II in most of the parameters. Histological evaluation and comet assay further consolidate these biochemical results, pleading the restoration of the cellular structure of the target tissues and their nuclear DNA. Therefore, the present study shows that the NPs can enhance the anti-diabetic action by suppression of the drug-mediated hepatoxicity via relieving from oxidative stress, toxic burden and inflammation.
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The genus Capripoxvirus belongs to the Poxviridae family. The sheeppox, goatpox, and lumpy skin disease viruses are three species of this genus with 96% identity in their genomes. These are financially devastating viral infections among cattle, which cause a reduction in animal products and lead to a loss in livestock industries. In the current study, the phylogenetic analysis was carried out to reveal the evolutionary relationships of Capripoxvirus species (i.e., sheeppox virus (SPPV), goatpox virus (GTPV), and lumpy skin disease virus (LSDV)) with other viruses from the Poxviridae family with >96% query coverage to find the similarity index among all members. The three viruses (i.e., SPPV, GTPV, and LSDV) joined the clade of Capripoxvirus of the Poxviridae family in the phylogenetic tree and exhibited close evolutionary relationships. The multiple sequence alignment using ClustalOmega revealed significant variations in the protein sequences of the DNA-dependent RNA polymerase of SPPV, GTPV, and LSDV. The three-dimensional structures of five selected bee peptides and DNA-directed RNA polymerase of SPPV, GTPV, and LSDV were predicted using trRosetta and I-TASSER and used for molecular docking and simulation studies. The protein-protein docking was carried out using HADDOCK server to explore the antiviral activity of peptides as honey bee proteins against SPPV, GTPV, and LSDV. In total, five peptides were docked to DNA-directed RNA polymerase of these viruses. The peptides mellitin and secapin-1 displayed the lowest binding scores (-106.9 +/- 7.2 kcal/mol and -101.4 +/- 11.3 kcal/mol, respectively) and the best patterns with stable complexes. The molecular dynamics simulation indicated that the complex of protein DNA-dependent RNA polymerase and the peptide melittin stayed firmly connected and the peptide binding to the receptor protein was stable. The findings of this study provide the evidence of bee peptides as potent antimicrobial agents against sheeppox, goatpox, and lumpy skin disease viruses with no complexity.
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The efficacy of anticancer drug 5-FU is suppressed due to various factors, including severe side effects and decreased insensitivity during prolonged chemotherapy. Elevated endogenous copper (Cu) levels are one of the prominent hallmark features of cancer cells. In the present investigation, this feature was targeted in diethyl nitrosamine-phenobarbital-induced hepatocellular carcinoma (HCC) in a rat model system by an established anticancer drug, 5-FU, co-administered with copper and its chelating agent, disulfiram. After treatment with the test chemicals in HCC-induced rats, blood and liver samples were subjected to biochemical, molecular, and histopathological analyses. The analysis revealed that reactive oxygen species-mediated oxidative stress is the crucial etiological reason for the pathogenesis of HCC in rats, as evidenced by the significantly compromised activity of major antioxidant enzymes and elevated levels of oxidative damaged products with major histological alterations compared to the control. However, the combination of 5-FU with DSF demonstrated a significant improvement in most of the parameters, followed by 5-FU-Cu in the combination-treated groups. The combination treatment improved the histological details and triggered apoptosis in the cancer cells to a remarkable extent, as the levels of cleaved PARP and caspase-3 were significantly higher than those in the HCC rats treated with the drug alone. The present study envisages that manipulating the Cu-level greatly enhances the antineoplastic activity of 5-FU and sensitizes cancer cells to the increased efficacy of the drug.
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Hepatocellular carcinoma (HCC) is the second-largest cause of death among all cancer types. Many drugs have been used to treat the disease for a long time but have been mostly discontinued because of their side effects or the development of resistance in the patients with HCC. The administration of DZ orally is a great focus to address the clinical crisis. Daidzein (DZ) is a prominent isoflavone polyphenolic chemical found in soybeans and other leguminous plants. It has various pharmacological effects, including anti-inflammatory, antihemolytic, and antioxidant. This present study investigates the protective effect of DZ on chemically induced HCC in rat models. The DZ was administered orally four weeks before HCC induction and continued during treatment. Our study included four treatment groups: control (group 1, without any treatment), HCC-induced rats (group II), an HCC group treated with DZ at 20 mg/kg (group III), and an HCC group treated with DZ at 40 mg/kg (group IV). HCC rats showed elevation in all the HCC markers (AFP, GPC3, and VEGF), liver function markers (ALP, ALT, and AST), inflammatory markers (IL-6, TNF-α, and CRP), and lipid markers concomitant with a decrease in antioxidant enzymes and protein. However, groups III and IV demonstrated dose-dependent alleviation in the previous parameters resulting from HCC. In addition, the high dose of DZ reduces many hepatological changes in HCC rats. All study parameters improved with DZ administration. Due to its antioxidant and anti-inflammatory characteristics, DZ is a promising HCC treatment option for clinical use.
