Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 12.925
Filtrar
1.
Nutrients ; 16(17)2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39275153

RESUMO

Aging is the result of the accumulation of a wide variety of molecular and cellular damages over time, meaning that "the more damage we accumulate, the higher the possibility to develop age-related diseases". Therefore, to reduce the incidence of such diseases and improve human health, it becomes important to find ways to combat such damage. In this sense, geroprotectors have been suggested as molecules that could slow down or prevent age-related diseases. On the other hand, nutraceuticals are another set of compounds that align with the need to prevent diseases and promote health since they are biologically active molecules (occurring naturally in food) that, apart from having a nutritional role, have preventive properties, such as antioxidant, anti-inflammatory and antitumoral, just to mention a few. Therefore, in the present review using the specialized databases Scopus and PubMed we collected information from articles published from 2010 to 2023 in order to describe the role of nutraceuticals during the aging process and, given their role in targeting the hallmarks of aging, we suggest that they are potential geroprotectors that could be consumed as part of our regular diet or administered additionally as nutritional supplements.


Assuntos
Envelhecimento , Suplementos Nutricionais , Humanos , Envelhecimento/efeitos dos fármacos , Antioxidantes/farmacologia , Substâncias Protetoras/farmacologia , Animais
2.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(8): 1571-1581, 2024 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-39276053

RESUMO

OBJECTIVE: To explore the mechanism underlying the protective effect of Lonicerae japonicae flos (LJF) extract against doxorubicin (DOX) -induced liver injury in mice. METHODS: Network pharmacology methods were used to obtain the intersection genes between LJF targets and disease targets, based on which the protein-protein interaction (PPI) network was constructed using STRING database for screening the core targets using Cytoscape software. DAVID database was used for bioinformatics analysis, and the core components and core targets were verified using molecular docking study. In a mouse model of DOX-induced liver injury, the effect of LJF extract on liver pathologies, serum levels of ALT and AST, and hepatic expressions of HYP, ROS, TNF-α, IL-6, COL-Ⅳ and P53 proteins were evaluated using HE and Masson staining, ELISA, and Western blotting. RESULTS: We identified 12 core targets from 43 intersection genes involving cancer pathway, IL-17 signaling pathway, and TNF signaling pathways. Molecular docking study suggested that 10 core components of LJF could bind to different core targets. The mice with DOX-induced liver injury showed elevated serum AST and ALT levels with obvious liver injury and fibrosis, increased ROS content, and enhanced expressions of TNF-α, IL-6, HYP, COL-Ⅳ and P53 proteins in the liver tissue. All these changes in the mouse models were significantly alleviated by treatment with LJF extract, suggesting obviously lowered levels of oxidative stress, inflammation and fibrosis in the liver tissues. CONCLUSION: LJF extract is capable of alleviating DOX-induced liver injury in mice by downregulating Trp53, TNF and IL-6 to reduce liver oxidative stress, inflammation and fibrosis.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Doxorrubicina , Interleucina-6 , Lonicera , Simulação de Acoplamento Molecular , Fator de Necrose Tumoral alfa , Animais , Doxorrubicina/efeitos adversos , Camundongos , Lonicera/química , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Extratos Vegetais/farmacologia , Fígado/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Proteína Supressora de Tumor p53/metabolismo , Substâncias Protetoras/farmacologia , Mapas de Interação de Proteínas , Transdução de Sinais/efeitos dos fármacos , Farmacologia em Rede
3.
Redox Rep ; 29(1): 2395779, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39221774

RESUMO

OBJECTIVES: Alcohol and its metabolites, such as acetaldehyde, induced hepatic mitochondrial dysfunction play a pathological role in the development of alcohol-related liver disease (ALD). METHODS: In this study, we investigated the potential of nobiletin (NOB), a polymethoxylated flavone, to counter alcohol-induced mitochondrial dysfunction and liver injury. RESULTS: Our findings demonstrate that NOB administration markedly attenuated alcohol-induced hepatic steatosis, endoplasmic reticulum stress, inflammation, and tissue damage in mice. NOB reversed hepatic mitochondrial dysfunction and oxidative stress in both alcohol-fed mice and acetaldehyde-treated hepatocytes. Mechanistically, NOB restored the reduction of hepatic mitochondrial transcription factor A (TFAM) at both mRNA and protein levels. Notably, the protective effects of NOB against acetaldehyde-induced mitochondrial dysfunction and cell death were abolished in hepatocytes lacking Tfam. Furthermore, NOB administration reinstated the levels of hepatocellular NRF1, a key transcriptional regulator of TFAM, which were decreased by alcohol and acetaldehyde exposure. Consistent with these findings, hepatocyte-specific overexpression of Nrf1 protected against alcohol-induced hepatic Tfam reduction, mitochondrial dysfunction, oxidative stress, and liver injury. CONCLUSIONS: Our study elucidates the involvement of the NRF1-TFAM signaling pathway in the protective mechanism of NOB against chronic-plus-binge alcohol consumption-induced mitochondrial dysfunction and liver injury, suggesting NOB supplementation as a potential therapeutic strategy for ALD.


