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1.
Stress ; 27(1): 2319803, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38628154

RESUMO

Heat stress has been ranked as a critical environmental issue confronting chicken farmers worldwide because of its detrimental effect on the growth, performance and health of the birds. This study evaluated the effects of early-age thermal manipulation (EATC) and supplemental antioxidants on the physiological responses of broilers in a hot tropical environment. A total of 300 day-old Ross broiler chicks were allocated to five thermal and dietary treatments, having 5 replicates of twelve birds each. The treatments were: chicks reared using the conventional method (CC), chicks exposed to early thermal manipulation with a temperature of 38 °C at day 5 with no antioxidant supplementation (TC), TC plus vitamin E at 250 mg/kg of feed (TV), TC plus selenium at 0.5 mg/kg of feed (TS) and the combination of TS and TV(TVS). The experiment was laid out in a Completely Randomized Design and data collected were analyzed using SAS (2008). The results showed that TVS broilers had significantly higher (P < 0.05) body weights at the finisher phase than the other treatment groups. The feed conversion ratio of TVS broilers was comparable to the TV group but lower (P < 0.05) than the other treatments. Reduced levels (P < 0.05) of heterophil, lymphocytes and hetrophil and lymphocyte ratio were recorded in the TVS compared to TV, TS and TC broilers. On day 42, the rectal temperature was significantly higher in CC than those in other treatment groups, which were comparable. TVS birds had higher (P < 0.05) weights of spleen, liver and lower abdominal fat than other treatments. The lowest concentration of plasma malondialdehyde and the highest activity of superoxide dismutase and glutathione peroxidase were recorded in TV and TVS birds. The study concluded that the growth performance and oxidative status in broilers were improved by the combination of EATC with supplemental Se and vitamin E (TVS).


Assuntos
Antioxidantes , Galinhas , Animais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Galinhas/fisiologia , Dieta/veterinária , Suplementos Nutricionais , Estresse Psicológico , Vitamina E/farmacologia
2.
Sci Rep ; 14(1): 5757, 2024 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459144

RESUMO

Despite remarkable scientific progress over the past six decades within the medical arts and in radiobiology in general, limited radiation medical countermeasures (MCMs) have been approved by the United States Food and Drug Administration for the acute radiation syndrome (ARS). Additional effort is needed to develop large animal models for improving the prediction of clinical safety and effectiveness of MCMs for acute and delayed effects of radiation in humans. Nonhuman primates (NHPs) are considered the animal models that reproduce the most appropriate representation of human disease and are considered the gold standard for drug development and regulatory approval. The clinical and histopathological effects of supralethal, total- or partial-body irradiations (12 Gy) of NHPs were assessed, along with possible protective actions of a promising radiation MCM, gamma-tocotrienol (GT3). Results show that these supralethal radiation exposures induce severe injuries that manifest both clinically as well as pathologically, as evidenced by the noted functionally crippling lesions within various major organ systems of experimental NHPs. The MCM, GT3, has limited radioprotective efficacy against such supralethal radiation doses.


Assuntos
Síndrome Aguda da Radiação , Cromanos , Contramedidas Médicas , Protetores contra Radiação , Vitamina E/análogos & derivados , Animais , Estados Unidos , Humanos , Vitamina E/farmacologia , Síndrome Aguda da Radiação/tratamento farmacológico , Síndrome Aguda da Radiação/patologia , Modelos Animais de Doenças , Protetores contra Radiação/farmacologia , Macaca mulatta
3.
Molecules ; 29(5)2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38474668

RESUMO

Anthracycline antibiotics, namely, doxorubicin (DOX) and daunorubicin, are among the most widely used anticancer therapies, yet are notoriously associated with severe myocardial damage due to oxidative stress and mitochondrial damage. Studies have indicated the strong pharmacological properties of Berberine (Brb) alkaloid, predominantly mediated via mitochondrial functions and nuclear networks. Despite the recent emphasis on Brb in clinical cardioprotective studies, pharmaceutical limitations hamper its clinical use. A nanoformulation for Brb was developed (mMic), incorporating a cationic lipid, oleylamine (OA), into the TPGS-mixed corona of PEGylated-phosphatidylethanolamine (PEG-PE) micelles. Cationic TPGS/PEG-PE mMic with superior Brb loading and stability markedly enhanced both intracellular and mitochondria-tropic Brb activities in cardiovascular muscle cells. Sub-lethal doses of Brb via cationic OA/TPGS mMic, as a DOX co-treatment, resulted in significant mitochondrial apoptosis suppression. In combination with an intense DOX challenge (up to ~50 µM), mitochondria-protective Brb-OA/TPGS mMic showed a significant 24 h recovery of cell viability (p ≤ 0.05-0.01). Mechanistically, the significant relative reduction in apoptotic caspase-9 and elevation of antiapoptotic Bcl-2 seem to mediate the cardioprotective role of Brb-OA/TPGS mMic against DOX. Our report aims to demonstrate the great potential of cationic OA/TPGS-mMic to selectively enhance the protective mitohormetic effect of Brb to mitigate DOX cardiotoxicity.


