RESUMO
This study investigated the stimulatory effects of dietary inclusion of Gracilariopsis persica (GP), Hypnea flagelliformis (HF) and Sargassum boveanum (SB) on immune indices, antioxidant capability and immune related genes expression of rainbow trout (Oncorhynchus mykiss). Seven iso-nitrogenous and iso-caloric diets with 0, 5 and 10% of each macroalgae were prepared and fed to rainbow trout juveniles for 83 days. Serum lysozyme (Lyz) and respiratory burst activity (NBT) along with activity of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) and expression of LyzII, TNFα and IL-1ß genes in head kidney samples were determined by days 47 and 83. Our results revealed that dietary inclusion of seaweeds improved fish immune status. Long term feeding of fish on seaweed contained diets (except for GP10) improved serum Lyz activity in comparison to control group. Similarly, extended feeding on GP5 and HF10 and HF10 included diets improved SOD and POD levels, respectively. Genes expression studies revealed that seaweeds contained diets noticeably enhanced expression of LyzII, TNFα and IL-1ß in comparison to control fish. However, results revealed that such stimulatory effects were more evident at lower dietary inclusion level and shorter feeding time. In conclusion, the results depicted that dietary inclusion of the seaweeds effectively improved serum immune indices and head kidney antioxidant status and immune related genes expression in a time and dose dependent manner.
Assuntos
Oncorhynchus mykiss/imunologia , Rodófitas , Sargassum , Alga Marinha , Animais , Catalase/imunologia , Dieta/veterinária , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Rim Cefálico/imunologia , Imunomodulação , Interleucina-1beta/genética , Muramidase/sangue , Muramidase/genética , Oncorhynchus mykiss/genética , Oxirredutases/imunologia , Superóxido Dismutase/imunologia , Fator de Necrose Tumoral alfa/genética , Regulação para CimaRESUMO
A 56-day research was performed to examine the influence of graded levels (0 (control), 0.5, 1 and 2%) of Fern (Adiantum capillus-veneris) leaves powder (FLP) in diet on immune competence and growth of common carp (Cyprinus carpio, initial weight = 20 g). The serum total immunoglobulins content and lysozyme activity in the 1 and 2% FLP groups remarkably increased compared to the other groups (P < 0.05). The skin mucosal lysozyme activity enhanced with increasing dietary FLP level in a dose-response manner. Fish fed on the FLP-supplemented diets had higher skin-mucosal superoxide dismutase activity than the control (P < 0.05). However, serum antioxidant enzymes were not affected by dietary fern (P > 0.05). The serum bactericidal activity against human and fish pathogens increased with enhancing the FLP level in diet against Staphylococcus aureus, Escherichia coli (EHEC ATCC 43895), Escherichia coli (CI), Pseudomonas aeruginosa, Klebsiella pneumonia and Aeromonas hydrophila. The serum antibacterial activity against Yersinia ruckeri in the 2% FLP group was higher than the other treatments. Furthermore, the serum bactericidal activity against P. aeruginosa (ATCC 27853) only observed in fish fed on the 1 and 2% FLP-supplemented diets. The skin mucosal bactericidal activity and inhibitory effects increased with enhancing the FLP level in diet against E. coli, K. pneumonia, Y. ruckeri and A. hydrophila in a dose response manner. Moreover, the skin mucosal bactericidal activity against S. aureus only observed in fish fed on 1 and 2% FLP-supplemented diets. The weight gain values in the 1 and 2% FLP groups were higher than the other treatments (P < 0.05). Feed conversion ratio (FCR) improved with increasing FLP level in diet in a dose-response manner (P < 0.05). By considering serum and mucosal bactericidal activities against different pathogenic bacteria, the supplementation of 2% FLP in diet is recommended for C. carpio during grow-out phase.
Assuntos
Adiantum , Bactérias/crescimento & desenvolvimento , Carpas/imunologia , Muco/imunologia , Muramidase/imunologia , Preparações de Plantas/farmacologia , Soro , Pele/imunologia , Animais , Carpas/sangue , Carpas/crescimento & desenvolvimento , Catalase/imunologia , Dieta/veterinária , Imunoglobulinas/sangue , Muco/enzimologia , Muramidase/sangue , Folhas de Planta , Pós , Superóxido Dismutase/imunologiaRESUMO
The effect of diet enriched with dried lemon (Citrus limon) peel was fed to Labeo rohita at three different levels (0, 1, 2.5, and 5 g kg-1) for a period of 60 days; the impact of the diet on the hematology, antioxidant activity and immunological reaction and gene expression against Aeromonas sorbia is reported. In both un-challenged and challenged groups treated with 2.5 g and 5 g kg-1 dried lemon peel diets, the enhanced significant changes are: the weight gain and specific growth rate, white blood cell and total protein content, the antioxidants: superoxide dismutase, catalase, glutathione peroxidase, and glutathione activities, the respiratory burst, alternative complement pathway, complement C3, and total immunoglobulin M levels. Similarly, the heat shock protein-70 and -90, superoxide dismutase, glutathione peroxidase, glutathione, interleukin-1ß and -8, tumor necrosis factor alpha, inducible nitric oxide synthase, transforming growth factor beta, and immunoglobulin M were up-regulated significantly. Any dried lemon peel enriched diet increased the phagocytic and lysozyme activities significantly in both groups. In the un-challenged group treated with 0 g kg-1 diet or in both groups treated with 2.5 g kg-1 diet the SR was 100%. These results indicate that in both un-challenged and challenged-treated groups the 2.5 and 5 g kg-1 dried lemon peel enriched diets positively modulate growth rate, physiology, and antioxidant status, innate-adaptive immune response as well as antioxidant and immune related gene expression in L. rohita against A. sorbia.