Assuntos
Flavonas , Transdução de Sinais , Animais , Camundongos , Flavonas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Masculino , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Estresse Oxidativo/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Fígado/efeitos dos fármacos , Fígado/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Etanol/toxicidade , Etanol/efeitos adversos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/tratamento farmacológico , Hepatopatias Alcoólicas/prevenção & controle , Hepatopatias Alcoólicas/patologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Fator 1 Nuclear Respiratório/metabolismo , Fator 1 Nuclear Respiratório/genética , Substâncias Protetoras/farmacologia , Fator 1 Relacionado a NF-E2/metabolismo , Fator 1 Relacionado a NF-E2/genética , Proteínas de Grupo de Alta Mobilidade
4.
Cell Mol Biol Lett ; 29(1): 119, 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39244559

RESUMO

BACKGROUND: Drug-induced liver injury (DILI) is gradually becoming a common global problem that causes acute liver failure, especially in acute hepatic damage caused by acetaminophen (APAP). Paeoniflorin (PF) has a wide range of therapeutic effects to alleviate a variety of hepatic diseases. However, the relationship between them is still poorly investigated in current studies. PURPOSE: This work aimed to explore the protective effects of PF on APAP-induced hepatic damage and researched the potential molecular mechanisms. METHODS: C57BL/6J male mice were injected with APAP to establish DILI model and were given PF for five consecutive days for treatment. Aiming to clarify the pharmacological effects, the molecular mechanisms of PF in APAP-induced DILI was elucidated by high-throughput and other techniques. RESULTS: The results demonstrated that serum levels of ALP, γ-GT, AST, TBIL, and ALT were decreased in APAP mice by the preventive effects of PF. Moreover, PF notably alleviated hepatic tissue inflammation and edema. Meanwhile, the results of TUNEL staining and related apoptotic factors coincided with the results of transcriptomics, suggesting that PF inhibited hepatocyte apoptosis by regulated MAPK signaling. Besides, PF also acted on reactive oxygen species (ROS) to regulate the oxidative stress for recovery the damaged mitochondria. More importantly, transmission electron microscopy showed the generation of autophagosomes after PF treatment, and PF was also downregulated mTOR and upregulated the expression of autophagy markers such as ATG5, ATG7, and BECN1 at the mRNA level and LC3, p62, ATG5, and ATG7 at the protein level, implying that the process by which PF exerted its effects was accompanied by the occurrence of autophagy. In addition, combinined with molecular dynamics simulations and western blotting of MAPK, the results suggested p38 as a direct target for PF on APAP. Specifically, PF-activated autophagy through the downregulation of MAPK/mTOR signaling, which in turn reduced APAP injury. CONCLUSIONS: Paeoniflorin mitigated liver injury by activating autophagy to suppress oxidative stress and apoptosis via the MAPK/mTOR signaling pathway. Taken together, our findings elucidate the role and mechanism of paeoniflorin in DILI, which is expected to provide a new therapeutic strategy for the development of paeoniflorin.


Assuntos
Acetaminofen , Autofagia , Doença Hepática Induzida por Substâncias e Drogas , Glucosídeos , Hepatócitos , Camundongos Endogâmicos C57BL , Monoterpenos , Serina-Treonina Quinases TOR , Animais , Autofagia/efeitos dos fármacos , Glucosídeos/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Monoterpenos/farmacologia , Masculino , Hepatócitos/metabolismo , Hepatócitos/efeitos dos fármacos , Camundongos , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Acetaminofen/efeitos adversos , Transdução de Sinais/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo/efeitos dos fármacos
5.
BMC Complement Med Ther ; 24(1): 329, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39232773

RESUMO

BACKGROUND: Breast cancer is one of the most common diseases globally that may have side effects on liver and renal function. Pharmacological treatments to reduce adverse liver and renal effects are still limited. It has been proposed that silymarin may possess hepatoprotective and anti-inflammatory properties. The present trial aims to assess the hepatorenal protective efficacy of silymarin supplementation in cancer patients receiving chemotherapy in an outpatient setting. METHOD: This is a randomized, placebo-controlled clinical trial that recruited female breast cancer patients. Participants were randomly assigned to one placebo group and two intervention groups. The control group received 140 mg of placebo daily, while the two intervention groups received 140 mg silymarin daily. Follow-up assessments were conducted at baseline, 3 weeks, and 6 weeks. At the beginning of the study, the patients were subjected to a computed tomography (CT) scan, and the liver and renal parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), bilirubin, Blood urea nitrogen (BUN) and Creatinine (Cr) were examined through laboratory tests. RESULTS: Despite two deaths and three dropouts, 100 patients completed the study. Silymarin showed significant effects on liver enzymes in the levels of ALP and bilirubin (P < 0.05), with no significant impact on renal function in the levels of Blood urea nitrogen (BUN) and Creatinine (Cr) (P > 0.05). The medication was well-tolerated, with minimal reported side effects (P > 0.05). DISCUSSION: The study suggests that silymarin may have hepato-renal protective potential in breast cancer patients and improve patient tolerance to chemotherapy. The data presented on the efficacy and safety of silymarin may provide stronger foundation for further trials and for a possible use in clinical practice. TRIAL REGISTRATION INFORMATION: Registration Number: IRCT20201123049474N2, First Trial Registration: 16/08/2021, Access: https://www.irct.behdasht.gov.ir/trial/57641.