Assuntos
Berberina , Doenças Mitocondriais , Fosfatidiletanolaminas , Polietilenoglicóis , Humanos , Micelas , Berberina/farmacologia , Cardiotoxicidade/tratamento farmacológico , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Vitamina E/farmacologia , Apoptose , Doenças Mitocondriais/tratamento farmacológico
4.
Environ Int ; 185: 108547, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38458120

RESUMO

Cadmium (Cd) is a toxic heavy metal associated with osteoporosis, liver, and kidney disease. The black soldier fly (BSF) Hermetia illucens may be exposed to Cd during the transformation of livestock manure. The BSF has a high tolerance to Cd. In the previous work of the laboratory, we found that vitamin E (VE) may play a role in the tolerance of BSF to Cd exposure. The main findings are as follows: The BSF larvae pretreated with exogenous VE had heavier body weight, lower content and toxicity of Cd under similar Cd exposure. Even in high Cd exposure at the concentrations of 300 and 700 mg/kg, the BSF larvae pretreated with exogenous VE at a concentration of 100 mg/kg still reduced the Cd toxicity to 85.33 % and 84.43 %, respectively. The best-fitting models showed that metallothionein (MT) content, oxidative damage (8-hydroxydeoxyguanosine content, malondialdehyde content), antioxidant power (total antioxidant power, peroxidase activity) had a great influence on content and toxicity of Cd bioaccumulated in the larvae. The degree of oxidative damage was reduced in the larvae with exogenous VE pretreatments. This variation can be explained by their changed MT content and increased antioxidant power because of exogenous VE. These results reveal the roles of VE in insects defense against Cd exposure and provide a new option for the prevention and therapy of damage caused by Cd exposure.


Assuntos
Cádmio , Dípteros , Animais , Cádmio/toxicidade , Vitamina E/farmacologia , Antioxidantes , Larva
5.
Sci Rep ; 14(1): 6977, 2024 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-38521858

RESUMO

Radiation-induced renal fibrosis (RIRF) is a progressive, irreversible condition causing chronic kidney disease. Pentoxifylline (PTX) and vitamin E may mitigate radiation-induced damage and fibrosis. This study assesses their effectiveness. We used four groups, each with six rats: radiation therapy alone (RT-only), radiation therapy plus drug treatment (RT + drug), drug treatment alone (drug-only), and a control group. Rats were monitored for three months, with weight measurements every four weeks. Afterward, rats were analyzed biochemically and histologically, with blood and tissue samples taken for statistical comparison. No significant differences in serum creatinine levels and body weight were observed. RT-only group had more severe kidney tubule effects. Histomorphological, immunohistochemical, and TUNEL analyses showed significant RIRF mitigation in the RT + drug group. Our study highlighted molecular pathways (SMAD, TGF-beta, VEGF) and histological markers (collagens, a-SMA, fibronectin, metalloproteinases) associated with RIRF. PTX and vitamin E reduced ionizing radiation's impact on renal cells and mitigated radiation-induced kidney fibrosis. Further human studies are needed to confirm these findings.


Assuntos
Pentoxifilina , Ratos , Humanos , Animais , Pentoxifilina/farmacologia , Pentoxifilina/uso terapêutico , Vitamina E/farmacologia , Vitamina E/uso terapêutico , Antioxidantes/farmacologia , Rim/patologia , Fibrose
6.
Anim Biotechnol ; 35(1): 2331640, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38526422

RESUMO

The present study was carried out to evaluate the effects of dietary vitamin E (VE) or grape seed extract (GSE) on the growth performance and antioxidant function of broilers. Two hundred sixteen broiler chicks were randomly assigned to 3 diets: diet supplemented with oxidized rice bran oil (CN group), CN group with 25 mg/kg VE or 100 mg/kg GSE. Dietary VE or GSE improved the growth performance, reverted the disturbed levels of liver antioxidant enzymes, and reduced liver damage of broilers fed oxidized rice bran oil. The mRNA data showed that supplementation of VE or GSE enhanced the antioxidant capacity of the broiler liver through activation of the Keap1-Nrf2/ARE signaling pathway. The results suggested that VE and GSE can increase weight gain, improve the oxidative status, and alleviate liver injury in broiler chicken fed oxidized rice bran oil.