Assuntos
Aeromonas , Antioxidantes/farmacologia , Citrus , Cyprinidae , Doenças dos Peixes/imunologia , Frutas , Infecções por Bactérias Gram-Negativas/imunologia , Animais , Catalase/genética , Catalase/imunologia , Complemento C3/imunologia , Cyprinidae/genética , Cyprinidae/crescimento & desenvolvimento , Cyprinidae/imunologia , Citocinas/genética , Dieta/veterinária , Doenças dos Peixes/genética , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Glutationa/imunologia , Glutationa Peroxidase/genética , Glutationa Peroxidase/imunologia , Infecções por Bactérias Gram-Negativas/genética , Infecções por Bactérias Gram-Negativas/veterinária , Rim Cefálico/imunologia , Imunoglobulina M/imunologia , Muramidase/imunologia , Superóxido Dismutase/genética , Superóxido Dismutase/imunologiaRESUMO
In the current study, we investigated the effect of a probiotic bacterium (Lactobacillus rhamnosus ATCC 7469) microencapsulated with alginate and hi-maize starch and coated with chitosan on improving growth factors, body composition, blood chemistry, and the immune response of rainbow trout (initial weight: 18.41 ± 0.32 g). Four experimental diets were formulated to feed fish for 60 days. They were control diet without any additive (C), diet added with beads without probiotic (E), a probiotic sprayed to the diet (L.r), and encapsulated probiotic supplemented diet (E-L.r). The results indicated that feeding with E-Lr significantly improved weight gain (84.98 g) and feed conversion ratio (0.95) compared to the other groups (P < 0.05). Also, fish fed E-Lr diet had a significantly higher value of whole-body protein (17.51%), total protein in the blood (4.98 g/dL), lysozyme (30.66 U/mL), alternative complement pathway hemolytic activity (134 U/mL), superoxide dismutase (203 U/mg protein), and catalase (528.33 U/mg protein) (P < 0.05) as compared to those fed the control diet. Similarly, a higher relative expression of immune-related genes such as interleukin-1 (Il-1) and tumor necrosis factor-alpha (TNF-1α) were reported in those fed E-L.r and L.r diets respectively. Interestingly, the fish fed dietary E-L.r had a significantly lower value of lipid in the whole body (4.82%) and cholesterol in the blood (160.67%) in comparison with those fed the control diet (P < 0.05). At the end of the experiment, all groups were challenged by Yersinia ruckeri where the survival rate of rainbow trout fed dietary E-L.r (70.36%) was statistically higher than that of the others (P < 0.05). Overall, the results suggested that encapsulated probiotic Lact. rhamnosus ATCC 7469 acted better than unencapsulated probiotic and has a potential to improve growth performance, flesh quality, and the immune response of rainbow trout.
Assuntos
Doenças dos Peixes/terapia , Proteínas de Peixes/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Lacticaseibacillus rhamnosus/fisiologia , Oncorhynchus mykiss/imunologia , Probióticos/farmacologia , Yersiniose/terapia , Alginatos/química , Ração Animal/análise , Animais , Composição Corporal/efeitos dos fármacos , Catalase/genética , Catalase/imunologia , Encapsulamento de Células/métodos , Células Imobilizadas , Quitosana/química , Colesterol/sangue , Via Alternativa do Complemento/efeitos dos fármacos , Dieta , Resistência à Doença/efeitos dos fármacos , Resistência à Doença/genética , Resistência à Doença/imunologia , Doenças dos Peixes/imunologia , Doenças dos Peixes/microbiologia , Proteínas de Peixes/imunologia , Regulação da Expressão Gênica/imunologia , Interleucina-1/genética , Interleucina-1/imunologia , Muramidase/genética , Muramidase/imunologia , Oncorhynchus mykiss/crescimento & desenvolvimento , Oncorhynchus mykiss/microbiologia , Superóxido Dismutase/genética , Superóxido Dismutase/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Aumento de Peso/efeitos dos fármacos , Yersiniose/imunologia , Yersiniose/microbiologia , Yersinia ruckeri/efeitos dos fármacos , Yersinia ruckeri/crescimento & desenvolvimento , Yersinia ruckeri/patogenicidadeRESUMO
BACKGROUND: Immune checkpoint blockades (ICBs) are a promising treatment for cancers such as melanoma by blocking important inhibitory pathways that enable tumor cells to evade immune attack. Programmed death ligand 1 monoclonal antibodies (aPDL1s) can be used as an ICB to significantly enhance the effectiveness of tumor immunotherapy by blocking the PD-1/PD-L1 inhibitory pathway. However, the effectiveness of aPDL1s may be limited by low selectivity in vivo and immunosuppressed tumor microenvironment including hypoxia. PURPOSE: To overcome the limitations, we develop a multifunctional immunoliposome, called CAT@aPDL1-SSL, with catalase (CAT) encapsulated inside to overcome tumor hypoxia and aPDL1s modified on the surface to enhance immunotherapeutic effects against melanoma. METHODS: The multifunctional immunoliposomes (CAT@aPDL1-SSLs) are prepared using the film dispersion/post-insertion method. The efficacy of CAT@aPDL1-SSLs is verified by multiple experiments in vivo and in vitro. RESULTS: The results of this study suggest that the multifunctional immunoliposomes preserve and protect the enzyme activity of CAT and ameliorate tumor hypoxia. Moreover, the enhanced cellular uptake of CAT@aPDL1-SSLs in vitro and their in vivo biodistribution suggest that CAT@aPDL1-SSLs have great targeting ability,resulting in improved delivery and accumulation of immunoliposomes in tumor tissue.Finally, by activating and increasing the infiltration of CD8+ T cells at the tumor site, CAT@aPDL1-SSLs inhibit the growth of tumor and prolong survival time of mice,with low systemic toxicity. CONCLUSION: In conclusion, the multifunctional immunoliposomes developed and proposed in this study are a promising candidate for melanoma immunotherapy, and could potentially be combined with other cancer therapies like radiotherapy and chemotherapy to produce positive outcomes.
