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1.
Int J Nanomedicine ; 16: 2461-2475, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33814910

RESUMEN

Aim: To explore the effects of Radix Sophorae Flavescentis carbonisata-based carbon dots (RSFC-CDs) on an ethanol-induced acute gastric ulcer rat model. Methods: The structure, optical properties, functional groups and elemental composition of RSFC-CDs synthesized by one-step pyrolysis were characterized. The gastric protective effects of RSFC-CDs were evaluated and confirmed by applying a rat model of ethanol-induced acute gastric ulcers. The underlying mechanisms were investigated through the nuclear factor-kappa B (NF-κB) signalling pathway and oxidative stress. Results: RSFC-CDs with a diameter ranging from 2-3 nm mainly showed gastric protective effects by reducing the levels of NF-κB, tumour necrosis factor-α (TNF-α), interleukin (IL)-6, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione (GSH), malondialdehyde (MDA) and inducible nitric oxide synthase (iNOS) to inhibit ethanol-induced inflammation and oxidative stress. Conclusion: RSFC-CDs have anti-inflammatory and anti-oxidative effects, making them promising for application in ethanol-induced gastric injury.


Asunto(s)
Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Carbono/química , Medicamentos Herbarios Chinos/uso terapéutico , Sustancias Protectoras/uso terapéutico , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Enfermedad Aguda , Animales , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Regulación hacia Abajo/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Etanol/efectos adversos , Interleucina-6/metabolismo , Masculino , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Estrés Oxidativo/efectos de los fármacos , Espectroscopía de Fotoelectrones , Sustancias Protectoras/farmacología , Ratas Sprague-Dawley , Úlcera Gástrica/patología , Factor de Necrosis Tumoral alfa/metabolismo , Regulación hacia Arriba/efectos de los fármacos
2.
Int J Mol Sci ; 22(6)2021 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-33802882

RESUMEN

The curcumin degradation represents a significant limitation for its applications. The stability of free curcumin (FC) and immobilized curcumin in complex particles (ComPs) based on different polysaccharides was studied under the action of several factors. Ultraviolet-visible (UV-VIS) and Fourier-transform infrared (FTIR) spectroscopy proved the FC photodegradation and its role as a metal chelator: 82% of FC and between 26% and 39.79% of curcumin within the ComPs degraded after exposure for 28 days to natural light. The degradation half-life (t1/2) decreases for FC when the pH increases, from 6.8 h at pH = 3 to 2.1 h at pH = 9. For curcumin extracted from ComPs, t1/2 was constant (between 10 and 13 h) and depended on the sample's composition. The total phenol (TPC) and total flavonoids (TFC) content values increased by 16% and 13%, respectively, for FC exposed to ultraviolet light at λ = 365 nm (UVA), whereas no significant change was observed for immobilized curcumin. Antioxidant activity expressed by IC50 (µmoles/mL) for FC exposed to UVA decreased by 29%, but curcumin within ComPs was not affected by the UVA. The bovine serum albumin (BSA) adsorption efficiency on the ComPs surface depends on the pH value and the cross-linking degree. ComPs have a protective role for the immobilized curcumin.


Asunto(s)
Curcumina/farmacología , Polisacáridos/química , Sustancias Protectoras/farmacología , Adsorción , Animales , Antioxidantes/análisis , Compuestos de Bifenilo/química , Tampones (Química) , Bovinos , Curcumina/química , Curcumina/efectos de la radiación , Flavonoides/análisis , Depuradores de Radicales Libres/química , Concentración de Iones de Hidrógeno , Concentración 50 Inhibidora , Iones , Metales/química , Fenoles/análisis , Picratos/química , Albúmina Sérica Bovina/química , Soluciones , Espectroscopía Infrarroja por Transformada de Fourier , Rayos Ultravioleta
3.
Int J Mol Sci ; 22(6)2021 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-33799684

RESUMEN

Age-related hearing loss (ARHL), a sensorineural hearing loss of multifactorial origin, increases its prevalence in aging societies. Besides hearing aids and cochlear implants, there is no FDA approved efficient pharmacotherapy to either cure or prevent ARHL. We hypothesized that selegiline, an antiparkinsonian drug, could be a promising candidate for the treatment due to its complex neuroprotective, antioxidant, antiapoptotic, and dopaminergic neurotransmission enhancing effects. We monitored by repeated Auditory Brainstem Response (ABR) measurements the effect of chronic per os selegiline administration on the hearing function in BALB/c and DBA/2J mice, which strains exhibit moderate and rapid progressive high frequency hearing loss, respectively. The treatments were started at 1 month of age and lasted until almost a year and 5 months of age, respectively. In BALB/c mice, 4 mg/kg selegiline significantly mitigated the progression of ARHL at higher frequencies. Used in a wide dose range (0.15-45 mg/kg), selegiline had no effect in DBA/2J mice. Our results suggest that selegiline can partially preserve the hearing in certain forms of ARHL by alleviating its development. It might also be otoprotective in other mammals or humans.