Assuntos
Antioxidantes , Extrato de Sementes de Uva , Animais , Antioxidantes/farmacologia , Vitamina E/farmacologia , Extrato de Sementes de Uva/farmacologia , Galinhas , Proteína 1 Associada a ECH Semelhante a Kelch , Óleo de Farelo de Arroz , Fator 2 Relacionado a NF-E2 , Suplementos Nutricionais
7.
J Integr Med ; 22(1): 1-11, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38336507

RESUMO

Tocotrienols are found in a variety of natural sources, like rice bran, annatto seeds and palm oil, and have been shown to have several health-promoting properties, particularly against chronic diseases such as cancer. The incidence of cancer is rapidly increasing around the world, not only a result of continued aging and population growth, but also due to the adoption of aspects of the Western lifestyle, such as high-fat diets and low-physical activity. The literature provides strong evidence that tocotrienols are able to inhibit the growth of various cancers, including breast, lung, ovarian, prostate, liver, brain, colon, myeloma and pancreatic cancers. These findings, along with the reported safety profile of tocotrienols in healthy human volunteers, encourage further research into these compounds' potential use in cancer prevention and treatment. The current review provided detailed information about the molecular mechanisms of action of different tocotrienol isoforms in various cancer models and evaluated the potential therapeutic effects of different vitamin E analogues on important cancer hallmarks, such as cellular proliferation, apoptosis, angiogenesis and metastasis. MEDLINE/PubMed and Scopus databases were used to identify recently published articles that investigated the anticancer effects of vitamin E derivatives in various types of cancer in vitro and in vivo along with clinical evidence of adjuvant chemopreventive benefits. Following an overview of pre-clinical studies, we describe several completed and ongoing clinical trials that are paving the way for the successful implementation of tocotrienols in cancer chemotherapy.


Assuntos
Neoplasias , Tocotrienóis , Humanos , Antioxidantes/farmacologia , Apoptose , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Tocotrienóis/farmacologia , Tocotrienóis/uso terapêutico , Vitamina E/farmacologia , Vitamina E/uso terapêutico , Ensaios Clínicos como Assunto
8.
Nucl Med Commun ; 45(4): 312-320, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38312062

RESUMO

OBJECTIVE: This study aimed to evaluate the effects of three antioxidants, selenium yeast capsule, vitamin E and vitamin C, alone or in combination, on the salivary glands of patients with differentiated thyroid cancer (DTC) treated with iodine-131 ( 131 I). METHODS: A total of 69 postoperative DTC patients were randomly divided into three groups: vitamin E combined with vitamin C group (21 cases); selenium yeast group (23 cases); and selenium yeast combined with vitamin C group (25 cases). Salivary gland functional changes were assessed by salivary gland dynamic imaging functional parameters in the enrolled patients before and 1 month after 131 I treatment. RESULTS: Comparison of salivary gland function parameters before and after 131 I treatment in the three groups were evaluated. In the vitamin E combined with the vitamin C group, the left parotid gland excretion fraction (EF) value was significantly higher than that before treatment. In the selenium yeast group, the left parotid gland excretion part, bilateral parotid gland excretion ratio (ER), left submandibular gland maximum uptake ratio within 20 min (UR20), and the right submandibular gland ER values were significantly higher than that before treatment, while in the selenium yeast combined with vitamin C group, the bilateral parotid gland EF, bilateral submandibular gland UR20, EF, and left submandibular gland ER values were significantly higher than that before treatment (all P < 0.05). CONCLUSION: During high-dose 131 I treatment, vitamin E combined with vitamin C improved the excretory function of parotid glands in DTC patients; selenium supplementation had a protective effect on salivary glands; and the combination of selenium and vitamin C had a better effect.


Assuntos
Selênio , Neoplasias da Glândula Tireoide , Humanos , Radioisótopos do Iodo/uso terapêutico , Antioxidantes/uso terapêutico , Antioxidantes/farmacologia , Selênio/farmacologia , Selênio/uso terapêutico , Saccharomyces cerevisiae , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Glândulas Salivares , Glândula Parótida , Vitamina E/farmacologia , Vitamina E/uso terapêutico , Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico
9.
Toxicology ; 502: 153729, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38242491