Assuntos
Antineoplásicos Imunológicos/farmacologia , Antígeno B7-H1/imunologia , Catalase/imunologia , Lipossomos/química , Melanoma/tratamento farmacológico , Hipóxia Tumoral/efeitos dos fármacos , Animais , Anticorpos Monoclonais/farmacologia , Antineoplásicos Imunológicos/química , Antineoplásicos Imunológicos/farmacocinética , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Catalase/química , Linhagem Celular Tumoral , Feminino , Imunoterapia/métodos , Lipossomos/administração & dosagem , Lipossomos/farmacologia , Melanoma/patologia , Camundongos Endogâmicos C57BL , Fosfatidiletanolaminas/química , Polietilenoglicóis/química , Distribuição Tecidual , Microambiente Tumoral/efeitos dos fármacosRESUMO
Bacterial catalase is important for intracellular survival of the bacteria. This protein of Propionibacterium acnes, one of possible causes of sarcoidosis, induces hypersensitive Th1 immune responses in sarcoidosis patients. We examined catalase expression in cultured P. acnes isolated from 19 sarcoid and 18 control lymph nodes and immunohistochemical localization of the protein in lymph nodes from 43 sarcoidosis and 102 control patients using a novel P. acnes-specific antibody (PAC) that reacts with the catalase protein, together with the previously reported P. acnes-specific PAB and TIG antibodies. High catalase expression of P. acnes cells was found during stationary phase in more isolates from sarcoid than from non-sarcoid lymph nodes and was associated with bacterial survival under H2O2-induced oxidative stress. In many sarcoid and some control lymph nodes, catalase expression was detected at the outer margins of PAB-reactive Hamazaki-Wesenberg (HW) bodies in sinus macrophages, the same location as catalase expression on the surface of cultured P. acnes and the same distribution as bacterial cell membrane-bound lipoteichoic acid in HW bodies. Some or no catalase expression was detected in sarcoid granulomas with PAB reactivity or in clustered paracortical macrophages packed with many PAB-reactive small-round bodies. HW bodies expressing catalase may be persistent P. acnes in sinus macrophages whereas PAB-reactive small-round bodies with undetectable catalase may be activated P. acnes proliferating in paracortical macrophages. Intracellular proliferation of P. acnes in paracortical macrophages may lead to granuloma formation by this commensal bacterium in sarcoidosis patients with Th1 hypersensitivity to certain P. acnes antigens, including catalase.
Assuntos
Catalase/genética , Expressão Gênica , Linfonodos/imunologia , Linfonodos/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Propionibacterium acnes/genética , Propionibacterium acnes/imunologia , Adulto , Idoso , Anticorpos Antibacterianos/imunologia , Especificidade de Anticorpos , Bactérias , Biópsia , Catalase/imunologia , Catalase/metabolismo , Feminino , Imunofluorescência , Humanos , Imuno-Histoquímica , Linfonodos/microbiologia , Linfonodos/patologia , Macrófagos/microbiologia , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Propionibacterium acnes/enzimologia , Sarcoidose/etiologia , Sarcoidose/metabolismo , Sarcoidose/patologiaRESUMO
Organisms possess a cellular antioxidant defense system inclusive of ROS scavengers to maintain the homeostasis of antioxidant levels. Catalase is a major ROS scavenger enzyme that plays a significant role in the antioxidant defense mechanism of organisms by reducing toxic hydrogen peroxide molecules into a nontoxic form of oxygen and water with a high turnover rate. In the present study, we performed molecular and functional characterization of the catalase homolog from Hippocampus abdominalis (HaCat). The HaCat cDNA sequence was identified as a 1578 bp ORF (open reading frame) that encodes a polypeptide of 526 amino acids with 59.33â¯kDa molecular weight. Its estimated pI value is 7.7, and it does not have any signal sequences. HaCat shared a conserved domain arrangement including the catalase proximal active site signature and heme ligand signature domain with the previously identified catalase counterparts. Phylogenetic analysis displayed close evolutionary relationships between HaCat and catalases from other teleost fish. According to our qPCR results, ubiquitous expression of HaCat transcripts were observed in all the tested tissues with high expression in the kidney followed by liver. Significant modulations of HaCat transcription were observed in blood, liver, and kidney tissues post-challenge with Streptococcus iniae, Edwardsiella tarda, poly I:C, and LPS. Peroxidase activity of recombinant HaCat (rHaCat) was evaluated using an ABTS assay and the ROS removal effect was further confirmed by oxidative DNA damage protection and cell viability assays. The rHaCat showed more than 97% activity over a temperature and pH range of 10⯰C-40⯰C and 5 to 6, respectively. The above results suggest that HaCat plays an indispensable role in the oxidative homeostasis of the seahorse during pathogenic attack.