Asunto(s)
Envejecimiento/fisiología , Modelos Animales de Enfermedad , Pérdida Auditiva Sensorineural/tratamiento farmacológico , Selegilina/farmacología , Administración Oral , Animales , Antiparkinsonianos/administración & dosificación , Antiparkinsonianos/farmacología , Umbral Auditivo/efectos de los fármacos , Umbral Auditivo/fisiología , Potenciales Evocados Auditivos del Tronco Encefálico/efectos de los fármacos , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , Pérdida Auditiva Sensorineural/fisiopatología , Humanos , Masculino , Ratones Endogámicos BALB C , Ratones Endogámicos DBA , Sustancias Protectoras/administración & dosificación , Sustancias Protectoras/farmacología , Selegilina/administración & dosificación , Transmisión Sináptica/efectos de los fármacos , Transmisión Sináptica/fisiología
4.
Ecotoxicol Environ Saf ; 214: 112078, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33676053

RESUMEN

It is well known that the dairy cow production is very sensitive to environmental factors, including high temperature, high humidity and radiant heat sources. High temperature-induced heat stress is the main environmental factor that causes oxidative stress and apoptosis, which affects the development of mammary glands in dairy cows. Dihydromyricetin (DMY) is a nature flavonoid compound extracted from Ampelopsis grossedentata; it has been shown to have various pharmacological functions, such as anti-inflammation, antitumor and liver protection. The present study aims to evaluate the protective effect of DMY on heat stress-induced dairy cow mammary epithelial cells (DCMECs) apoptosis and explore the potential mechanisms. The results show that heat stress triggers heat shock response and reduces cell viability in DCMECs; pretreatment of DCMECs with DMY (25 µM) for 12 h significantly alleviates the negative effects of heat stress on cells. DMY can provide cytoprotective effects by suppressing heat stress-caused mitochondrial membrane depolarization and mitochondrial dysfunction, Bax and Caspase 3 activity, and modulation of oxidative enzymes, thereby preventing ROS production and apoptosis in DCMECs. Importantly, DMY treatment could attenuate heat stress-induced mitochondrial fragmentation through mediating the expression of mitochondrial fission and fusion-related genes, including Dynamin related protein 1 (Drp1), Mitochondrial fission 1 protein (Fis1), and Mitofusin1, 2 (Mfn1, 2). Above all, our findings demonstrate that DMY could protect DCMECs against heat stress-induced injury through preventing oxidative stress, the imbalance of mitochondrial fission and fusion, which provides useful evidence that DMY can be a promising therapeutic drug for protecting heat stress-induced mammary glands injury and mastitis.


Asunto(s)
Flavonoles/farmacología , Respuesta al Choque Térmico/efectos de los fármacos , Sustancias Protectoras/farmacología , Animales , Apoptosis/efectos de los fármacos , Bovinos , Supervivencia Celular/efectos de los fármacos , Dinaminas , Células Epiteliales/efectos de los fármacos , Femenino , Mitocondrias/efectos de los fármacos , Dinámicas Mitocondriales/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos
5.
Ecotoxicol Environ Saf ; 214: 112080, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33677380

RESUMEN

Resveratrol (RES) is a natural polyphenolic compound with a broad range of physiological and pharmacological properties. Previous studies have shown that RES also plays an important role in protecting and promoting early bone metabolism and differentiation. The accumulation of cadmium (Cd), one of the world's most poisonous substances, can inhibit skeletal growth and bone maturation, thus causing osteoporosis. However, whether RES can prevent the Cd-induced inhibition of osteogenic differentiation remains unknown. In this study, we found that RES promoted the early maturity of osteoblastic MC3T3-E1 cells, as demonstrated by the significantly increased mRNA and protein expression of a range of differentiation markers, including alkaline phosphatase (ALP), collagen 1 (COL1), bone morphogenetic protein-2 (BMP-2), and runt-related transcription factor 2 (RUNX2). In contrast, we found that cadmium chloride (CdCl2) inhibited the viability and osteogenic maturity of MC3T3-E1 cells. We also demonstrated that RES pretreatment for 30 min provided significant protection against Cd-induced apoptosis and attenuated the inhibition of osteogenic differentiation induced by Cd by modulating ERK1/2 and JNK signaling. In conclusion, our results indicate that RES is a potential femoral protectant that not only enhance the viability and early differentiation of osteoblasts, but also protect osteoblasts from cadmium damage.


Asunto(s)
Cadmio/toxicidad , Sustancias Protectoras/farmacología , Resveratrol/farmacología , Fosfatasa Alcalina/metabolismo , Animales , Proteína Morfogenética Ósea 2 , Cadmio/metabolismo , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal , Sistema de Señalización de MAP Quinasas , Proteína Quinasa 3 Activada por Mitógenos , Osteoblastos/citología , Osteogénesis/genética
6.
Int J Mol Sci ; 22(4)2021 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-33669855

RESUMEN

Colitis is a multifactorial disorder that mostly occurs in the gastrointestinal tract. Despite improvements in mucosal inflammation research, little is known regarding the small bioactive molecules that are beneficial for regulating T cells and colon cell activity. 6,7,4'-trihydroxyflavanone (THF) is a flavanone that possesses anti-osteoclastogenesis activity and exerts protective effects against methamphetamine-induced immunotoxicity. Whether THF mitigates intestinal inflammation by regulating T cells and colon cell activity remains unknown. In the present study, Jurkat and HT-29 cells were used for in vitro experiments, and dextran sulfate sodium (DSS)-induced colitis model in mice was used for in vivo experiment. We observed that THF did not have a negative effect on the viability of Jurkat and HT-29 cells. Quantitative PCR and Western blot analysis revealed that THF regulates the activity of Jurkat cells and HT-29 cells via the NFκB and MAPK pathways under stimulated conditions. In the DSS-induced colitis model, oral administration of THF attenuated the manifestations of DSS-induced colitis, including a reduction in body weight, shrinkage of the colon, and enhanced expression of pro-inflammatory cytokines in the colon and mesenteric lymph nodes. These data suggest that THF alleviates DSS-induced colitis by modulating the activity of T cells and colon cells in vivo.