RESUMO

Acrylamide (ACR), a toxin present in fried and baked carbohydrate-rich foods, is known to cause liver and kidney damage. This study aimed to investigate the mechanisms of oxidative stress, inflammation, and apoptosis that contribute to liver and kidney damage induced by chronic administration of ACR. Additionally, the effectiveness of vitamin E in mitigating these toxic effects was examined. The study initially involved dividing 40 pregnant rats into four groups. After lactation, the research continued with male offspring rats from each group. The offspring rats were divided into Control, Vitamin E, ACR, and ACR + Vitamin E groups. Following ACR administration, liver and kidney function tests were performed on serum samples. Biochemical analyses, evaluation of inflammation markers, histopathological examination, and assessment of protein levels of Akt/IκBα/NF-κB, Bax, Bcl-xL, and Caspase-9 were conducted on liver and kidney tissues. The analysis demonstrated that ACR adversely affected liver and kidney function, resulting in oxidative stress, increased inflammation, and elevated apoptotic markers. Conversely, administration of vitamin E positively impacted these parameters, restoring them to control levels. Based on the results, the mechanism of ACR's action on oxidative stress and inflammation-induced liver and kidney damage may be associated with the activation of apoptotic markers such as Bax and Caspase-9, as well as the Akt/IκBα/NF-κB signaling pathway. Consequently, the protective properties of vitamin E establish it as an essential vitamin for the prevention or mitigation of various ACR-induced damages.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , NF-kappa B , Feminino , Ratos , Masculino , Animais , NF-kappa B/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , Inibidor de NF-kappaB alfa/farmacologia , Proteína X Associada a bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Caspase 9/metabolismo , Vitamina E/farmacologia , Vitamina E/uso terapêutico , Acrilamida/toxicidade , Transdução de Sinais , Estresse Oxidativo , Inflamação , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Desenvolvimento Fetal , Apoptose , Antioxidantes/farmacologia
10.
Radiat Res ; 201(1): 55-70, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38059553

RESUMO

Currently, no radioprotectors have been approved to mitigate hematopoietic injury after exposure to ionizing radiation. Acute ionizing radiation results in damage to both hematopoietic and immune system cells. Pre-exposure prophylactic agents are needed for first responders and military personnel. In this study, the ability of gamma-tocotrienol (GT3), a promising radioprotector and antioxidant, to ameliorate partial-body radiation-induced damage to the hematopoietic compartment was evaluated in a nonhuman primate (NHP) model. A total of 15 rhesus NHPs were divided into two groups, and were administered either GT3 or vehicle 24 h prior to 4 or 5.8 Gy partial-body irradiation (PBI), with 5% bone marrow (BM) sparing. Each group consisted of four NHPs, apart from the vehicle-treated group exposed to 5.8 Gy, which had only three NHPs. BM samples were collected 8 days prior to irradiation in addition to 2, 7, 14, and 30 days postirradiation. To assess the clonogenic ability of hematopoietic stem and progenitor cells (HSPCs), colony forming unit (CFU) assays were performed, and lymphoid cells were immunophenotyped using flow cytometry. As a result of GT3 treatment, an increase in HSPC function was evident by an increased recovery of CFU-granulocyte macrophages (CFU-GM). Additionally, GT3 treatment was shown to increase the percentage of CD34+ cells, including T and NK-cell subsets. Our data further affirm GT3's role in hematopoietic recovery and suggest the need for its further development as a prophylactic radiation medical countermeasure.


Assuntos
Cromanos , Protetores contra Radiação , Animais , Macaca mulatta , Protetores contra Radiação/farmacologia , Vitamina E/farmacologia , Medula Óssea/efeitos da radiação
11.
Environ Sci Pollut Res Int ; 31(2): 2156-2166, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38055172

RESUMO

This study was planned to detect the adverse pathological consequences of aflatoxin B1 in White Leghorn (WLH) layer breeder males. Eight-week-old male layer cockerels were separated into six experimental categories: A group was kept as negative control, offered with normal feed only; group B was fed with 400 ppb amount of aflatoxin, while groups F and D fed with normal feed and supplemented with vitamin E 100 ppm and 1% Moringa oleifera, respectively, whereas groups E and C were fed with 400 ppb aflatoxin containing feed and ameliorated with vitamin E 100 ppm and 1% Moringa oleifera, respectively. This study was continued for 2 months and immunologic disorders and reproductive parameters were observed during the trial. To find out immunological status lymphoproliferative response to phytohemagglutinin-P (PHA-P), antibody titers against sheep red blood cells (SRBCs) and carbon clear assay were performed by collecting samples from five birds from each group. The whole data was measured by ANOVA test, and group means were compared by DMR test by using M-Stat C software. Regarding the reproductive status, spermatogenesis, blood testosterone level, testes weight, testes histology, sperm motility, and morphology were negatively affected by aflatoxins, but these deviations positively ameliorated by vitamin E and Moringa. Vitamin E and Moringa found advantageous in boosting the immune status of affected bird. All the immunological parameters including antibody titers against sheed red blood cells, lymphoproliferative response to avian tuberculin and phagocytic potential of macrophages were suppressed by AFB1 however in control, Moringa and vitamin E groups these immunological responses were significantly higher.