Assuntos
Catalase/genética , Catalase/imunologia , Doenças dos Peixes/imunologia , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Smegmamorpha/genética , Smegmamorpha/imunologia , Sequência de Aminoácidos , Animais , Catalase/química , Clonagem Molecular , Edwardsiella tarda/fisiologia , Infecções por Enterobacteriaceae/imunologia , Infecções por Enterobacteriaceae/veterinária , Proteínas de Peixes/química , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Perfilação da Expressão Gênica/veterinária , Lipopolissacarídeos/farmacologia , Filogenia , Poli I-C/farmacologia , Alinhamento de Sequência/veterinária , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/veterinária , Streptococcus iniae/fisiologiaRESUMO
The recent years have witnessed the blooming of cancer immunotherapy, as well as their combinational use together with other existing cancer treatment techniques including radiotherapy. However, hypoxia is one of several causes of the immunosuppressive tumor microenvironment (TME). Herein, we develop an innovative strategy to relieve tumor hypoxia by delivering exogenous H2O2 into tumors and the subsequent catalase-triggered H2O2 decomposition. In our experiment, H2O2 and catalase are separately loaded within stealthy liposomes. After intravenous (iv) preinjection of CAT@liposome, another dose of H2O2@liposome is injected 4 h later. The sustainably released H2O2 could be decomposed by CAT@liposome, resulting in a long lasting effect in tumor oxygenation enhancement. As the result, the combination treatment by CAT@liposome plus H2O2@liposome offers remarkably enhanced therapeutic effects in cancer radiotherapy as observed in a mouse tumor model as well as a more clinically relevant patient-derived xenograft tumor model. Moreover, the relieved tumor hypoxia would reverse the immunosuppressive TME to favor antitumor immunities, further enhancing the combined radio-immunotherapy with cytotoxic T lymphocyte-associated antigen 4 (CTLA4) blockade. This work presents a simple yet effective strategy to promote tumor oxygenation via sequential delivering catalase and exogenous H2O2 into tumors using well-established liposomal carriers, showing great potential for clinical translation in radio-immunotherapy of cancer.
Assuntos
Catalase/administração & dosagem , Peróxido de Hidrogênio/administração & dosagem , Neoplasias/imunologia , Neoplasias/radioterapia , Animais , Catalase/química , Catalase/imunologia , Linhagem Celular Tumoral , Terapia Combinada , Humanos , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/imunologia , Lipossomos/administração & dosagem , Lipossomos/imunologia , Camundongos , Neoplasias/patologia , Neoplasias/terapia , Oxigênio/química , Oxigênio/metabolismo , Radioimunoterapia , Hipóxia Tumoral/imunologia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologiaRESUMO
Exosomes are nanovesicles released from most cell types including immune cells. Prior studies suggest exosomes play a role in HIV pathogenesis, but little is known about exosome cargo in relation to immune responses and oxidative stress. Here, we characterize plasma exosomes in HIV patients and their relationship to immunological and oxidative stress markers. Plasma exosome fractions were isolated from HIV-positive subjects on ART with suppressed viral load and HIV-negative controls. Exosomes were characterized by electron microscopy, nanoparticle tracking, immunoblotting, and LC-MS/MS proteomics. Plasma exosomes were increased in HIV-positive subjects compared to controls, and correlated with increased oxidative stress markers (cystine, oxidized cys-gly) and decreased PUFA (DHA, EPA, DPA). Untargeted proteomics detected markers of exosomes (CD9, CD63, CD81), immune activation (CD14, CRP, HLA-A, HLA-B), oxidative stress (CAT, PRDX1, PRDX2, TXN), and Notch4 in plasma exosomes. Exosomal Notch4 was increased in HIV-positive subjects versus controls and correlated with immune activation markers. Treatment of THP-1 monocytic cells with patient-derived exosomes induced expression of genes related to interferon responses and immune activation. These results suggest that exosomes in ART-treated HIV patients carry proteins related to immune activation and oxidative stress, have immunomodulatory effects on myeloid cells, and may have pro-inflammatory and redox effects during pathogenesis.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Exossomos/imunologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Metaboloma/imunologia , Proteoma/imunologia , Antígenos CD/genética , Antígenos CD/imunologia , Terapia Antirretroviral de Alta Atividade , Biomarcadores/metabolismo , Estudos de Casos e Controles , Catalase/genética , Catalase/imunologia , Cromatografia Líquida de Alta Pressão , Biologia Computacional/métodos , Cistina/imunologia , Cistina/metabolismo , Exossomos/genética , Exossomos/metabolismo , Ácidos Graxos Insaturados/imunologia , Ácidos Graxos Insaturados/metabolismo , HIV/efeitos dos fármacos , HIV/imunologia , HIV/patogenicidade , Infecções por HIV/genética , Infecções por HIV/virologia , Antígenos HLA/genética , Antígenos HLA/imunologia , Humanos , Imunidade Inata , Fatores Reguladores de Interferon/genética , Fatores Reguladores de Interferon/imunologia , Metaboloma/genética , Estresse Oxidativo , Peroxirredoxinas/genética , Peroxirredoxinas/imunologia , Proteoma/genética , Receptor Notch4/genética , Receptor Notch4/imunologia , Células THP-1 , Espectrometria de Massas em TandemRESUMO
Downy mildew of pearl millet caused by the biotrophic oomycete Sclerospora graminicola is the most devastating disease which impairs pearl millet production causing huge yield and monetary losses. Chitosan nanoparticles (CNP) were synthesized from low molecular weight chitosan having higher degree of acetylation was evaluated for their efficacy against downy mildew disease of pearl millet caused by Sclerospora graminicola. Laboratory studies showed that CNP seed treatment significantly enhanced pearl millet seed germination percentage and seedling vigor compared to the control. Seed treatment with CNP induced systemic and durable resistance and showed significant downy mildew protection under greenhouse conditions in comparison to the untreated control. Seed treatment with CNP showed changes in gene expression profiles wherein expression of genes of phenylalanine ammonia lyase, peroxidase, polyphenoloxidase, catalase and superoxide dismutase were highly upregulated. CNP treatment resulted in earlier and higher expression of the pathogenesis related proteins PR1 and PR5. Downy mildew protective effect offered by CNP was found to be modulated by nitric oxide and treatment with CNP along with NO inhibitors cPTIO completely abolished the gene expression of defense enzymes and PR proteins. Further, comparative analysis of CNP with Chitosan revealed that the very small dosage of CNP performed at par with recommended dose of Chitosan for downy mildew management.