Asunto(s)
Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colon/inmunología , Colon/patología , Flavanonas/uso terapéutico , Sustancias Protectoras/uso terapéutico , Linfocitos T/inmunología , Administración Oral , Animales , Peso Corporal/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Colitis/inmunología , Citocinas/metabolismo , Sulfato de Dextran , Modelos Animales de Enfermedad , Femenino , Flavanonas/administración & dosificación , Flavanonas/química , Flavanonas/farmacología , Células HT29 , Humanos , Inflamación/patología , Intestinos/patología , Células Jurkat , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones Endogámicos C57BL , Sustancias Protectoras/farmacología , Linfocitos T/efectos de los fármacos , Células TH1/efectos de los fármacos , Células TH1/inmunología , Células Th17/efectos de los fármacos , Células Th17/inmunología , Factor de Transcripción ReIA/metabolismo
7.
Int J Mol Sci ; 22(4)2021 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-33670808

RESUMEN

Hepatic fibrosis occurs when liver tissue becomes scarred from repetitive liver injury and inflammatory responses; it can progress to cirrhosis and eventually to hepatocellular carcinoma. Previously, we reported that neoagarooligosaccharides (NAOs), produced by the hydrolysis of agar by ß-agarases, have hepatoprotective effects against acetaminophen overdose-induced acute liver injury. However, the effect of NAOs on chronic liver injury, including hepatic fibrosis, has not yet been elucidated. Therefore, we examined whether NAOs protect against fibrogenesis in vitro and in vivo. NAOs ameliorated PAI-1, α-SMA, CTGF and fibronectin protein expression and decreased mRNA levels of fibrogenic genes in TGF-ß-treated LX-2 cells. Furthermore, downstream of TGF-ß, the Smad signaling pathway was inhibited by NAOs in LX-2 cells. Treatment with NAOs diminished the severity of hepatic injury, as evidenced by reduction in serum alanine aminotransferase and aspartate aminotransferase levels, in carbon tetrachloride (CCl4)-induced liver fibrosis mouse models. Moreover, NAOs markedly blocked histopathological changes and collagen accumulation, as shown by H&E and Sirius red staining, respectively. Finally, NAOs antagonized the CCl4-induced upregulation of the protein and mRNA levels of fibrogenic genes in the liver. In conclusion, our findings suggest that NAOs may be a promising candidate for the prevention and treatment of chronic liver injury via inhibition of the TGF-ß/Smad signaling pathway.


Asunto(s)
Cirrosis Hepática/metabolismo , Cirrosis Hepática/prevención & control , Oligosacáridos/farmacología , Sustancias Protectoras/farmacología , Transducción de Señal , Proteínas Smad/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Animales , Tetracloruro de Carbono , Línea Celular , Regulación de la Expresión Génica/efectos de los fármacos , Células Estrelladas Hepáticas/efectos de los fármacos , Células Estrelladas Hepáticas/metabolismo , Humanos , Cirrosis Hepática/patología , Masculino , Ratones Endogámicos ICR
8.
Molecules ; 26(4)2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33672046

RESUMEN

Substituted N-phenyl cinnamamide derivatives were designed and synthesized to confirm activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway by the electronic effect on beta-position of Michael acceptor according to introducing the R1 and R2 group. Compounds were screened using the Nrf2/antioxidant response element (ARE)-driven luciferase reporter assay. Compound 1g showed desirable luciferase activity in HepG2 cells without cell toxicity. mRNA and protein expression of Nrf2/ARE target genes such as NAD(P)H quinone oxidoreductase 1, hemeoxygenase-1, and glutamate-cysteine ligase catalytic subunit (GCLC) were upregulated by compound 1g in a concentration-dependent manner. Treatment with 1g resulted in increased endogenous antioxidant glutathione, showing strong correlation with enhanced GCLC expression for synthesis of glutathione. In addition, tert-butyl hydroperoxide (t-BHP)-generated reactive oxygen species were significantly removed by 1g, and the results of a cell survival assay in a t-BHP-induced oxidative cell injury model showed a cytoprotective effect of 1g in a concentration dependent manner. In conclusion, the novel compound 1g can be utilized as an Nrf2/ARE activator in antioxidative therapy.


Asunto(s)
Cinamatos/farmacología , Citoprotección/efectos de los fármacos , Glutatión/biosíntesis , Hepatocitos/patología , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/efectos de los fármacos , Elementos de Respuesta Antioxidante/genética , Ácidos Carboxílicos/química , Ácidos Carboxílicos/farmacología , Muerte Celular/efectos de los fármacos , Cinamatos/química , Glutatión/metabolismo , Células Hep G2 , Hepatocitos/efectos de los fármacos , Humanos , Luciferasas/metabolismo , Factor 2 Relacionado con NF-E2/agonistas , Sustancias Protectoras/farmacología , terc-Butilhidroperóxido
9.
Cell Prolif ; 54(4): e13021, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33751704