Assuntos
Aflatoxinas , Moringa oleifera , Animais , Masculino , Ração Animal/análise , Galinhas , Motilidade dos Espermatozoides , Tocoferóis , Vitamina E/farmacologia
12.
Int J Pharm ; 649: 123669, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38056797

RESUMO

Multidrug resistance (MDR) is a public health issue of particular concern, for which nanotechnology-based multidrug delivery systems are considered among the most effective suppressive strategies for such resistance in tumors. However, for such strategies to be viable, the notable shortcomings of reduced loading efficiency and uncontrollable drug release ratio need to be addressed. To this end, we developed a novel "multidrug/material" co-delivery system, using d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS, P-gp efflux pump inhibitor) and poly(amidoamine) (PAMAM) to fabricate a precursor material with the properties of reversing MDR and having a long-cycle. Further, to facilitate multidrug co-delivery, we loaded doxorubicin(Dox) and curcumin(Cur, cardiotoxicity modifier and P-gp inhibitor) into PAMAM-TPGS nano-micelles respectively, and mixed in appropriate proportions. The multidrug/material co-delivery system thus obtained was characterized by high drug loading and a controllable drug release ratio in the physiological environment. More importantly, in vitro and in vivo pharmacodynamic studies indicated that the multidrug/material co-delivery system facilitated the reversal of MDR. Moreover, the system has increased anti-tumor activity and is biologically safe. We accordingly propose that the "multidrug/material" co-delivery system developed in this study could serve as a potential platform for reversing MDR and achieving safe and effective clinical treatment.


Assuntos
Antineoplásicos , Resistencia a Medicamentos Antineoplásicos , Humanos , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Resistência a Múltiplos Medicamentos , Micelas , Vitamina E/farmacologia , Polietilenoglicóis/farmacologia , Antineoplásicos/farmacologia , Células MCF-7
13.
Cancer Chemother Pharmacol ; 93(3): 215-224, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37926754

RESUMO

PURPOSE: In addition to peripheral neuronal dysfunction, conventional chemotherapy can be associated with other neurological treatment-limiting adverse effects, including cognitive dysfunction, memory impairment, and anxiety, which are referred to as "chemobrain". This study aimed to investigate the effects of doxorubicin (DOX) and paclitaxel (PAC) on learning and memory in rats using radial arm water maze (RAWM) and investigated a potential beneficial effect of vitamin E (Vit. E). METHODS: Adult male rats were injected with four doses of 2 mg/kg/week DOX, or 2 mg/kg PAC every other day intraperitoneally. Vit. E was co-administered with these drugs in other groups to study its antioxidative effects. Using the RAWM, each rat was assessed for learning and memory performance through two sets of six trials separated by a 5-min rest period evaluating both short- and long-term effects on memory. RESULTS: There was no deficit in learning or long-term memory in both drug groups compared to control. However, rats in both drug groups made significantly more errors in all short-term memory trials. This effect was mitigated when Vit. E was co-administered with either drug. Moreover, PAC (but not DOX) induced hippocampal lipid peroxidation by increasing the levels of standard biomarker thiobarbituric acid reactive substances (TBARS). Interestingly, Vit. E prevented PAC-induced hippocampal oxidative stress. Furthermore, both DOX and PAC were correlated with reduction in Brain-Derived Neurotrophic Factor (BDNF) expression levels in the hippocampus, which was overcome by the co-administration of Vit. E. CONCLUSION: There is a potential role of Vit. E in alleviating short-term memory impairment in rats exposed to chemotherapy, possibly by reducing hippocampal oxidative stress and neurodegeneration.


Assuntos
Paclitaxel , Vitamina E , Ratos , Masculino , Animais , Vitamina E/farmacologia , Vitamina E/uso terapêutico , Paclitaxel/toxicidade , Ratos Wistar , Antioxidantes , Estresse Oxidativo , Doxorrubicina/toxicidade , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/prevenção & controle
14.
Naunyn Schmiedebergs Arch Pharmacol ; 397(2): 829-841, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37515736

RESUMO

Acrylamide (ACR) is a toxic chemical frequently encountered in daily life, posing health risks. This study aimed to elucidate the molecular-level mechanism of ACR's toxic effects on testicles and investigate whether Vitamin E can mitigate these effects. A total of 40 adult pregnant rats were utilized, divided into four groups: Control, ACR, Vitamin E, and ACR + Vitamin E. ACR and Vitamin E were administered to the mother rats during pregnancy and lactation, and to the male offspring until the 8th week post-birth. Serum hormone levels, oxidant-antioxidant parameters, histopathological examination of testicular tissue, and mRNA and protein levels of the testicular and liver aromatase gene were analyzed. Spermiogram analysis was conducted on the collected sperm samples from the male offspring. The results revealed that ACR exposure adversely affected hormone levels, oxidant-antioxidant parameters, histological findings, as well as aromatase gene and protein expressions. However, Vitamin E administration effectively prevented the toxic effects of ACR. These findings demonstrate that ACR application significantly impairs the reproductive performance of male offspring rats by increasing liver aromatase activity.