Assuntos
Neoplasias da Mama , Silimarina , Humanos , Silimarina/farmacologia , Silimarina/uso terapêutico , Feminino , Pessoa de Meia-Idade , Neoplasias da Mama/tratamento farmacológico , Adulto , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Idoso , Fígado/efeitos dos fármacos
6.
Food Funct ; 15(18): 9298-9314, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39163024

RESUMO

High Fischer ratio oligopeptides derived from Antarctic krill (HFOPs-AK) were screened, and their hepatoprotective effects and potential mechanisms were investigated. Herein, HFOPs-AK, with a Fischer ratio of 29 g/g (40.22 mol/mol) (MW < 1000 Da), were prepared via two-step enzymatic hydrolysis using chymotrypsin and flavourzyme and aromatic amino acid removal. Seventy-eight characteristic peptides were identified from HFOPs-AK through UHPLC-Q/TOF, with peptides containing Leu, Val, or Ile accounting for 79%. High hepatoprotective peptides were purified using GFC and RP-HPLC and identified as SDELGW and LLGWDDM. Furthermore, a murine model of acute liver injury induced by alcohol was successfully established. It was demonstrated that the oral administration of HFOPs-AK (800 mg per kg bw per d) remarkably increased the contents of ADH and ALDH compared with the model group, reaching 3.40 and 5.10 U mg-1 prot, respectively. Further, it was revealed that HFOPs-AK could effectively mitigate hepatic oxidative stress by increasing the levels of GSH-Px (p < 0.01) and decreasing the level of MDA (p < 0.05). Additionally, HFOPs-AK (800 mg per kg bw per d) attenuated liver inflammation by down-regulating the mRNA levels of TNF-α, IL-1ß, and IL-6 by 40.45%, 38.48%, and 35.83%, respectively. Therefore, HFOPs-AK may have the potential as a new nutritional supplement for the treatment of alcoholic liver injury.


Assuntos
Euphausiacea , Fígado , Oligopeptídeos , Estresse Oxidativo , Animais , Euphausiacea/química , Camundongos , Oligopeptídeos/farmacologia , Oligopeptídeos/química , Masculino , Fígado/efeitos dos fármacos , Fígado/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Hepatopatias Alcoólicas/tratamento farmacológico , Hepatopatias Alcoólicas/prevenção & controle , Substâncias Protetoras/farmacologia , Substâncias Protetoras/química , Regiões Antárticas
7.
Bioorg Chem ; 152: 107732, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39178702

RESUMO

Phytochemical analysis of the peeled stems of Syringa pinnatifolia Hemsl. led to the discovery of 13 undescribed lignans, namely helanols A and B (1 and 2) and alashanenols W-G1 (3-13), as well as four known analogues, of which helanols A and B were lignans with novel skeleton of α-ß' linkage. The structures were unambiguously established by extensive spectroscopic analyses, NMR calculations, ECD calculations, and single crystal X-ray crystallography. Five lignans (1, 2, 5, 11 and 13) exhibited a moderate protective effect against H2O2-induced oxidative injuries in H9c2 cells with the protective rates of 11.3-20.6 % at the concentration of 0.3-20 µM, while the positive control quercetin showed protective rates of 58.7 % at 10 µM. Further mechanism investigation suggested that 1 and 2 exerted the protective effect by regulating the expression of Nrf2/HO-1.


Assuntos
Peróxido de Hidrogênio , Lignanas , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Syringa , Lignanas/farmacologia , Lignanas/química , Lignanas/isolamento & purificação , Fator 2 Relacionado a NF-E2/metabolismo , Peróxido de Hidrogênio/farmacologia , Peróxido de Hidrogênio/antagonistas & inibidores , Estresse Oxidativo/efeitos dos fármacos , Syringa/química , Estrutura Molecular , Ratos , Relação Estrutura-Atividade , Animais , Relação Dose-Resposta a Droga , Heme Oxigenase-1/metabolismo , Substâncias Protetoras/farmacologia , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificação , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos
8.
Fish Shellfish Immunol ; 153: 109824, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39127393

RESUMO

Plantago asiatica seeds (PS) are commonly used as a medicinal plant. This study investigates the efficacy of PS against heavy metal toxicity in white shrimp (Penaeus vannamei). After feeding PS diet (5 g/kg) or basal diet (control group) for 7 days, shrimps were exposed to sublethal concentrations of heavy metals in seawater (As: 12 mg/L, Pb: 250 mg/L, Hg: 0.4 mg/L). The 7-day survival observation showed that the survival in groups fed with PS were significantly higher than that in the control group, revealing that dietary PS had the efficacy to mitigate heavy metal toxicity in white shrimp. Under the same feeding condition, white shrimps were exposed to safety dose of heavy metals (1/10 of sublethal concentrations) to understand the mechanism of mitigation. The metal accumulations in haemolymph, gills, hepatopancreas, and muscle tissues as well as the immune, anti-oxidative, stress related gene expressions in haemocytes, gills and hepatopancreas were measured for 14 days. The As accumulation in gills and hepatopancreas of groups fed with PS were significantly lower than those of control group on day 7 and 14, respectively; The Pb concentration in haemolymph of group fed with PS was significantly lower than that of control group on day 7 and 14; The Hg concentration in hepatopancreas of the group fed with PS was significantly lower than that of control group on day 7. Dietary PS could mitigate heavy metal-induced immune suppression, oxidative stress, and stress response by positively regulating immune (proPO I, Toll, IMD), antioxidant (SOD, GST, Trx), and negatively regulating stress response genes (HSP70, MT). The present study demonstrated that dietary PS could protect white shrimp against metal toxicity by reducing metal accumulations and regulating the immune, antioxidant, and stress response gene expressions in specific tissue. Therefore, PS may serve as a beneficial feed additive in the aquaculture.