RESUMEN

Although the liver is the only organ with regenerative capacity, various injury factors induce irreversible liver dysfunction and end-stage liver disease. Liver resection and liver transplantation (LT) are effective treatments for individuals with liver failure, liver cirrhosis and liver cancers. The remnant or transplanted liver tissues will undergo hepatic ischaemia/reperfusion (IR), which leads to oxidative stress, inflammation, immune injury and liver damage. Moreover, systemic ischaemia induced by trauma, stroke, myocardial ischaemia, haemorrhagic shock and other injury factors also induces liver ischaemia/reperfusion injury (IRI) in individuals. Hepatic IRI can be divided into warm IRI, which is induced by liver surgery and systemic ischaemia, and cold IRI, which is induced by LT. Multiple studies have shown that melatonin (MT) acts as an endogenous free radical scavenger with antioxidant capacity and is also able to attenuate hepatic IRI via its anti-inflammatory and antiapoptotic capacities. In this review, we discuss the potential mechanisms and current strategies of MT administration in liver surgery for protecting against warm or cold hepatic IRI. We highlight strategies to improve the efficacy and safety of MT for attenuating hepatic IRI in different conditions. After the potential mechanisms underlying the interactions between MT and other important cellular processes during hepatic IR are clarified, more opportunities will be available to use MT to treat liver diseases in the future.


Asunto(s)
Melatonina/uso terapéutico , Daño por Reperfusión/prevención & control , Antioxidantes/química , Apoptosis/efectos de los fármacos , Rechazo de Injerto/patología , Rechazo de Injerto/prevención & control , Humanos , Hígado/metabolismo , Hígado/patología , Melatonina/química , Melatonina/farmacología , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Sustancias Protectoras/farmacología , Sustancias Protectoras/uso terapéutico , Daño por Reperfusión/patología , Transducción de Señal/efectos de los fármacos
10.
Molecules ; 26(4)2021 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-33670455

RESUMEN

Many studies suggest anthocyanins may prevent the development of several diseases. However, anthocyanin bioactivity against cellular stress is not fully understood. This study aimed to evaluate the protective effect of berry anthocyanins on stressed cells using Saccharomyces cerevisiae. The impact of in vitro gastrointestinal digestion on anthocyanin profiles was also assessed. Bilberry and blackcurrant had higher anthocyanin levels than raspberry and strawberry, but digestion reduced the detected anthocyanins by approximately 90%. Yeast cells with and without digested or nondigested anthocyanin extracts were exposed to H2O2 and examined for survival. In the presence of anthocyanins, particularly from digested strawberry, a significant increase in cell survival was observed, suggesting that the type and levels of anthocyanins are important factors, but they also need to undergo gastrointestinal (GI) structural modifications to induce cell defence. Results also showed that cells need to be exposed to anthocyanins before the stress was applied, suggesting induction of a cellular defence system by anthocyanins or their derivatives rather than by a direct antioxidative effect on H2O2. Overall, data showed that exposure of severely stressed yeast cells to digested berry extracts improved cell survival. The findings also showed the importance of considering gastrointestinal digestion when evaluating anthocyanins' biological activity.


Asunto(s)
Frutas/química , Peróxido de Hidrógeno/toxicidad , Viabilidad Microbiana/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Saccharomyces cerevisiae/citología , Antocianinas/análisis , Antocianinas/química , Sustancias Protectoras/farmacología , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/crecimiento & desarrollo
11.
Life Sci ; 273: 119304, 2021 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-33662432

RESUMEN

AIMS: Necroptosis, an inflammatory form of regulated necrosis mediated by receptor-interacting kinase 1 (RIP1), RIP3, and pseudokinase mixed lineage kinase domain-like protein (MLKL) is extensively implicated in liver inflammatory disease. Thus identification small-molecule inhibitor of necroptosis has emerged as a potential therapeutic strategy to prevent liver damage. In this study, we identified 5-((7-chloro-6-fluoro-1 h-indol-3-yl) methyl)-3-methylimidazolidine-2,4-dione (F-nec) as a novel potent necroptosis inhibitor. MAIN METHODS: To find out the potent chemical inhibitors of necroptosis, human monocytic U937 cells were treated with a combination of tumor necrosis factor alpha (TNFα) and a pan-caspase inhibitor z-VAD-fmk. LPS and D-galactosamine (LPS/GalN) were further employed to simulate acute liver failure to explore therapeutic potency of F-nec in vivo. In addition, a specific inhibitor of c-Jun NH (2)-terminal kinases (JNK) SP600125 and its activator anisomycin are used to elucidate its mechanisms in acute liver failure therapy. Necroptosis pathway related proteins were tested by western blot. KEY FINDINGS: In this study, we identified F-nec as a novel potent RIP1 inhibitor which efficiently blocked TNFα-induced necroptosis in human and mice cells. Furthermore, pre-treatment of F-nec could prevent hepatic necrosis by reducing RIP1-mediated necroptosis also effectively ameliorated LPS/GalN induced acute liver failure by attenuating cell death signaling-stimulated JNK pathway activation and then suppressing JNK-triggered inflammation. SIGNIFICANCE: Altogether, this study demonstrates that F-nec is a potent inhibitor of RIP1 and highlights its great potential for use in the treatment of RIP1-driven inflammatory liver diseases.