Assuntos
Antioxidantes , Vitamina E , Gravidez , Feminino , Ratos , Masculino , Animais , Vitamina E/farmacologia , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Testículo , Acrilamida/toxicidade , Acrilamida/metabolismo , Aromatase/genética , Aromatase/metabolismo , Aromatase/farmacologia , Sêmen/metabolismo , Estresse Oxidativo , Oxidantes/metabolismo , Oxidantes/farmacologia , Hormônios/farmacologia
15.
Biomed Pharmacother ; 170: 116078, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38159375

RESUMO

PD-L1-mediated immune escape plays an important role in cancer development and progression. Targeting PD-L1 is consider to be an attractive approach for cancer treatment. PD-L1 is a heavily N-linked glycosylated protein, and the glycosylation of PD-L1 is essential for its ability to interact with its receptor PD-1 to mediate immune suppression. In the present study, we demonstrated for the first time that delta-tocotrienol (δ-T3) not any of the other forms of vitamin E was able to disrupt PD-L1 glycosylation mechanistically associated with the suppression of TCF4-STT3a/STT3b axis. The inhibition of PD-L1 glycosylation by δ-T3 resulted in the decrease of PD-L1 expression and its exosomal secretion, leading to the reduction of PD-L1 and PD-1 interaction, and reversing PD-L1-mediated immune suppression, which in turn contributed to the inhibitory effect on tumor growth. The findings of the present study provide a novel mechanistic interpretation for the superior anticancer activity of δ-T3 among 8 isomers of the vitamin E.


Assuntos
Antígeno B7-H1 , Receptor de Morte Celular Programada 1 , Linhagem Celular Tumoral , Glicosilação , Antígeno B7-H1/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Vitamina E/farmacologia
16.
Int. j. morphol ; 41(6): 1596-1602, dic. 2023. ilus
Artigo em Espanhol | LILACS | ID: biblio-1528809

RESUMO

El ácido valproico (VPA) es un fármaco antiepiléptico teratógenico que, al ser administrado durante etapas tempranas del embarazo, puede producir alteraciones en el desarrollo embriofetal, las que se manifiestan tanto a nivel del sistema nervioso como del testículo. No obstante, se ha reportado que la administración de vitamina E (VE) podría revertir dichas alteraciones. El objetivo del presente estudio fue determinar el efecto protector de la VE a nivel testicular en fetos y ratones púberes expuestos a VPA durante la fase embrionaria de su desarrollo. Se utilizó un total de 30 ratones hembra adultas gestantes (Mus musculus) cepa BALB/c, las cuales se dividieron en 6 grupos. El estudio contempló el análisis de fetos machos a los 17,5 días post-coital (dpc) y machos juveniles a las 6 semanas post-natal. A los grupos 1 y 4 se les administró 0,3 mL de solución fisiológica (grupos control para 17,5 dpc y 6 semanas postnatal, respectivamente). A los grupos 2 y 5 se les suministró la cantidad de 600 mg/kg de VPA (grupos VPA), en tanto que a los grupos 3 y 6 se les aplicó la misma dosis de VPA complementada con 200 UI de VE (grupos VPA+VE). Se describió la histología normal y patológica del compartimento peritubular del testículo. En los grupos VPA se evidenció una degeneración de la pared peritubular, y atrofia de túbulos seminíferos, así como exfoliación de las células germinales. Por el contrario, en los grupos VPA+VE tales signos no fueron observados y la morfología presentó aspecto normal solo con algunas alteraciones focales. Estos resultados corroboran el hecho que la administración de VE contrarresta en parte, los efectos deletéreos que ocasiona el VPA.


SUMMARY: Valproic acid (VPA) is a teratogenic antiepileptic drug that, when administered during the early stages of pregnancy, can produce alterations in embryo-fetal development, which manifest both at the level of the nervous system and the testicle. However, it has been reported that the administration of vitamin E (VE) could reverse these alterations. The study aimed to determine the protective effect of VE at the testicular level in fetuses and pubertal mice exposed to VPA during the embryonic phase of their development. 30 pregnant adult female mice (Mus musculus) BALB/c strain were used, which were divided into 6 groups. The study included the analysis of male fetuses at 17.5 days post-coital (dpc) and juvenile males at 6 weeks post-natal. Groups 1 and 4 were administered 0.3 mL of physiological solution. Groups 2 and 5 were given 600 mg/kg of VPA (VPA groups), while groups 3 and 6 were given the same dose of VPA supplemented with 200 IU of VE (VPA+VE). The normal and pathological histology of the peritubular compartment of the testis was described. In the VPA groups, degeneration of the peritubular wall, and atrophy of the seminiferous tubules, as well as exfoliation of the germ cells, were evident. On the contrary, in the VPA+VE groups such signs were not observed and the morphology presented a normal appearance with only some focal alterations. These results corroborate the fact that the administration of VE partially counteracts the deleterious effects caused by VPA.