Assuntos
Quitosana/farmacologia , Resistência à Doença/genética , Nanopartículas/química , Óxido Nítrico/biossíntese , Pennisetum/efeitos dos fármacos , Proteínas de Plantas/genética , Acetilação , Benzoatos/farmacologia , Catalase/antagonistas & inibidores , Catalase/genética , Catalase/imunologia , Catecol Oxidase/antagonistas & inibidores , Catecol Oxidase/genética , Catecol Oxidase/imunologia , Quitosana/química , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/imunologia , Germinação/fisiologia , Imidazóis/farmacologia , Óxido Nítrico/agonistas , Óxido Nítrico/antagonistas & inibidores , Pennisetum/genética , Pennisetum/imunologia , Pennisetum/microbiologia , Peronospora/crescimento & desenvolvimento , Peronospora/patogenicidade , Peroxidase/antagonistas & inibidores , Peroxidase/genética , Peroxidase/imunologia , Fenilalanina Amônia-Liase/antagonistas & inibidores , Fenilalanina Amônia-Liase/genética , Fenilalanina Amônia-Liase/imunologia , Doenças das Plantas/genética , Doenças das Plantas/imunologia , Doenças das Plantas/microbiologia , Proteínas de Plantas/antagonistas & inibidores , Proteínas de Plantas/imunologia , Plântula/efeitos dos fármacos , Plântula/genética , Plântula/imunologia , Plântula/microbiologia , Sementes/efeitos dos fármacos , Sementes/genética , Sementes/imunologia , Sementes/microbiologia , Superóxido Dismutase/antagonistas & inibidores , Superóxido Dismutase/genética , Superóxido Dismutase/imunologiaRESUMO
l-theanine is a water-soluble non-proteinous amino acid mainly found in green tea leaves. Despite the availability of abundant literature on green tea, studies on the use of l-theanine as a feed additive in animals, and especially broilers are limited. The objective of this study was, therefore, to evaluate the effect of different dietary levels of l-theanine on meat quality, growth performance, immune response, and blood metabolites in broilers. A total of 400 day-old broiler chicks were randomly divided into four treatment groups using a completely randomized design; C-control, basal diet; 100LT-basal diet + 100 mg l-theanine/kg diet; 200LT-basal diet + 200 mg l-theanine/kg diet; and 300LT-basal diet + 300 mg l-theanine/kg diet. Results revealed that the intermediate level of l-theanine (200 mg/kg diet) showed better results in terms of body weight gain (BWG), feed consumed (FC), and feed conversion ratio (FCR) as compared with the other supplemented groups and the control. The live weight eviscerated weight and gizzard weight were higher in all l-theanine levels as compared to those of the control group. Increased weight (p ≤ 0.05) of spleen and bursa were found in group 200LT (200 mg l-theanine/kg diet). Concerning meat color parameters, values for yellowness (b*), and redness (a*) were greater in l-theanine-supplemented groups than the control. Supplementing broiler diet with l-theanine reduced (p = 0.02) total serum cholesterol contents while increased HDL. Further analysis revealed lower relative serum cytokines (IL-2 and INF-γ) and reduced mRNA expression of TNF-α and IL-6 in thymus, and IFN-γ and IL-2 in spleen in the treated group. Moreover, supplementation with 200 mg/kg of l-theanine improved antioxidant status in blood by increasing SOD, GSH-Px, and relative CAT levels. It is concluded that the optimum supplementation level of l-theanine is 200 mg/kg of diet because it resulted in improved performance parameters in broilers. However, higher levels of l-theanine (300 mg/kg diet) may have deleterious effects on performance and health of broiler chickens.
Assuntos
Galinhas/imunologia , Suplementos Nutricionais , Glutamatos/administração & dosagem , Carne/análise , Músculo Esquelético/efeitos dos fármacos , Aumento de Peso/efeitos dos fármacos , Ração Animal/análise , Animais , Bolsa de Fabricius/efeitos dos fármacos , Bolsa de Fabricius/imunologia , Bolsa de Fabricius/metabolismo , Catalase/genética , Catalase/imunologia , Galinhas/genética , Galinhas/crescimento & desenvolvimento , LDL-Colesterol/sangue , Qualidade dos Alimentos , Regulação da Expressão Gênica/imunologia , Glutationa Peroxidase/genética , Glutationa Peroxidase/imunologia , Imunidade Inata/efeitos dos fármacos , Interferon gama/genética , Interferon gama/imunologia , Interleucina-2/genética , Interleucina-2/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Músculo Esquelético/imunologia , Músculo Esquelético/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Baço/efeitos dos fármacos , Baço/imunologia , Baço/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologiaRESUMO
In present study, two hydrolyzed residue polysaccharides (RPS) of enzymatic-RPS (ERPS) and acidic-RPS (ARPS) were successfully obtained from the residue of Lentinula edodes, and the anti-inflammatory as well as antioxidative effects on lipopolysaccharide-induced (LPS-induced) lung injured mice were investigated. The results demonstrated that ERPS showed superior lung protective effects by ameliorating the lung wet-to-dry weight (W/D) ratio, reducing the TNF-α, IL-6, and IL-1ß levels in BALF, lowing the pulmonary MPO activity, decreasing the serum C3 and hs-CPR contents, as well as improving the antioxidant status by enhancing pulmonary enzyme activities (SOD, GSH-Px, CAT, and T-AOC) and eliminating the lipid peroxidation (MDA and LPO), respectively. These conclusions indicated that both RPS and its hydrolysates (ARPS and ERPS) might be suitable for functional foods and a potentially effective candidate medicine for the treatment of lung injury.
Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Edema/tratamento farmacológico , Polissacarídeos Fúngicos/farmacologia , Lesão Pulmonar/tratamento farmacológico , Cogumelos Shiitake/química , Animais , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/isolamento & purificação , Líquido da Lavagem Broncoalveolar/química , Catalase/genética , Catalase/imunologia , Complemento C3/genética , Edema/induzido quimicamente , Edema/imunologia , Edema/patologia , Polissacarídeos Fúngicos/isolamento & purificação , Expressão Gênica , Glutationa Peroxidase/genética , Glutationa Peroxidase/imunologia , Inflamação , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Lipopolissacarídeos/administração & dosagem , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/imunologia , Lesão Pulmonar/patologia , Masculino , Malondialdeído/imunologia , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/genética , Peroxidase/imunologia , Superóxido Dismutase/genética , Superóxido Dismutase/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologiaRESUMO
Objective To evaluate the effect of the phenolic compound naringenin on thermal burn-induced inflammatory responses and oxidative stress in rats. Methods First degree thermal burn injuries were induced in shaved rats by 10 s immersion of the back surface in water at 90â. Naringenin treatment (25, 50 and 100 mg/kg/day) was initiated 24 h following burn injury, and continued for 7 days. On treatment day 7, serum tumour necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, nitric oxide (NO), prostaglandin (PG)E2, caspase-3, leukotriene (LT)-B4 and nuclear factor (NF)-κB levels were quantified. Skin sample glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) levels, and catalase, superoxide dismutase (SOD), glutathione-S-transferase (GST) and glutathione peroxidase (GPx) activities, were also measured. Results Serum inflammatory biomarkers were significantly increased in thermal-burn injured rats versus uninjured controls. Naringenin significantly inhibited the increased proinflammatory markers at day 7 of treatment. Increased TBARS levels and decreased GSH levels in wounded skin were significantly restored by naringenin treatment at day 7. SOD, catalase, GPx and GST activities were markedly inhibited in wounded skin tissues, and were significantly increased in naringenin-treated rats. Conclusion Naringenin treatment showed anti-inflammatory and antioxidant effects in rats with thermal burn-induced injury.
Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Queimaduras/tratamento farmacológico , Flavanonas/farmacologia , Pele/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Animais , Queimaduras/genética , Queimaduras/imunologia , Queimaduras/patologia , Caspase 3/genética , Caspase 3/imunologia , Catalase/genética , Catalase/imunologia , Dinoprostona/biossíntese , Dinoprostona/imunologia , Regulação da Expressão Gênica , Glutationa Peroxidase/genética , Glutationa Peroxidase/imunologia , Glutationa Transferase/genética , Glutationa Transferase/imunologia , Temperatura Alta , Inflamação/prevenção & controle , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Leucotrieno B4/biossíntese , Leucotrieno B4/imunologia , Masculino , NF-kappa B/genética , NF-kappa B/imunologia , Óxido Nítrico/biossíntese , Óxido Nítrico/imunologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Pele/imunologia , Pele/patologia , Superóxido Dismutase/genética , Superóxido Dismutase/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologiaRESUMO
The present study evaluated the ameliorative effects of Trametes orientalis polysaccharide (TOP-2) against cyclophosphamide (CP) induced toxicity in mice. Intraperitoneal administration of TOP-2 not only effectively increased the thymus, spleen, heart, liver, and kidney indices, but also significantly enhanced the phagocytic activities of macrophages and splenocyte proliferation, dose-dependently. The lowered nitric oxide level of macrophages after CP treatment was elevated by TOP-2 administration. Impaired splenic natural killer cells and cytotoxic T lymphocytes activities were remarkably enhanced by TOP-2. Furthermore, the levels of interleukin-2, interferon-γ, Immunoglobulin A, immunoglobulin G, and immunoglobulin M were notably reduced by CP, while TOP-2 abolished these effects. TOP-2 could also effectively increase the total antioxidant capacity, superoxidase dismutase, catalase and glutathione peroxidase activities, and inhibit the increase in malondialdehyde level. These results indicate that TOP-2 may be of therapeutic value in ameliorating the immunosuppression and oxidative stress caused by CP treatment, through its immunomodulatory and antioxidant potential.
Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Ciclofosfamida/antagonistas & inibidores , Polissacarídeos Fúngicos/farmacologia , Imunossupressores/antagonistas & inibidores , Trametes/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Catalase/imunologia , Catalase/metabolismo , Ciclofosfamida/efeitos adversos , Feminino , Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/isolamento & purificação , Glutationa Peroxidase/imunologia , Glutationa Peroxidase/metabolismo , Coração/efeitos dos fármacos , Terapia de Imunossupressão , Imunossupressores/efeitos adversos , Rim/efeitos dos fármacos , Rim/imunologia , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Fígado/efeitos dos fármacos , Fígado/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Malondialdeído/imunologia , Malondialdeído/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Baço/efeitos dos fármacos , Baço/imunologia , Superóxido Dismutase/imunologia , Superóxido Dismutase/metabolismo , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologia , Timo/efeitos dos fármacos , Timo/imunologiaRESUMO
Neutralizing single-domain antibodies directed towards catalase or superoxide dismutase (SOD) caused efficient reactivation of intercellular reactive oxygen species/reactive nitrogen species (ROS/RNS)-dependent apoptosis-inducing signaling specifically in human tumor cells. Single-domain antibodies targeted tumor cell-specific membrane-associated SOD and catalase, but not the corresponding intracellular enzymes. They were shown to be about 200-fold more effective than corresponding classical recombinant antigen-binding fragments and more than four log steps more efficient than monoclonal antibodies. Combined addition of single-domain antibodies against catalase and SOD caused a remarkable synergistic effect. Proof-of-concept experiments in immunocompromised mice using human tumor xenografts and single-domain antibodies directed towards SOD showed an inhibition of tumor growth. Neutralizing single-domain antibodies directed to catalase and SOD also caused a very strong synergistic effect with the established chemotherapeutic agent taxol, indicating an overlap of signaling pathways. This effect might also be useful in order to avoid unwanted side-effects and to drastically lower the costs for taxol-based therapy.