Asunto(s)
Proteínas Activadoras de GTPasa/antagonistas & inhibidores , Galactosamina/toxicidad , Indoles/química , Lipopolisacáridos/toxicidad , Fallo Hepático Agudo/tratamiento farmacológico , Necroptosis , Sustancias Protectoras/farmacología , Animales , Humanos , Fallo Hepático Agudo/inducido químicamente , Fallo Hepático Agudo/metabolismo , Fallo Hepático Agudo/patología , Ratones , Ratones Endogámicos C57BL , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Células U937
12.
Life Sci ; 273: 119297, 2021 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-33689686

RESUMEN

Stress-induced gastritis is a common problem in the intensive care unit. Zeaxanthin (ZE), a non-provitamin A carotenoid has been known to exert antioxidant and anti-inflammatory effects. In this study, we examined the effect of ZE on water avoidance stress (WAS)-induced gastritis in rats. 24 Sprague' Dawley male rats were divided into four groups; control, ZE, WAS and WAS+ZE. In the stressed rats, treatment with ZE effectively downregulated the gastric levels of total oxidant status (TOS), myeloperoxidase (MPO) and malondialdehyde (MDA), with significant upregulation of the antioxidant enzymes' activities and gastric levels of prostagladin-E2 (PGE2) as compared to the untreated stressed one. As noticed in the present study, ZE significantly decrease the gastric levels of interleukin-1 ß (IL-1ß) and IL-6 as well as suppression of nuclear transcription factor kappa-B (NF-κB) immunohistochemical expression together with upregulation of trefoil factor-1 (TFF-1) gene expression. Moreover, in the untreated WAS-induced gastritis group, gastrin and corticosterone levels were significantly increased together with upregulation of the gene expression of hypoxia inducible factor-1α (HIF-1α), matrix metalloproteinase-9 (MMP-9), PI3K, Akt and JNK in the gastric tissues, which significantly improved by ZE administration. These all positive effects of ZE reflected on reduction of microscopic gastric mucosal damage and inflammatory cell infiltration with improvement of ulcer score. Our results discover that ZE has a new gastroprotective effect against stress-induced gastritis in rats, primarily through its antioxidative and anti-inflammatory effects, which are expressed in the regulation of the MMP-9 and HIF-1α signaling pathways.


Asunto(s)
Biomarcadores/análisis , Gastritis/tratamiento farmacológico , Regulación de la Expresión Génica/efectos de los fármacos , Sustancias Protectoras/farmacología , Estrés Fisiológico , Zeaxantinas/farmacología , Animales , Antioxidantes/metabolismo , Citocinas/metabolismo , Gastritis/etiología , Gastritis/metabolismo , Gastritis/patología , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , MAP Quinasa Quinasa 4/genética , MAP Quinasa Quinasa 4/metabolismo , Masculino , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Estrés Oxidativo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Sprague-Dawley , Factor Trefoil-1/genética , Factor Trefoil-1/metabolismo
13.
Int J Mol Sci ; 22(5)2021 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-33670975

RESUMEN

Excessive intake of fructose results in metabolic syndrome (MS) and kidney damage, partly mediated by its metabolism by fructokinase-C or ketohexokinase-C (KHK-C). Osthol has antioxidant properties, is capable of regulating adipogenesis, and inhibits KHK-C activity. Here, we examined the potential protective role of osthol in the development of kidney disease induced by a Western (high-fat/high-sugar) diet. Control rats fed with a high-fat/high-sugar diet were compared with two groups that also received two different doses of osthol (30 mg/kg/d or 40 mg/kg/d body weight BW). A fourth group served as a normal control and received regular chow. At the end of the follow-up, kidney function, metabolic markers, oxidative stress, and lipogenic enzymes were evaluated. The Western diet induced MS (hypertension, hyperglycemia, hypertriglyceridemia, obesity, hyperuricemia), a fall in the glomerular filtration rate, renal tubular damage, and increased oxidative stress in the kidney cortex, with increased expression of lipogenic enzymes and increased kidney KHK expression. Osthol treatment prevented the development of MS and ameliorated kidney damage by inhibiting KHK activity, preventing oxidative stress via nuclear factor erythroid 2-related factor (Nrf2) activation, and reducing renal lipotoxicity. These data suggest that the nutraceutical osthol might be an ancillary therapy to slow the progression of MS and kidney damage induced by a Western diet.


Asunto(s)
Cumarinas/farmacología , Dieta Occidental/efectos adversos , Fructoquinasas/antagonistas & inhibidores , Enfermedades Renales/prevención & control , Síndrome Metabólico/prevención & control , Animales , Cumarinas/uso terapéutico , Dieta de Carga de Carbohidratos/efectos adversos , Dieta Alta en Grasa/efectos adversos , Fructoquinasas/metabolismo , Fructosa/metabolismo , Enfermedades Renales/etiología , Enfermedades Renales/metabolismo , Masculino , Síndrome Metabólico/etiología , Síndrome Metabólico/metabolismo , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Sustancias Protectoras/farmacología , Sustancias Protectoras/uso terapéutico , Ratas , Ratas Wistar
14.
Life Sci ; 276: 119420, 2021 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-33785340