Assuntos
Animais , Feminino , Gravidez , Camundongos , Testículo/efeitos dos fármacos , Vitamina E/administração & dosagem , Ácido Valproico/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Túbulos Seminíferos/citologia , Túbulos Seminíferos/efeitos dos fármacos , Testículo/citologia , Vitamina E/farmacologia , Camundongos Endogâmicos BALB C , Anticonvulsivantes/toxicidade
17.
J Anim Sci ; 1012023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-37933958

RESUMO

This study aimed to investigate the effects of diets supplemented with 25-hydroxycholecalciferol [25-(OH)D3] and additional vitamin E on growth performance, antioxidant capacity, bone development, and carcass characteristics at different stocking densities on commercial broiler farms. A total of 118,800 one-day-old Arbor Acres broilers were assigned to a 2 × 2 factorial treatment consisting of two dietary vitamin levels (5,500 IU vitamin D3 and 60 IU vitamin E: normal diet, using half 25-(OH)D3 as a source of vitamin D3 and an additional 60 IU of vitamin E: 25-(OH)D3+VE diet) and two stocking densities (high density of 20 chickens/m2: HD and 16 chickens/m2: LD). The experiment lasted for 42 d. The results showed that high-density stocking negatively affected the growth performance of broilers during the first four weeks, whereas the vitamin diet treatment significantly improved the feed conversion ratios (FCR) during the last 2 wk. Vitamin diets increased catalase at 14 and 42 d, and the glutathione peroxidase (GSH-px) levels at 42 d in high-density-stocked broilers. The interaction showed that serum vitamin E levels were significantly improved at 28 d of age in high-density-stocked broilers as a result of the vitamin diets. Stocking density and dietary treatments were found to significantly affect bone development, with the vitamin diet significantly increasing metatarsal length and femoral bone strength in broilers from high-density stocking density at 28 d of age. High stocking density increased the proportion of leg muscles and meat yield per square meter. In general, 25-(OH)D3 and additional vitamin E suppressed oxidative stress and ameliorated the negative effects of high-density stocking on bone development in a commercial chicken farm setting. Vitamin diets improved the FCR of broilers, while high-density stocking resulted in better economic outcomes.


High-density stocking is often associated with animal welfare risks in broilers, mainly in terms of oxidative stress and bone development. Nevertheless, farming at too low a density remains for the most part economically unviable. Modulation of antioxidant capacity and bone development by nutritional strategies in high-density-farmed broilers has proven an effective tool in developing countries. Therefore, the present study investigated the effects of applying diets with a higher biological potency of vitamin D3 25-hydroxycholecalciferol [25-(OH)D3] and a higher concentration of vitamin E on broiler production performance, antioxidant capacity and meat production performance at different densities of stocking under commercial farming conditions. The results indicated that the vitamin dietary treatments suppressed oxidative stress and ameliorated the negative effects of high-density farming on bone development.


Assuntos
Calcifediol , Galinhas , Animais , Calcifediol/farmacologia , Galinhas/fisiologia , Antioxidantes , Vitamina E/farmacologia , Dieta/veterinária , Suplementos Nutricionais , Vitaminas/farmacologia , Colecalciferol , Desenvolvimento Ósseo , Ração Animal/análise
18.
Syst Biol Reprod Med ; 69(6): 450-464, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37962399

RESUMO

The most prevalent endocrine and metabolic condition in women of reproductive age are polycystic ovary syndrome (PCOS) with significant risk factors such as circadian rhythm and melatonin disruption. The aim of this study is to assess the effect of vitamin E in combination with a combined oral contraceptive (COC) on continuous light-induced PCOS using hormonal measures, oxidative stress (OS) indicators, and the inhibin beta-A (INHBA) gene, which targets the melatonin protein kinase C (PKC) pathway. An in silico technique anticipated INHBA's binding affinity for vitamin E and COC. For the in vivo investigation (IAEC/240/2021), female SD rats were divided into six groups and subjected to a 16-week induction period, followed by a 2-month test drug treatment with drospirenone (DRSP) as a standard. Serum testosterone, FSH, melatonin, and OS were calculated as hormonal markers. The expression of the INHBA gene was studied to see if it could be linked to the circadian rhythm and OS via the melatonin PKC pathway. According to the in silico study, vitamin E and DRSP had higher binding energy for the INHBA (-8.6 kcal/mol and -8.4 kcal/mol, respectively). When compared to the control group, in vivo results showed a substantial decrease in testosterone levels (p = .05), as well as changes in FSH (p = .78) and melatonin (p = .13). IHNBA gene expression has also dramatically increased, stimulating FSH production in the pituitary gland. Vitamin E and COC concomitantly are beneficial against PCOS because it modulates OS, which in turn influences circadian rhythm and the melatonin PKC pathway.