Assuntos
Catalase/imunologia , Proteínas de Membrana/imunologia , Neoplasias/imunologia , Anticorpos de Domínio Único/imunologia , Superóxido Dismutase/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Catalase/antagonistas & inibidores , Humanos , Ratos , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Superóxido Dismutase/antagonistas & inibidoresRESUMO
The present study was carried out to investigate the anti-arthritic activity of Berberis aristata hydroalcoholic extract (BAHE) in formaldehyde-induced arthritis and adjuvant-induced arthritis (AIA) model. Arthritis was induced by administration of either formaldehyde (2% v/v) or CFA into the subplantar surface of the hind paw of the animal. In formaldehyde-induced arthritis and AIA, treatment of BAHE at doses 50, 100 and 200 mg/kg orally significantly decreased joint inflammation as evidenced by decrease in joint diameter and reduced inflammatory cell infiltration in histopathological examination. BAHE treatment demonstrated dose-dependent improvement in the redox status of synovium (decrease in GSH, MDA, and NO levels and increase in SOD and CAT activities). The beneficial effect of BAHE was substantiated with decreased expression of inflammatory markers such as IL-1ß, IL-6, TNF-R1, and VEGF by immunohistochemistry analysis in AIA model. BAHE increased HO-1/Nrf-2 and suppressed NF-κB mRNA and protein expression in adjuvant immunized joint. Additionally, BAHE abrogated degrading enzymes, as there was decreased protein expression of MMP-3 and -9 in AIA. In conclusion, we demonstrated the anti-arthritic activity of Berberis aristata hydroalcoholic extract via the mechanism of inhibition of NF-κB and activation of Nrf-2/HO-1.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Artrite Experimental/tratamento farmacológico , Berberis/química , Heme Oxigenase (Desciclizante)/imunologia , Fator 2 Relacionado a NF-E2/imunologia , NF-kappa B/imunologia , Extratos Vegetais/farmacologia , Administração Oral , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/imunologia , Artrite Experimental/patologia , Catalase/genética , Catalase/imunologia , Relação Dose-Resposta a Droga , Formaldeído , Adjuvante de Freund , Regulação da Expressão Gênica , Glutationa/agonistas , Glutationa/imunologia , Goma Arábica , Heme Oxigenase (Desciclizante)/genética , Masculino , Malondialdeído/antagonistas & inibidores , Malondialdeído/imunologia , Fator 2 Relacionado a NF-E2/genética , NF-kappa B/genética , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/imunologia , Ratos , Ratos Wistar , Transdução de Sinais , Superóxido Dismutase/genética , Superóxido Dismutase/imunologia , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/imunologia , Membrana Sinovial/patologia , Tarso Animal/efeitos dos fármacos , Tarso Animal/imunologia , Tarso Animal/patologiaRESUMO
AIM: To investigate catalase (KatA) and alkyl hydroperoxide reductase (AhpC) antibodies of Helicobacter pylori as biomarkers for gastric cancer (GC). METHODS: This study included 232 cases and 264 controls. Recombinant KatA and AhpC proteins were constructed and the levels of antibodies were tested by indirect enzyme-linked immunosorbent assay (ELISA). Logistic regression was applied to analyze the relationships between KatA, AhpC and GC. The χ(2) trend test was used to evaluate the dose-response relationships between serum KatA and AhpC antibody levels and GC. Receiver operating characteristic (ROC) curve was used to evaluate the screening accuracy of KatA and AhpC as biomarkers. Combined analysis was used to observe screening accuracy of predictors for GC. RESULTS: In all subjects, the association between KatA and AhpC and GC risk was significant (P < 0.001) with odds ratio (OR) = 12.84 (95%CI: 7.79-21.15) and OR = 2.4 (95%CI: 1.55-3.73), respectively. KatA and AhpC antibody levels were strongly related to GC risk with a dose-dependent effect (P for trend < 0.001). The area under the ROC (AUC) for KatA was 0.806, providing a sensitivity of 66.81% and specificity of 86.36%; and the AUC for AhpC was 0.615, with a sensitivity of 75.65% and specificity of 45.49%. The AUC was 0.906 for KatA and flagella protein A (FlaA) combined analysis. CONCLUSION: Serum KatA and AhpC antibodies are associated with GC risk and KatA may serve as a biomarker for GC. KatA/FlaA combined analysis improved screening accuracy.