RESUMEN

Quercetin (Q) is formulated into oil-in-water F127 microemulsions to improve its bioavailability. The size of the Q-loaded microemulsions system was about 8 nm by dynamic light scattering analysis. To compare antioxidant activity of bulk solution and microemulsion of Q, free radical scavenging activity was evaluated against 2,2-diphenyl-1-picrylhydrazyl (DPPH). The IC50 values were 56.77 and 187.68 µM, respectively. The drug in the bulk form released 16.34 times faster than microemulsion form. Although gentamicin (GM) has potent efficacy against gram-negative bacteria, it induces renal toxicity. Poor solubility and low bioavailability of Q as a bioflavonoid with potent antioxidant activity, limit its therapeutic application. We aimed to compare the effect of free Q and nanoencapsulated (NEQ) against GM-induced renal damage in Wistar rats. Forty-two animals were divided into six groups. Control and GM groups received apo-nanomicelles and GM (100 mg/kg) for 10 days. Two groups received Q (50 mg/kg, i.g.) and NEQ (50 mg/kg, i.g.) respectively for 10 days. Remaining two groups received Q and NEQ (50 mg/kg, i.g.) plus GM (100 mg/kg, i.p.) simultaneously for 10 days. After the experiments, serum and kidneys were used for biochemical, molecular and histological examinations. Immunohistochemical analysis was performed to explore kidney injury molecule-1 (KIM-1) expression as a specific protein biomarker of renal injury. Our findings indicated oxidative stress and altered histological features in renal tissue with deviated serum renal biomarkers in GM-treated rats. Although Q treatment in GM group tried to protect against GM-induced nephrotoxicity, but there were still differences compared to control rats. However, NEQ administration corrected elevations in the levels of urea, creatinine, uric acid and decrements in serum total proteins of GM group. Meanwhile, NEQ restored renal oxidative injury in GM rats through attenuation of lipid peroxidation and enhancement of antioxidant defense systems, glutathione, catalase and superoxide dismutase. NEQ could also normalize GM-induced abnormal renal histology features including fibrosis. Furthermore, the result of immunohistochemistry study confirmed these findings by undetecting KIM-1 expression in NEQ treated GM group, meanwhile showing this renal biomarker in GM and Q treated GM groups. Therefore, NEQ seems to be useful in protecting against renal oxidative stress and kidney damage in a rat model of GM nephrotoxicity which deserve further evaluations.


Asunto(s)
Lesión Renal Aguda/tratamiento farmacológico , Antioxidantes/farmacología , Gentamicinas/toxicidad , Polietilenos/química , Polipropilenos/química , Sustancias Protectoras/farmacología , Quercetina/farmacología , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/patología , Animales , Antioxidantes/administración & dosificación , Antioxidantes/química , Biomarcadores/análisis , Nitrógeno de la Urea Sanguínea , Glutatión/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Sustancias Protectoras/administración & dosificación , Sustancias Protectoras/química , Quercetina/administración & dosificación , Quercetina/química , Ratas , Ratas Wistar
15.
Life Sci ; 276: 119434, 2021 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-33785343

RESUMEN

AIMS: Immunosuppressive myeloid-derived suppressor cells (MDSCs) continuously expand and lead to poor outcome during sepsis. The activation of liver X receptor (LXR) can mitigate sepsis-induced liver and myocardial damage. This study aims to determine whether LXR plays a protective role in sepsis by regulating MDSCs. MAIN METHODS: Cecal ligation and puncture(CLP)was used to induce sepsis in mice. The mice were then treated with LXR agonist GW3965 (3 mg/kg) or vehicle 1 h, 6 h, 12 h, 24 h, 48 h, 72 h postoperatively. The effect of LXR on the survival rate and multi-organ injury induced by sepsis was evaluated by survival analysis, histological staining, biochemical analysis and ELISAs. The percentages of MDSCs and T cells were detected using flow cytometry. The mRNA expressions of LXR and ATP-binding cassette transporter A1 (ABCA1) were measured using real-time quantitative PCR (RT-qPCR). ABCA1 protein level was determined using immunofluorescence staining. KEY FINDINGS: LXR agonist GW3965 treatment improved the survival of septic mice, accompanied by reduced multi-organ injury and a decreased level of inflammatory cytokines. Furthermore, GW3965 treatment decreased MDSCs abundance in spleen by boosting the apoptosis of spleen MDSCs, therefore ameliorating their immunosuppressive activity. Meanwhile, bacteria clearance in tissues was enhanced after the GW3965 administration in septic mice. Mechanistically, GW3965 activated LXRß and its downstream target ABCA1 to initiate the apoptosis of spleen MDSCs. SIGNIFICANCE: These findings provide new insights into the relationship between LXR and MDSCs in sepsis, thus revealing a potentially effective approach to target the immunosuppression of sepsis.


Asunto(s)
Apoptosis , Benzoatos/farmacología , Bencilaminas/farmacología , Receptores X del Hígado/agonistas , Células Supresoras de Origen Mieloide/patología , Sustancias Protectoras/farmacología , Sepsis/tratamiento farmacológico , Transportador 1 de Casete de Unión a ATP/genética , Transportador 1 de Casete de Unión a ATP/metabolismo , Animales , Citocinas/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Sepsis/metabolismo , Sepsis/patología
16.
Chem Biol Interact ; 338: 109402, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33587916