Assuntos
Ração Animal , Dieta , Penaeidae , Plantago , Sementes , Poluentes Químicos da Água , Animais , Penaeidae/imunologia , Penaeidae/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Sementes/química , Ração Animal/análise , Dieta/veterinária , Plantago/química , Metais Pesados/toxicidade , Suplementos Nutricionais/análise , Substâncias Protetoras/farmacologia , Substâncias Protetoras/administração & dosagem , Arsênio/toxicidade , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Brânquias/imunologia
9.
Plant Physiol Biochem ; 215: 109059, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39178802

RESUMO

Industrialization-driven surface ozone (O3) pollution significantly impairs plant growth. This study evaluates the effectiveness of exogenous protectants [3 mg L⁻1 abscisic acid (ABA), 400 mg L⁻1 ethylenediurea (EDU), and 80 mg L⁻1 spermidine (Spd)] on Trifolium repens subjected to O3 stress in open-top chambers, focusing on plant growth and dynamics of culturable endophytic fungal communities. Results indicate that O3 exposure adversely affects photosynthesis, reducing root biomass and altering root structure, which further impacts the ability of plant to absorb essential nutrients such as potassium (K), magnesium (Mg), and zinc (Zn). Conversely, the application of ABA, EDU, and Spd significantly enhanced total biomass and chlorophyll content in T. repens. Specifically, ABA and Spd significantly improved root length, root surface area, and root volume, while EDU effectively reduced leaves' malondialdehyde levels, indicating decreased oxidative stress. Moreover, ABA and Spd treatments significantly increased leaf endophytic fungal diversity, while root fungal abundance declined. The relative abundance of Alternaria in leaves was substantially reduced by these treatments, which correlated with enhanced chlorophyll content and photosynthesis. Concurrently, EDU and Spd treatments increased the abundance of Plectosphaerella, enhance the absorption of K, Ca, and Mg. In roots, ABA treatment increased the abundance of Paecilomyces, while Spd treatment enhanced the presence of Stemphylium, linked to improved nitrogen (N), phosphorus (P), and K uptake. These findings suggest that specific symbiotic fungi mitigate O3-induced stress by enhancing nutrient absorption, promoting growth. This study highlights the potential of exogenous protectants to enhance plant resilience against O3 pollution through modulating interactions with endophytic fungal communities.


Assuntos
Ozônio , Trifolium , Trifolium/microbiologia , Trifolium/efeitos dos fármacos , Trifolium/crescimento & desenvolvimento , Ozônio/farmacologia , Endófitos/efeitos dos fármacos , Endófitos/fisiologia , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/microbiologia , Folhas de Planta/metabolismo , Raízes de Plantas/microbiologia , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Ácido Abscísico/metabolismo , Ácido Abscísico/farmacologia , Clorofila/metabolismo , Fotossíntese/efeitos dos fármacos , Fungos/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Biomassa , Compostos de Fenilureia
10.
Part Fibre Toxicol ; 21(1): 30, 2024 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-39118174

RESUMO

Plastic pollution is an emerging environmental issue, with microplastics and nanoplastics raising health concerns due to bioaccumulation. This work explored the impact of polystyrene nanoparticle (PS-NPs) exposure during prepuberty on male reproductive function post maturation in rats. Rats were gavaged with PS-NPs (80 nm) at 0, 3, 6, 12 mg/kg/day from postnatal day 21 to 95. PS-NPs accumulated in the testes and reduced sperm quality, serum reproductive hormones, and testicular coefficients. HE staining showed impaired spermatogenesis. PS-NPs disrupted the blood-testis barrier (BTB) by decreasing junction proteins, inducing inflammation and apoptosis. Transcriptomics identified differentially expressed genes related to metabolism, lysosome, apoptosis, and TLR4 signaling. Molecular docking revealed Cordycepin could compete with polystyrene for binding to TLR4. Cordycepin alleviated oxidative stress and improved barrier function in PS-NPs treated Sertoli cells. In conclusion, prepubertal PS-NPs exposure induces long-term reproductive toxicity in male rats, likely by disrupting spermatogenesis through oxidative stress and BTB damage. Cordycepin could potentially antagonize this effect by targeting TLR4 and warrants further study as a protective agent. This study elucidates the mechanisms underlying reproductive toxicity of PS-NPs and explores therapeutic strategies.