Assuntos
Melatonina , Síndrome do Ovário Policístico , Feminino , Humanos , Animais , Ratos , Anticoncepcionais Orais Combinados/farmacologia , Anticoncepcionais Orais Combinados/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Melatonina/farmacologia , Vitamina E/farmacologia , Vitamina E/uso terapêutico , Ratos Sprague-Dawley , Hormônio Foliculoestimulante , Testosterona
19.
Anim Reprod Sci ; 259: 107378, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37989002

RESUMO

Oxidative status is important in reproductive performance and using two natural antioxidants is more beneficial than one in nulliparous rabbits. The goal, effect of vitamin E (VitE), D-limonene (DL), and VitE+DL on maternal LBW (MLBW), conception (CR), pregnancy (PR), and kindling rates (KR), gestation length (GL), total litter size at birth (TLSB) and weaning (TLSW), live kits at birth (LKB) and weaning (LKW), dead kits at birth (DKB) and weaning (DKW), kits mortality rate at weaning (KMRW), Kit weight at birth (KWB) and weaning (KWW), total kit weight at birth (TKWB) and weaning (TKWW), and concentrations of progesterone (P4) and Malondialdehyde (MDA), during first two pregnancies. A total of 24 healthy female WNZ rabbits were randomly selected and assigned into four groups (6/each). Control (animals injected with 1.0 mL propylene glycol), VitE (60 mg IM injection/animal, 2X/week pre-mating and 3X post-mating until mid-pregnancy, DL (20 mg IM injection/animal, 2X/week pre-mating and 1X at mating, and VitE+DL (IM injection/animal with the same doses and times applied in VitE and DL groups. All animals were treated during 1st pregnancy only. The results confirmed that animals treated with VitE+DL gained significant maternal LBW in 1st pregnancy, reduced dead kit number at birth and kit mortality rate at weaning, increased live kits and total kit weight at birth and weaning in the two pregnancies, and also increased significantly kit weight at birth and weaning in the treatments than controls in the two pregnancies, and DL was greater in 1st pregnancy. Progesterone concentrations in mid-pregnancy rose significantly in VitE+DL during 1st pregnancy and DL in 2nd pregnancy. Malondialdehyde concentrations dropped significantly in VitE and VitE+DL in mid-pregnancy in the two pregnancies. Eventually, the integration of VitE and DL displayed their unique properties for improving productive and reproductive performance in nulliparous rabbits.


Assuntos
Limoneno , Vitamina E , Animais , Feminino , Gravidez , Coelhos , Peso ao Nascer , Limoneno/farmacologia , Tamanho da Ninhada de Vivíparos , Malondialdeído , Progesterona , Reprodução , Vitamina E/farmacologia , Desmame
20.
Ecotoxicol Environ Saf ; 268: 115675, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37984288

RESUMO

Di-(2-ethylhexyl)-phthalate (DEHP), a common Phthalic acid ester (PAEs), has been reported to be associated with diabetes mellitus, yet the underlying mechanisms remain unknown. Combined nutrient interventions have been shown to alleviate the diabetic toxicity of DEHP. However, the effects and mechanisms of the combined intervention of Astragalus and vitamins (C and E) are currently unknown. In this study, we investigated the potential mechanisms of DEHP-induced diabetes mellitus through transcriptome analysis and vitro experiments using rat insulinoma cells (INS-1 cells). Furthermore, we explored the protection of the combined Astragalus, vitamin C, and vitamin E on DEHP-induced diabetes mellitus through these mechanisms. INS-1 cells in the logarithmic growth period were exposed to 125 umol/L DEHP followed by high-throughput sequencing analysis. The cell proliferation inhibition rate was determined using MTT assay for each group, and the cell apoptosis rate and intracellular ROS level were measured using flow cytometer. Finally, insulin levels and markers of oxidative stress were detected using ELISA kits in different groups. A total of 372 differentially expressed genes were found between the 125 umol/L DEHP and control groups, subsequent functional enrichment analyses indicated that DEHP induced oxidative stress and disturbed insulin levels. In INS-1 cells, the rate of cell proliferation inhibition, apoptosis, and the degree of oxidative stress increased concentration-dependently with increasing DEHP concentrations, while antioxidant intervention could reverse these changes. Insulin synthesis and secretion decreased after 240 µmol/L DEHP exposure stimulated by 25 mM glucose in INS-1 cells, also could antioxidant intervention alleviate these reductions. Based on these results, the underlying mechanism of DEHP impairing the function of INS-1 cells might be through apoptosis pathways induced by oxidative stress and direct reduction of insulin levels (both synthesis and secretion), while the optimal combination of Astragalus and vitamins (C and E) could exert an alleviating effect.


Assuntos
Diabetes Mellitus , Dietilexilftalato , Insulinoma , Neoplasias Pancreáticas , Ratos , Animais , Vitamina E/farmacologia , Ácido Ascórbico/farmacologia , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Insulina/metabolismo , Dietilexilftalato/toxicidade , Estresse Oxidativo , Vitaminas/farmacologia
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