RESUMEN

Cisplatin is an important antineoplastic drug used in multiple chemotherapeutic regimens but unfortunately causes serious toxic effects as ovarian and uterine toxicity. This study aimed to investigate the potential protective effect of resveratrol (RSV) against cisplatin-induced ovarian and uterine toxicity in female rats. Thirty-two female Wistar rats were divided randomly into four groups (n = 8 in each). Control group received oral normal saline for 28 days; RSV group received RSV (10 mg/kg; daily) via oral gavage; CIS group received a single dose of CIS (7 mg/kg; i.p.) on the 21st day; (CIS + RSV) group received both RSV and CIS by the same schedules and doses of RSV and CIS groups, respectively. Results demonstrated a significant decrease in MDA level and a significant increase in both glutathione content and activity of the antioxidant enzymes GPx, SOD, and CAT in the tissues of the ovary and uterus of CIS + RSV group in comparison to that of CIS group (P<0.05), also there are significantly decreased tissue levels of the proinflammatory cytokines and enzymes (NF-κB, IL-1ß, IL-6, TNF-α, COX-2, and iNOS), increased estradiol, progesterone, prolactin and decreased FSH serum levels in CIS + RSV group compared to CIS group (P < 0.05). Moreover, there is downregulation of tissues Cleaved Caspase-3, NF-κB and Cox-2 proteins as shown in Western blot analysis, also apoptosis was significantly inhibited, evidenced by downregulation of Bax and upregulation of Bcl-2 proteins, and the ovarian and uterine histological architecture and integrity were maintained in CIS + RSV group compared to CIS group. In conclusion, these findings indicate that RSV has beneficial effects in ameliorating cisplatin-induced oxidative stress, inflammation, and apoptosis in the ovarian and uterine tissues of female rats.


Asunto(s)
Apoptosis/efectos de los fármacos , Cisplatino/efectos adversos , Inflamación/patología , Ovario/patología , Estrés Oxidativo/efectos de los fármacos , Sustancias Protectoras/farmacología , Resveratrol/farmacología , Útero/patología , Animales , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Catalasa/metabolismo , Ciclooxigenasa 2/metabolismo , Citocinas/metabolismo , Estradiol/sangre , Femenino , Hormona Folículo Estimulante/sangre , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Malondialdehído/metabolismo , Modelos Biológicos , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Ovario/efectos de los fármacos , Progesterona/sangre , Prolactina/sangre , Carbonilación Proteica/efectos de los fármacos , Ratas Wistar , Superóxido Dismutasa/metabolismo , Proteína X Asociada a bcl-2/metabolismo
17.
Life Sci ; 270: 119138, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33524422

RESUMEN

AIMS: Sodium propionate (SP) has been reported to possess an anti-inflammatory and anti-apoptotic potential by inhibiting certain signaling pathways and helps in reducing the pathological damages of the mammary gland. However, the effects of sodium propionate on attenuating Lipopolysaccharide (LPS)-induced inflammatory condition and cell damage in bovine mammary epithelial cells (bMECs) are not comprehensively studied yet. Therefore, the aim of the current investigation was to evaluate the protective effects of sodium propionate on LPS-induced inflammatory conditions and to clarify the possible underlying molecular mechanism in bMECs. MAIN METHODS: The effects of increasing doses of SP on LPS-induced inflammation, oxidative stress and apoptosis was studied in vitro. Furthermore, the underlying protective mechanisms of SP on LPS-stimulated bMECs was investigated under different experimental conditions. KEY FINDINGS: The results reveled that increased inflammatory cytokines, chemokines and those of tight junction's mRNA expression was significantly attenuated dose-dependently by propionate. Biochemical analysis revealed that propionate pretreatment modulated the LPS-induced intercellular reactive oxygen species (ROS) accumulation, oxidative and antioxidant factors and apoptosis rate. Furthermore, we investigated that the LPS activated nuclear factor-kB (NF-kB), caspase/Bax apoptotic pathways and Histone deacetylases (HDAC) was significantly attenuated by propionate in bMECs. SIGNIFICANCE: Our results suggest that sodium propionate is a potent agent for ameliorating LPS-mediated cellular disruption and limiting detrimental inflammatory responses, partly via maintaining blood milk barrier integrity, inhibiting HDAC activity and NF-kB signaling pathway.


Asunto(s)
Leche/efectos de los fármacos , Propionatos/farmacología , Animales , Antiinflamatorios/farmacología , Apoptosis/efectos de los fármacos , Bovinos , Células Cultivadas , China , Citocinas/metabolismo , Células Epiteliales/metabolismo , Femenino , Inflamación/patología , Lipopolisacáridos/farmacología , Glándulas Mamarias Animales/efectos de los fármacos , Glándulas Mamarias Animales/metabolismo , Leche/metabolismo , FN-kappa B/metabolismo , Propionatos/metabolismo , Sustancias Protectoras/farmacología , Transducción de Señal/efectos de los fármacos
18.
Ecotoxicol Environ Saf ; 213: 111987, 2021 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-33582408

RESUMEN

Protective effects of estrogen (E2) on traumatic brain injury (TBI) have been determined. In this study, the hepatoprotective effects of E2 after TBI through its receptors and oxidative stress regulation have been evaluated. Diffuse TBI induced by the Marmarou method in male rats. G15, PHTPP, MPP, and ICI182-780 as selective antagonists of E2 were injected before TBI. The results indicated that TBI induces a significant increase in liver enzymes [Alkaline phosphatase (ALP), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Glutamyl transferase (GGT)], and oxidants levels [Malondialdehyde (MDA), Nitric oxide (NO)] and decreases in antioxidant biomarkers [Glutathione peroxidase (GPx) and Superoxide dismutase (SOD)] in the brain and liver, and plasma. We also found that E2 significantly preserved levels of these biomarkers and enzymatic activity. All antagonists inhibited the effects of E2 on increasing SOD and GPx. Also, the effects of E2 on brain MDA levels were inhibited by all antagonists, but in the liver, only ICI + G15 + E2 + TBI group was affected. The impacts of E2 on brain and liver and plasma NO levels were inhibited by all antagonists. The current findings demonstrated that E2 probably improved liver injury after TBI by modulating oxidative stress. Also, both classic (ERß, ERα) and non-classic [G protein-coupled estrogen receptor (GPER)] receptors are affected in the protective effects of E2.