Assuntos
Barreira Hematotesticular , Desoxiadenosinas , Nanopartículas , Poliestirenos , Espermatogênese , Testículo , Animais , Masculino , Desoxiadenosinas/farmacologia , Barreira Hematotesticular/efeitos dos fármacos , Poliestirenos/toxicidade , Nanopartículas/toxicidade , Espermatogênese/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/metabolismo , Simulação de Acoplamento Molecular , Microplásticos/toxicidade , Receptor 4 Toll-Like/metabolismo , Apoptose/efeitos dos fármacos , Maturidade Sexual/efeitos dos fármacos , Substâncias Protetoras/farmacologia
11.
Cell Mol Biol (Noisy-le-grand) ; 70(7): 180-185, 2024 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-39097876

RESUMO

Here, the protective effect of antioxidant Idebenone (IDB) on renovascular hypertension was studied. The two-kidney one-clip (2K-1C) model of renal hypertension was established. The rats were divided into 3 groups: sham-operation group, 2K-1C renal hypertensive rats' model group and model treated with IDB group. The mean arterial blood pressure (MBP) of rats was measured and pathological condition of kidney was observed by H&E staining. The change of renal damage biomarkers (Cre, BUN, urine proteins), inflammatory factors (IL-6, IL-1ß and TNF-α), oxidative stress ratio and key factors (MDA, SOD and CAT) were assessed by kits. The apoptosis key proteins (BAD, BAX, Caspase9, GSK-3ß) were detected via Western blot. The 2K-1C model of renal hypertension was established. IDB reduced the MBP, Cre, BUN, urine proteins and improved the pathological condition of 2K-1C kidney. IDB restrained the inflammation factors (IL-6, IL-1ß and TNF-α) and oxidative stress in kidney of renal hypertensive rats' model. Besides, IDB suppressed the expression of apoptosis key factors (BAD, BAX, Caspase9, GSK-3ß) in kidney of renal hypertensive rats' model. IDB protects the kidneys of rats with renovascular arterial hypertension by inhibiting inflammation, oxidative stress, and apoptosis. These findings might provide medication guidance for IDB in renovascular arterial hypertension.


Assuntos
Apoptose , Hipertensão Renovascular , Rim , Estresse Oxidativo , Ubiquinona , Animais , Estresse Oxidativo/efeitos dos fármacos , Hipertensão Renovascular/tratamento farmacológico , Hipertensão Renovascular/metabolismo , Apoptose/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Masculino , Ubiquinona/análogos & derivados , Ubiquinona/farmacologia , Ubiquinona/uso terapêutico , Ratos , Ratos Sprague-Dawley , Pressão Sanguínea/efeitos dos fármacos , Antioxidantes/farmacologia , Modelos Animais de Doenças , Substâncias Protetoras/farmacologia
12.
BMC Pharmacol Toxicol ; 25(1): 50, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39138519

RESUMO

This study reports a novel, eco-friendly; fast and cost-effective microwave method for synthesizing carboxymethylated graphene oxide (CMGO) from sugarcane residues. Fourier-transform infrared spectroscopy (FTIR) confirmed successful CMGO synthesis through the presence of characteristic peaks at 1567.93 and 1639.29 cm-1 (COONa vibrations) and increased CH2 intensity compared to unmodified graphene oxide (GO). Furthermore, CMGO derived from sugarcane residues demonstrated potential in mitigating the side effects of toxic materials like carbon tetrachloride (CCl4). Treatment with CMGO partially reduced elevated levels of liver enzymes (ALT and AST) and nitrogenous waste products (urea and uric acid) in CCl4-induced liver damage models, suggesting an improvement in liver function despite ongoing cellular damage.This work paves the way for a sustainable and economical approach to produce functionalized graphene oxide with promising biomedical applications in alleviating toxin-induced liver injury.


Assuntos
Tetracloreto de Carbono , Doença Hepática Induzida por Substâncias e Drogas , Grafite , Fígado , Micro-Ondas , Grafite/química , Animais , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/metabolismo , Tetracloreto de Carbono/toxicidade , Masculino , Substâncias Protetoras/farmacologia , Substâncias Protetoras/química , Substâncias Protetoras/uso terapêutico , Ácido Úrico , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Ureia/análogos & derivados , Ureia/farmacologia , Camundongos
13.
Braz J Biol ; 84: e279117, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39140499