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This study was designed to evaluate the trace elements (minerals) in forages fed to sheep and their effect on gastrointestinal parasite burdens. The ultimate objective was to determine the correlation between the burden of gastrointestinal (GI) parasites and the level of trace minerals in sheep serum as a result of the forages they grazed on. A total of 384 faecal samples were collected from sheep in each of the districts (Sialkot and Multan) and examined quantitatively using the McMaster technique. Serum collected from them and plants were pre-treated, and spectrophotometry was used to determine the concentration of trace minerals (Mn, Co, Cu, and Zn). The level of these trace elements differed significantly (P < 0.05) in forages from both districts. In the district of Sialkot, the highest concentrations (mg/Kg) of Zn (38.53 ± 0.16) were found in Cichorium intybus, Cu (41.57 ± 0.07) in Cynodon dactylon, Mn (39.61 ± 0.05) in Parthenium hysterophorus, and Co (1.42 ± 0.03) in Coronopus didymus. In the district of Multan, the highest concentrations (mg/Kg) of Zn (39.43 ± 0.46) were found in Cichorium intybus, Cu (25.76 ± 0.36) in Cynodon dactylon, Mn (34.29 ± 0.53) in Launaea nudicaulis, and Co (1.74 ± 0.08) in Brachiaria raptens. The prevalence of GI parasites in sheep populations in district Sialkot was 34%, while in district Multan, it was 32%. In tehsil Sialkot of district Sialkot, Zn and Cu were significantly (P < 0.05) correlated with eggs per gram (EPG) of faeces, while in tehsil Multan City of district Multan, only Cu was significantly (P < 0.05) correlated with EPG. The potential mechanism behind the role of trace minerals in lowering the burdens of GI parasites requires more investigation. It is recommended that plants with high content of trace minerals should be utilized as part of comprehensive preventive and control strategies against GI parasitism in ruminant animals like sheep.
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BACKGROUND: Studies have demonstrated that vitamin C supplementation enhances the immune system, prevents DNA damage, and decreases the risk of a wide range of diseases. Other study reported that leukocyte vitamin C level was low in diabetic individuals compared with nondiabetic controls. AIM OF THE WORK: To study the effect of vitamin C on oxidative stress, blood lipid profile, and T-cell responsiveness during streptozotocin (STZ)-induced type I diabetes mellitus. METHODS: Thirty male Sprague-Dawley rats were randomly split into three groups. The first served as a control group (n = 10) in which rats were injected with the vehicle alone. The second (n = 10) and the third groups (n = 10) were rendered diabetic by intraperitoneal (i.p.) injection of single doses of STZ (60 mg/kg body weight). The third group was supplemented with vitamin C (100 mg/kg body weight) for 2 months. RESULTS: T lymphocytes from the diabetic rats were found to be in a stunned state, with a decreased surface expression of the CD28 costimulatory molecule, low levels of phosphorylated AKT, altered actin polymerization, diminished proliferation and cytokine production, and, eventually, a marked decrease in abundance in the periphery. Vitamin C was found to significantly decrease the elevated levels of blood hydroperoxide, glucose, cholesterol, triglycerides and low-density lipoprotein (LDL) in diabetic rats. Furthermore, it was found to restore CD28 expression, AKT phosphorylation, actin polymerization, and polyfunctional T cells (IFN-γ- and IL-2-producing cells that exhibit a high proliferation capacity). CONCLUSION: Vitamin C treatment restores and reconstitutes polyfunctional, long-lived T cells in diabetic rats.