Asunto(s)
Estradiol/farmacología , Sustancias Protectoras/farmacología , Alanina Transaminasa/metabolismo , Animales , Antioxidantes/metabolismo , Aspartato Aminotransferasas/metabolismo , Lesiones Traumáticas del Encéfalo/metabolismo , Estradiol/metabolismo , Receptor alfa de Estrógeno/metabolismo , Receptor beta de Estrógeno/metabolismo , Estrógenos/metabolismo , Glutatión Peroxidasa/metabolismo , Hígado/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Receptores Estrogénicos/metabolismo , Superóxido Dismutasa/metabolismo
19.
Int J Mol Med ; 47(4)2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33537804

RESUMEN

Quercetin (Quer) is a typical antioxidant flavonoid from plants that is involved in bone metabolism, as well as in the progression of inflammatory diseases. Elevated levels of tumor necrosis factor­α (TNF­α), a typical pro­inflammatory cytokine, can affect osteogenesis. In the present study, TNF­α was used to establish an in vitro model of periodontitis. The effects of Quer on, as well as its potential role in the osteogenic response of human periodontal ligament stem cells (hPDLSCs) under TNF­α­induced inflammatory conditions and the underlying mechanisms were then investigated. Within the appropriate concentration range, Quer did not exhibit any cytotoxicity. More importantly, Quer significantly attenuated the TNF­α induced the suppression of osteogenesis­related genes and proteins, alkaline phosphatase (ALP) activity and mineralized matrix in the hPDLSCs. These findings were associated with the fact that Quer inhibited the activation of the NF­κB signaling pathway, as well as the expression of NLRP3 inflammation­associated proteins in the inflammatory microenvironment. Moreover, the silencing of NLRP3 by small interfering RNA (siRNA) was found to protect the hPDLSCs against TNF­α­induced osteogenic damage, which was in accordance with the effects of Quer. On the whole, the present study demonstrates that Quer reduces the impaired osteogenesis of hPDLSCs under TNF­α­induced inflammatory conditions by inhibiting the NF­κB/NLRP3 inflammasome pathway. Thus, Quer may prove to be a potential remedy against periodontal bone defects.


Asunto(s)
Inflamasomas/metabolismo , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Osteogénesis/efectos de los fármacos , Ligamento Periodontal/patología , Quercetina/farmacología , Células Madre/patología , Factor de Necrosis Tumoral alfa/toxicidad , Adolescente , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Citocinas/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Silenciador del Gen/efectos de los fármacos , Humanos , Mediadores de Inflamación/metabolismo , Sustancias Protectoras/farmacología , Transducción de Señal/efectos de los fármacos , Células Madre/efectos de los fármacos , Adulto Joven
20.
Int J Mol Med ; 47(4)2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33537813

RESUMEN

The activation of oxidative stress is a primary cause of chondrocyte apoptosis in osteoarthritis (OA). The 78­kDa glucose­regulated protein (GRP78)/mammalian target of rapamycin (mTOR) signaling pathway has been demonstrated to be linked with the endoplasmic reticulum (ER) and autophagy. Hydrogen sulfide (H2S) has been reported to exert antioxidant effects. The present study investigated oxidative stress levels via 2',7'­dichlorofluorescin diacetate and MitoSOX staining, apoptosis rates via flow cytometry and the expression levels of ER stress­related proteins in GYY4137 (donor of H2S)­treated chondrocytes (CHs). CHs were isolated from the bilateral hip joints of male rats to examine mitochondrial permeability transition pore opening­ and mTOR signaling pathway­related proteins. The results demonstrated that tert­Butyl hydroperoxide (TBHP) increased CH apoptosis, and treatment with GYY4137 ameliorated TBHP­mediated the generation of ROS and CH apoptosis. Moreover, TBHP­treated CHs displayed elevated ER stress sensor expression levels and apoptotic rates; however, the TBHP­induced protein expression levels were decreased following GYY4137 treatment. In the present study, treatment with either GYY4137 or transfection with GRP78 siRNA both suppressed the activation of p­P70S6k and p­mTOR. H2S played an important role in regulating ER stress in TBHP­stimulated CHs. GYY4137 promoted autophagy, which was accompanied by the inhibition of ER stress. On the whole, the present study demonstrates that TBHP­induced oxidative stress stimulates ER interactions and CH apoptosis, which are suppressed by exogenous H2S via modulating the GRP78/mTOR signaling pathway.


Asunto(s)
Condrocitos/metabolismo , Condrocitos/patología , Estrés del Retículo Endoplásmico/efectos de los fármacos , Proteínas de Choque Térmico/metabolismo , Sulfuro de Hidrógeno/farmacología , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Animales , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Hipoxia de la Célula/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cloroquina/farmacología , Condrocitos/efectos de los fármacos , Citoprotección/efectos de los fármacos , Masculino , Morfolinas/química , Morfolinas/farmacología , Compuestos Organotiofosforados/química , Compuestos Organotiofosforados/farmacología , Peróxidos/farmacología , Sustancias Protectoras/farmacología , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos
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