RESUMO

Cisplatin is an antineoplastic medicine used in the treatment for various types of cancer. Among its side effects is ototoxicity, which may result in a bilateral and irreversible hearing loss. The ototoxic effect in the pediatric population has a bigger impact as it compromises language acquisition. The discovery of drugs with otoprotective effects and the optimal way to administer them have become significant challenges in minimizing the impact of cisplatin regarding auditory function. The objective was to understand otoprotective drugs and their relevance in the preventive treatment to cisplatin-induced ototoxicity in childhood. An integrative review was conducted by consulting databases including PubMed, Bireme, MedLine, LILACS, SciELO, and ClinicalTrials.gov. The search strategy was performed by crossing descriptors (DeCS and MeSH) and free terms. Studies published in English, Spanish, and Portuguese were selected, with no publication year restrictions. Subsequently, articles were selected according to inclusion and exclusion criteria. A total of 736 articles were found in PubMed, 431 in Bireme, 425 in MedLine, 6 in LILACS, 0 in SciELO, and 4 in ClinicalTrials.gov. After document analysis, 12 articles were selected for full analysis. Evidence was found for 8 substances with potential otoprotective effects when used with cisplatin, which tend to minimize the impact of cisplatin regarding auditory function. The substances found were: Amifostine, Dexamethasone, Genistein, Ginkgo Biloba, Lycopene, N-acetylcysteine, Polydatin also Sodium Thiosulfate. In general, these drugs are applied before, during, or after cisplatin infusion, depending on the chosen drug, via intravenous, oral, or transtympanic injections, acting as antioxidant therapy. The biochemical effects of these substances are relevant to their potential otoprotective properties, including the inactivation of oxygen free radicals and electrophilic platinum species. The use of these substances can reduce ototoxicity, decreasing cisplatin-induced hearing loss and improving the confort of life, especially for children.


Assuntos
Antineoplásicos , Cisplatino , Ototoxicidade , Cisplatino/efeitos adversos , Humanos , Ototoxicidade/prevenção & controle , Ototoxicidade/etiologia , Criança , Antineoplásicos/efeitos adversos , Substâncias Protetoras , Perda Auditiva/prevenção & controle , Perda Auditiva/induzido quimicamente
14.
Curr Drug Discov Technol ; 21(4): e191223224660, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39206705

RESUMO

Numerous factors, including exposure to harmful substances, drinking too much alcohol, contracting certain hepatitis serotypes, and using specific medicines, contribute to the development of liver illnesses. Lipid peroxidation and other forms of oxidative stress are the main mechanisms by which hepatotoxic substances harm liver cells. Pathological changes in the liver include a rise in the levels of blood serum, a decrease in antioxidant enzymes, as well as the formation of free radical radicals. It is necessary to find pharmaceutical alternatives to treat liver diseases to increase their efficacy and decrease their toxicity. For the development of new therapeutic medications, a greater knowledge of primary mechanisms is required. In order to mimic human liver diseases, animal models are developed. Animal models have been used for several decades to study the pathogenesis of liver disorders and related toxicities. For many years, animal models have been utilized to investigate the pathophysiology of liver illness and associated toxicity. The animal models are created to imitate human hepatic disorders. This review enlisted numerous hepatic damage in vitro and in vivo models using various toxicants, their probable biochemical pathways and numerous metabolic pathways via oxidative stressors, different serum biomarkers enzymes are discussed, which will help to identify the most accurate and suitable model to test any plant preparations to check and evaluate their hepatoprotective properties.


Assuntos
Modelos Animais de Doenças , Estresse Oxidativo , Animais , Humanos , Estresse Oxidativo/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico , Hepatopatias/tratamento farmacológico , Hepatopatias/metabolismo , Hepatopatias/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia
15.
Int J Mol Sci ; 25(16)2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39201451

RESUMO

Fumonisin B1 (FB1), a mycotoxin produced by Fusarium species, is prevalent in crops and animal feed, posing significant health risks to livestock and humans. FB1 induces oxidative stress in Sertoli cells, destroys testicular structure, and affects spermatogenesis. However, methods to mitigate the reproductive toxicity of FB1 in testes remain unknown. Quercetin, a natural flavonoid antioxidant, may offer protective benefits. This study investigated the protective effects and mechanisms of quercetin against FB1-induced reproductive toxicity in TM4 cells (a Sertoli cell line). The results indicated that 40 µM quercetin improved cell viability, reduced apoptosis, and preserved cell functions. Quercetin also decreased reactive oxygen species (ROS) levels in TM4 cells exposed to FB1, enhanced the expression of antioxidant genes, and improved mitochondrial membrane potential. Compared with FB1 alone, the combination of quercetin and FB1 increased ATP levels, as well as pyruvate and lactic acid, the key glycolysis products. Furthermore, this combination elevated the mRNA and protein expression of glycolysis-related genes, including glucose-6-phosphate isomerase 1 (Gpi1), hexokinase 2 (Hk2), aldolase (Aldoa), pyruvate kinase, muscle (Pkm), lactate dehydrogenase A (Ldha) and phosphofructokinase, liver, B-type (Pfkl). Quercetin also boosted the activity of PKM and LDHA, two crucial glycolytic enzymes. In summary, quercetin mitigates FB1-induced toxicity in TM4 cells by reducing ROS levels and enhancing glycolysis. This study offers new insights into preventing and treating FB1-induced toxic damage to the male reproductive system and highlights the potential application of quercetin.