Asunto(s)
Ácido Ascórbico/administración & dosificación , Diabetes Mellitus Experimental/tratamiento farmacológico , Suplementos Dietéticos , Linfocitos T/efectos de los fármacos , Vitaminas/administración & dosificación , Animales , Antioxidantes , Western Blotting , Antígenos CD28/genética , Antígenos CD28/metabolismo , Proliferación Celular/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Diabetes Mellitus Experimental/fisiopatología , Regulación hacia Abajo , Sistema Inmunológico/efectos de los fármacos , Interferón gamma/metabolismo , Interleucina-2/metabolismo , Lipoproteínas LDL/sangre , Masculino , Estrés Oxidativo/efectos de los fármacos , Fosforilación , Ratas , Ratas Sprague-Dawley , Factores de Riesgo , Transducción de Señal , Estreptozocina/efectos adversos , Linfocitos T/metabolismo , Triglicéridos/sangreRESUMEN
BACKGROUND: This study aimed at investigating the oxidative stress ameliorating effect, lipids profile restoration, and the anti-inflammatory effect of Samsum Ant Venom (SAV) in induced endotoxemic male rats, injected with bacterial lipopolysaccharides (LPS). RESULTS: Results revealed that LPS significantly increased the oxidative stress indications in LPS-injected rats. A significant increase of both malondialdehyde (MDA), and advanced oxidative protein products (AOPP), as well as a significant suppression of glutathione were all detected. Treatment with 100 µg/kg dose of SAV significantly restored the oxidative stress normal indications and increased the total glutathione levels. Treatment of the LPS-rats with 100 µg/kg dose of SAV showed a clear anti-inflammatory function; as the histological architecture of the hepatic tissue was partially recovered, along with a valuable decrease in the leukocytes infiltrated the hepatic tissues. Treatment of some rat groups with 600 µg/kg dose of SAV after LPS injection induced a severe endotoxemia that resulted in very high mortality rates. SAV versus the effects of LPS on AKT1, Fas, TNF-α and IFN-γ mRNA expression. SAV was found to significantly lower Fas gene expression comparing to the LPS group and restore the level of IFN-γ mRNA expression to that of the control group. CONCLUSION: In conclusion, SAV, at the dose of 100 µg/kg body weight, maintained and restored the oxidative stability, the anti-inflammatory, and the hypolipidemic bioactivity in rats after induced disruption of these parameters by LPS injection. This improvement by SAV was mediated by upregulation of AKT1.
Asunto(s)
Antiinflamatorios/uso terapéutico , Antioxidantes/metabolismo , Hormigas/química , Lipopolisacáridos/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ponzoñas/uso terapéutico , Animales , Endotoxemia/inducido químicamente , Endotoxemia/tratamiento farmacológico , Glutatión/metabolismo , Interferón gamma/metabolismo , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The bioactivity of nanoparticles has engendered a promise in scientific communities for developing novel therapeutic strategies. This study investigated the protective effects of selenium nanoparticles (SeNPs) against kidney injury in streptozocin-induced diabetes during pregnant (DDP) rats. The female rats were separated into three groups (n = 8). Group 1 received the vehicle, normal saline. Group 2 received a single intraperitoneal dose of 50 mg/kg of streptozocin. Group 3 received a single intraperitoneal injection of 50 mg/kg of streptozocin, followed by treatment with SeNPs at a dose of 2.5 mg/kg twice a week for 6 weeks (1 week before gestation and continuing for 5 additional weeks). The structure formed by the fabricated SeNPs with citric acid in the presence of ascorbic acid indicated that nano-Se was associated with a carbon matrix. The diabetic group suffered from polyuria, a reduction in body weight, delayed gestation, and only 40% successful pregnancy compared with the control rats. Interestingly, SeNPs significantly reduced the rate of urination, accelerated the start of gestation, and increased the percentage of successful pregnancy in females with DM. Severe changes were observed in the pancreatic ß-cells of the diabetic rats, with darkly stained and fragmented chromatin in nuclei, while SeNPs partially restored the normal morphological features of the pancreatic ß-cells. The concentrations of urea, creatinine, MDA, and glucose were significantly increased in the diabetic rats, while GSH was significantly reduced compared with controls. Interestingly, SeNPs restored all of these parameters to values at or near control levels. SeNPs were capable of improving the histological structure of the kidney in mothers with DDP. Hence, the present work is relevant to GDM demonstrating SeNPs shielding the kidney structure and function in vivo.