Assuntos
Anticorpos Antibacterianos/sangue , Proteínas de Bactérias/imunologia , Biomarcadores Tumorais/sangue , Catalase/imunologia , Infecções por Helicobacter/sangue , Helicobacter pylori/imunologia , Peroxidases/imunologia , Neoplasias Gástricas/sangue , Área Sob a Curva , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Ensaio de Imunoadsorção Enzimática , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/microbiologia , Humanos , Modelos Logísticos , Razão de Chances , Valor Preditivo dos Testes , Curva ROC , Reprodutibilidade dos Testes , Testes Sorológicos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/microbiologiaRESUMO
Treatment of cancer patients by adoptive T cell therapy has yielded promising results. In solid tumors, however, T cells encounter a hostile environment, in particular with increased inflammatory activity as a hallmark of the tumor milieu that goes along with abundant reactive oxygen species (ROS) that substantially impair antitumor activity. We present a strategy to render antitumor T cells more resilient toward ROS by coexpressing catalase along with a tumor specific chimeric Ag receptor (CAR) to increase their antioxidative capacity by metabolizing H2O2. In fact, T cells engineered with a bicistronic vector that concurrently expresses catalase, along with the CAR coexpressing catalase (CAR-CAT), performed superior over CAR T cells as they showed increased levels of intracellular catalase and had a reduced oxidative state with less ROS accumulation in both the basal state and upon activation while maintaining their antitumor activity despite high H2O2 levels. Moreover, CAR-CAT T cells exerted a substantial bystander protection of nontransfected immune effector cells as measured by CD3ζ chain expression in bystander T cells even in the presence of high H2O2 concentrations. Bystander NK cells, otherwise ROS sensitive, efficiently eliminate their K562 target cells under H2O2-induced oxidative stress when admixed with CAR-CAT T cells. This approach represents a novel means for protecting tumor-infiltrating cells from tumor-associated oxidative stress-mediated repression.
Assuntos
Catalase/imunologia , Imunoterapia Adotiva/métodos , Células Matadoras Naturais/imunologia , Estresse Oxidativo/fisiologia , Linfócitos T/imunologia , Western Blotting , Efeito Espectador/imunologia , Linhagem Celular , Separação Celular , Humanos , Receptores de Antígenos de Linfócitos T/imunologia , Proteínas Recombinantes de Fusão/imunologia , TransfecçãoRESUMO
As an innate defense mechanism, macrophages produce reactive oxygen species that weaken pathogens and serve as secondary messengers involved in immune function. The Gram-negative bacterium Francisella tularensis utilizes its antioxidant armature to limit the host immune response, but the mechanism behind this suppression is not defined. Here we establish that F. tularensis limits Ca(2+) entry in macrophages, thereby limiting actin reorganization and IL-6 production in a redox-dependent fashion. Wild type (live vaccine strain) or catalase-deficient F. tularensis (ΔkatG) show distinct profiles in their H2O2 scavenging rates, 1 and 0.015 pm/s, respectively. Murine alveolar macrophages infected with ΔkatG display abnormally high basal intracellular Ca(2+) concentration that did not increase further in response to H2O2. Additionally, ΔkatG-infected macrophages displayed limited Ca(2+) influx in response to ionomycin, as a result of ionophore H2O2 sensitivity. Exogenously added H2O2 or H2O2 generated by ΔkatG likely oxidizes ionomycin and alters its ability to transport Ca(2+). Basal increases in cytosolic Ca(2+) and insensitivity to H2O2-mediated Ca(2+) entry in ΔkatG-infected cells are reversed by the Ca(2+) channel inhibitors 2-aminoethyl diphenylborinate and SKF-96365. 2-Aminoethyl diphenylborinate but not SKF-96365 abrogated ΔkatG-dependent increases in macrophage actin remodeling and IL-6 secretion, suggesting a role for H2O2-mediated Ca(2+) entry through the transient receptor potential melastatin 2 (TRPM2) channel in macrophages. Indeed, increases in basal Ca(2+), actin polymerization, and IL-6 production are reversed in TRPM2-null macrophages infected with ΔkatG. Together, our findings provide compelling evidence that F. tularensis catalase restricts reactive oxygen species to temper macrophage TRPM2-mediated Ca(2+) signaling and limit host immune function.
Assuntos
Proteínas de Bactérias/imunologia , Catalase/imunologia , Francisella tularensis/imunologia , Imunidade Inata , Macrófagos/imunologia , Canais de Cátion TRPM/imunologia , Tularemia/imunologia , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Cálcio/imunologia , Cálcio/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Sinalização do Cálcio/imunologia , Catalase/genética , Catalase/metabolismo , Feminino , Francisella tularensis/enzimologia , Francisella tularensis/genética , Deleção de Genes , Peróxido de Hidrogênio/imunologia , Peróxido de Hidrogênio/metabolismo , Interleucina-6/genética , Interleucina-6/imunologia , Interleucina-6/metabolismo , Ionomicina/farmacologia , Macrófagos/metabolismo , Macrófagos/microbiologia , Camundongos , Camundongos Knockout , Oxirredução/efeitos dos fármacos , Canais de Cátion TRPM/genética , Canais de Cátion TRPM/metabolismo , Tularemia/genética , Tularemia/metabolismoRESUMO
Dendritic cells (DCs) play a vital role in the regulation of immune-mediated inflammatory diseases. Thus, DCs have been regarded as a major target for the development of immunomodulators. However, oxidative stress could disturb inflammatory regulation in DCs. Here, we examined the effect of bursopentine (BP5), a novel pentapeptide isolated from chicken bursa of fabricius, on the protection of DCs against oxidative stress for immunosuppression. BP5 showed potent protective effects against the lipopolysaccharide (LPS)-induced oxidative stress in DCs, including nitric oxide, reactive oxygen species and lipid peroxidation. Furthermore, BP5 elevated the level of cellular reductive status through increasing the reduced glutathione (GSH) and the GSH/GSSG ratio. Concomitant with these, the activities of several antioxidative redox enzymes, including glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD), were obviously enhanced. BP5 also suppressed submucosal DC maturation in the LPS-stimulated intestinal epithelial cells (ECs)/DCs coculture system. Finally, we found that heme oxygenase 1 (HO-1) was remarkably upregulated by BP5 in the LPS-induced DCs, and played an important role in the suppression of oxidative stress and DC maturation. These results suggested that BP5 could protect the LPS-activated DCs against oxidative stress and have potential applications in DC-related inflammatory responses.