Assuntos
Sobrevivência Celular , Fumonisinas , Quercetina , Espécies Reativas de Oxigênio , Células de Sertoli , Quercetina/farmacologia , Fumonisinas/toxicidade , Masculino , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Substâncias Protetoras/farmacologia
16.
Mol Med Rep ; 30(4)2024 10.
Artigo em Inglês | MEDLINE | ID: mdl-39092554

RESUMO

Alcohol­related liver disease (ALD) is a major health concern worldwide. In recent years, there has been growing interest in natural products and functional foods for preventing and treating ALD due to their potential antioxidant and hepatoprotective properties. Rosa roxburghii Tratt, known for its rich content of bioactive compounds, has demonstrated promising health benefits, including anti­inflammatory and antioxidant effects. Fermentation has been utilized as a strategy to enhance the bioavailability and efficacy of natural products. In the present study, using a mixture of Rosa roxburghii Tratt juice, lotus leaf extract and grape seed proanthocyanidins fermented by Lactobacillus plantarum HH­LP56, a novel fermented Rosa roxburghii Tratt (FRRT) juice was discovered that can prevent and regulate ethanol­induced liver cell damage. Following fermentation, the pH was significantly decreased, and the content of VC and superoxide dismutase (SOD) were significantly increased, along with a noticeable enhancement in hydroxyl and 2,2­diphenyl­1­picrylhydrazyl free radical scavenging abilities. Alpha Mouse liver 12 cells were exposed to ethanol for 24 h to establish an in vitro liver cell injury model. The present study evaluated the effects of FRRT on cell damage, lipid accumulation and oxidative stress markers. The results revealed that FRRT pretreatment (cells were pre­treated with 2.5 and 5 mg/ml FRRT for 2 h) significantly reduced lipid accumulation and oxidative stress in liver cells. Mechanistically, FRRT regulated lipid metabolism by influencing key genes and proteins, such as AMP­activated protein kinase, sterol regulatory element binding transcription factor 1 and Stearyl­CoA desaturase­1. Furthermore, FRRT enhanced antioxidant activity by increasing SOD activity, glutathione and catalase levels, while reducing reactive oxygen species and malondialdehyde levels. It also reversed the expression changes of ethanol­induced oxidative stress­related genes and proteins. In conclusion, a novel functional food ingredient may have been discovered with extensive potential applications. These findings indicated that FRRT has antioxidant properties and potential therapeutic benefits in addressing ethanol­induced liver cell damage through its effects on liver lipid metabolism and oxidative stress.


Assuntos
Proteínas Quinases Ativadas por AMP , Etanol , Fermentação , Hepatócitos , Fator 2 Relacionado a NF-E2 , Extratos Vegetais , Rosa , Transdução de Sinais , Animais , Camundongos , Rosa/química , Transdução de Sinais/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Proteínas Quinases Ativadas por AMP/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Linhagem Celular , Antioxidantes/farmacologia , Sucos de Frutas e Vegetais , Substâncias Protetoras/farmacologia
17.
Tissue Cell ; 90: 102509, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39098258

RESUMO

Heat stress from varicocele can heighten oxidative stress in the testes, impacting sperm function and male fertility. Antioxidant therapy is explored as a remedy for varicocele, while dietary factors like processed foods, sugar, and saturated fats correlate with male infertility. Advanced glycation end products (AGEs), generated through glycation processes, can provoke oxidative stress, inflammation, and adverse health consequences. Alpha-lipoic acid (ALA), a versatile antioxidant, may alleviate oxidative stress and counteract the impact of AGEs, potentially by enhancing glucose reabsorption. Alagebrium chloride (ALT711), an anti-AGE compound, exhibits promise in cardiovascular disease by disrupting AGE cross-links. This study investigates the effects of ALA and ALT-711 on testicular function in varicocele and AGEs animal models. Both AGE and varicocele were found to alter the natural trends, leading to abnormal patterns in sperm parameters, testicular functional tests, as well as the expression of CML, RAGE, and TNF-α proteins. However, the administration of ALA or ALT711 helped mitigate these effects. While ALA demonstrated a slightly greater overall benefit compared to ALT, the difference was not statistically significant.


Assuntos
Produtos Finais de Glicação Avançada , Testículo , Ácido Tióctico , Varicocele , Masculino , Animais , Ácido Tióctico/farmacologia , Produtos Finais de Glicação Avançada/metabolismo , Testículo/metabolismo , Testículo/efeitos dos fármacos , Testículo/patologia , Ratos , Varicocele/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Antioxidantes/farmacologia , Dieta , Fator de Necrose Tumoral alfa/metabolismo , Modelos Animais de Doenças , Ratos Sprague-Dawley , Tiazóis
18.
Tissue Cell ; 90: 102519, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39141932

RESUMO

Ethanol is a well-known hepatotoxic agent and date fruits have been associated with their biological actions. In current study, we have investigated the hepatoprotective potential of DFE on ethanol-induced cellular damages in human hepatoma (HepG2) cells. The hepatoprotective potential was assessed by exposing the HepG2 cells to non-toxic concentrations (15, 30, and 60 µg/mL) of DFE for 24 h; then toxic concentration (500 µM) of ethanol. Our results demonstrated that pretreatment with DFE significantly prohibited ethanol-induced hepatotoxicity in HepG2 cells. We observed that DFE treatment increased cell viability, reduced LDH leakage, restored cellular morphology, and inhibited caspase-3 enzyme activity in a dose dependent way, induced by ethanol. Further DFE was also effective in restoring the LPO, GSH, and catalase levels towards normal altered by ethanol. Our results also revealed that ethanol-induced ROS generation was significantly inhibited by DFE. The ethanol-induced mRNA expression of apoptotic related genes (p53, caspase-3, caspase-7, Bax, and Bcl-2) were also normalized by pretreatment with DFE. The findings from this study indicated that DFE can significantly protect HepG2 cells against ethanol-induced hepatotoxicity. Our study also provides scientific validation for the traditional use of DFE, aiming to understand its hepatoprotective potential. Altogether, to the best of our knowledge, this is the first study demonstrated that ethanol-induced hepatotoxicity can be prohibited by the DFE. Thus, DFE has a potential application in nutraceuticals as a therapeutic agent to prevent liver diseases.


Assuntos
Apoptose , Etanol , Frutas , Neoplasias Hepáticas , Phoeniceae , Extratos Vegetais , Humanos , Células Hep G2 , Apoptose/efeitos dos fármacos , Etanol/toxicidade , Extratos Vegetais/farmacologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Phoeniceae/química , Frutas/química , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Substâncias Protetoras/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Caspase 3/metabolismo
19.
J Nutr Biochem ; 133: 109719, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39103108

RESUMO

This study investigated the protective effect of dulcitol on LPS-induced intestinal injury in piglets and explored the underlying molecular mechanisms. A total of 108 piglets were divided into three groups: CON, LPS, and DUL. The CON and LPS groups were fed a basal diet, the DUL group was fed a diet supplementation with 500 mg/kg dulcitol. On day 29, 6 piglets in the LPS and DUL groups were injected with 100 µg/kg BW of LPS. At 4 h postchallenge, all pigs were slaughtered, and colonic samples were collected. Results showed that dulcitol supplementation boosted intestinal barrier function in LPS-challenged piglets by enhancing intestinal morphology and integrity, and increasing the gene expression of zonula occludens-1, claudin-1, and occludin in the colonic mucosa (P <0.05). Metabolomics showed DUL supplementation mainly increased (P <0.05) the metabolites related to steroid and vitamin metabolism (Cholesterol and Vitamin C). Proteomics showed that dulcitol supplementation altered the protein expression involved in maintaining barrier integrity (FN1, CADM1, and PARD3), inhibiting inflammatory response (SLP1, SFN, and IRF3), and apoptosis (including FAS, ING1, BTK, MTHFR, NOX, and P53BP2) in LPS-challenged piglets (P <0.05). Additionally, dulcitol addition also suppressed the TLR4/NF-κB signaling pathway and apoptosis in mRNA and protein levels. Dulcitol increased the abundance of short-chain fatty acid-producing bacteria (Lactobacillus, Blautia, and Faecalibacterium) at the genus level, but decreased the relative abundance of Proteobacteria at the phylum level and Pseudomonas and Delftia at the genus level in piglets (P<.05). In conclusion, these results suggested that the addition of dulcitol alleviated LPS-induced intestinal barrier injury in piglets, probably by maintaining its integrity, inhibiting the TLR4/NF-κB signaling pathways and apoptosis, and modulating the gut microbiota. Therefore, dulcitol can be considered a potential dietary additive for improving intestinal health in pig models.


Assuntos
Suplementos Nutricionais , Mucosa Intestinal , Lipopolissacarídeos , Animais , Lipopolissacarídeos/toxicidade , Suínos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Enteropatias/induzido quimicamente , Enteropatias/prevenção & controle , Enteropatias/metabolismo , Intestinos/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Apoptose/efeitos dos fármacos , Masculino
20.
J Agric Food Chem ; 72(34): 18918-18929, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39140375

RESUMO

An effective method was developed for preparing galloylated procyanidins (GPCs) using galloyl-attached nucleophilic degradation. Under degradation conditions optimized through Box-Behnken design and single-factor experiments, two dimeric and three tetrameric GPCs were produced, with the yield of procyanidin B2-3'-O-gallate (B2-3'-G) reaching up to 232 mg/g (PPCs). The structure of B2-3'-G was identified by UV, FTIR, NMR, CD, MS, and phloroglucinolysis. Furthermore, the protective effect of B2-3'-G against alcohol-induced liver injury (ALI) was investigated. Compared with the parent compounds, B2-3'-G exhibited a stronger capacity for inhibiting ALI, attributed to its polymerization degree and galloyl group. Subsequent experiments revealed that the pretreatment of BRL-3A cells with B2-3'-G prior to ethanol improved ALI through activation of the Nrf2-HO-1/NQO1 pathway and initiation of enzymatic antioxidant systems. These findings suggest that GPC B2-3'-G is a potential hepatoprotective agent, which provides a new perspective for functional development of GPCs.


Assuntos
Biflavonoides , Catequina , Proantocianidinas , Substâncias Protetoras , Vitis , Proantocianidinas/química , Proantocianidinas/farmacologia , Biflavonoides/química , Biflavonoides/farmacologia , Catequina/química , Catequina/farmacologia , Catequina/análogos & derivados , Substâncias Protetoras/farmacologia , Substâncias Protetoras/química , Animais , Vitis/química , Ratos , Sementes/química , Humanos , Extrato de Sementes de Uva/química , Extrato de Sementes de Uva/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Linhagem Celular , Heme Oxigenase-1/metabolismo , Heme Oxigenase-1/genética , Polímeros/química , Polímeros/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA