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1.
J Agric Food Chem ; 67(46): 12844-12853, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31668063

RESUMO

Flazin is a ß-carboline-derived alkaloid found in Japanese fermented foods. Here, the potential of flazin as an antioxidant food was studied with particular reference to its effect on the Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) system in human hepatocytes (C3A). Flazin and flazin analogues including the decarboxylated derivative perlolyrine were chemically synthesized and compared with each other and with chlorogenic acid and curcumin. Among these compounds, flazin showed the lowest cytotoxicity (IC50 < 500 µM) and the highest capacity to activate the Keap1-Nrf2 system. It provided the largest (>3-fold of the control) cytoprotection ability against a pro-oxidant, although its radical absorbance capacity was relatively low. Flazin increased the expressions of Nrf2-dependent phase II enzyme genes and their products (NQO1, GSTP, and GSH proteins). The strong cytoprotection ability of flazin associated with low log P (0-3) is shared by sulforaphane and 3,5-dihydroxy-4-methoxybenzyl alcohol, suggesting the potential value of flazin and flazin-rich foods for the prevention of oxidation-related health disorders.


Assuntos
Carbolinas/farmacologia , Furanos/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/genética , Transdução de Sinais/efeitos dos fármacos
2.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(4): 317-321, 2019 Jul 28.
Artigo em Chinês | MEDLINE | ID: mdl-31701714

RESUMO

OBJECTIVE: To apply hypoxia of different oxygen concentration on C2C12 cells to study the changes of Nrf2 antioxidant system under H2O2. METHODS: The perfect simulative effect time and concentration of H2O2 were chosen. Cell vitality was tested after C2C12 cells cultured in 0.1 mmol/L, 0.25 mmol/L, 0.5 mmol/L, 0.75 mmol/L, 1 mmol/L and 2 mmol/L H2O2 for 1 or 2 h respectively. The C2C12 cells were divided into different oxygen concentration group: 21%O2, 12%O2, 8%O2, 5%O2 respectively. And then cells were treated with H2O2 for 1 h, and collected for determination. Immunofluorescence of Nrf2 and the protein expression of Nrf2 were detected. The expressions of antioxidant enzymes superoxide dismutase 1 (SOD1), superoxide dismutase 2 (SOD2), catalase(CAT), NADPH quinine oxidoreductase-1 (NQO-1), glutathione peroxidase-1 (GPX-1), Heme oxygenase-1 (HO-1) mRNA and cellular ROS levels were tested by high quality fluorescence assay. RESULTS: 0.5 mmol/L H2O2 for 1 h was selected as the conditions of H2O2stimulation. Compared with 21% O2 group, the expressions of Nrf2 mRNA and protein, antioxidant enzymes SOD1, SOD2, CAT, HO-1, NQO-1, GPX-1 mRNA were increased significantly (P<0.05 or P<0.01), and ROS level was lower (P<0.01) in 12%O2 group cells; only the expression of GPX-1 mRNA was increased (P<0.05) in 8%O2 group; the expressions of Nrf2 mRNA and protein expression, antioxidant enzymes SOD1, SOD2, NQO-1, GPX-1 mRNA were decreased significantly(P<0.05 or P<0.01), and ROS level was higher (P<0.01) in 5%O2 group. CONCLUSION: Hypoxia can affect the Nrf2 antioxidant system, and the different oxygen concentrations have different impact. In addition, 12% O2 for 12 h could promote the Nrf2 antioxidant system, and 5% extremely low oxygen may inhibit it.


Assuntos
Antioxidantes/metabolismo , Mioblastos/enzimologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Animais , Linhagem Celular , Sobrevivência Celular , Peróxido de Hidrogênio , Camundongos , Oxigênio , Espécies Reativas de Oxigênio/metabolismo
3.
Anticancer Res ; 39(11): 5911-5918, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704815

RESUMO

BACKGROUND/AIM: Double-negative T (DNT) cells are phenotypically CD3+CD4-CD8-T cells. This study aimed to investigate the anti-cancer activity of DNT cells against pancreatic cancer cells. MATERIALS AND METHODS: DNT cells were isolated from human peripheral blood. The effect of DNT cells on proliferation and invasion of the human pancreatic cell line Panc-1 was assessed. Expression of Nrf2 and Fas in Panc-1 cells co-cultured with DNT cells was analyzed with RT-PCR. The supernatants of Panc-1 and DNT co-cultures were analyzed with ELISA for IFN-r and FasL levels. RESULTS: The isolated DNT cell phenotype was CD4-CD8-CD56- CD3+TCR (T cell receptor) α/ß+ T cells with more than 90% purity. Panc-1 cell proliferation was significantly inhibited by co-culture with DNT cells. Panc-1 cells co-cultured with DNT cells showed significantly reduced cell invasion. Panc-1 cells co-cultured with DNT cells showed increased Nrf2 and Fas mRNA expression. Increased INF-r and FasL levels were detected in the supernatants of co-cultures of DNT and pancreatic cells. CONCLUSION: DNT cells inhibited proliferation and invasion of human pancreatic cancer cells. The INF-r, Fas/FasL pathway and Nrf2 may be involved in the anti-cancer effect of DNT cells against human pancreatic cancer.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Técnicas de Cocultura/métodos , Ativação Linfocitária/imunologia , Neoplasias Pancreáticas/prevenção & controle , Apoptose , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Proliferação de Células , Proteína Ligante Fas/metabolismo , Humanos , Fator 2 Relacionado a NF-E2/metabolismo , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Receptores de Interferon/metabolismo , Células Tumorais Cultivadas , Receptor fas/metabolismo
4.
J Environ Pathol Toxicol Oncol ; 38(2): 143-152, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679277

RESUMO

The current study evaluated the cardioprotective activity of genistein in cases of doxorubicin-(Dox) induced cardiac toxicity and a probable mechanism underlying this protection, such as an antioxidant pathway in cardiac tissues. Animals used in this study were categorized into four groups. The first group was treated with sodium carboxymethylcellulose (0.3%; CMC-Na) solution. The second group received Dox (3.0 mg/kg, i.p.) on days 6, 12, 18, and 24. The third and fourth groups received Dox (3 mg/kg, i.p.) on days 6, 12, 18, and 24 and received protective doses of genistein (100 [group 3] and 200 [group 4] mg/kg/day, p.o.) for 30 days. Treatment with genistein significantly improved the altered cardiac function markers and oxidative stress markers. This was coupled with significant improvement in cardiac histopathological features. Genistein enhanced the Nrf2 and HO-1 expression, which showed protection against oxidative insult induced by Dox. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed substantial inhibition of apoptosis by genistein in myocardia. The study showed that genistein has a strong reactive oxygen species scavenging property and potentially (P ≤ .001) decreases the lipid peroxidation as well as inhibits DNA damage in cardiac toxicity induced by Dox. In conclusion, the potential antioxidant effect of genistein may be because of its modulatory effect on Nrf2/HO-1 signalling pathway and by this means exhibits cardioprotective effects from Dox-induced oxidative injury.


Assuntos
Cardiotônicos/farmacologia , Cardiotoxinas/toxicidade , Doxorrubicina/toxicidade , Genisteína/farmacologia , Heme Oxigenase-1/genética , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo/efeitos dos fármacos , Animais , Cardiotoxicidade/etiologia , Heme Oxigenase-1/metabolismo , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Ratos , Ratos Wistar
5.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3494-3501, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602914

RESUMO

The aim of this paper was to compare the performance of acute liver injury in mice induced by Tripterygium Glycosides Tablets from 6 different manufacturers,and to explore the toxicity mechanism from the perspective of oxidative stress and apoptosis preliminarily. Male or female mice were randomly divided into normal group,Zhejiang group,Hunan group,Hubei group,Shanghai group,Jiangsu group and Fujian group. Mice in Tripgerygium Glycosides Tablets groups were given 16 times the clinical equivalent dose( 300 mg·kg-1) Tripgerygium Glycosides Tablets by oral administration for one time,mice were executed in 24 h after lavaged.Then the visceral brain coefficient of the organ was calculated. Histopathological changes of liver were observed by hematoxylin-eosin staining. Td T-mediated d UTP nick-end labeling was used to detect the apoptosis of the liver cells and the protein content of oxidative stress related factors in liver homogenate. Nuclear transcription factor E2-related factor( Nrf2) and heme oxygenase-1( HO-1) as well as mitochondrial mediated apoptosis-related protein expression levels of Bax and Bcl-2 in hepatic tissue were measured by Western blot.Within 24 hours of administration,6 male mice in Jiangsu group and 2 female mice in Zhejiang group were dying; compared with normal ones,liver coefficients of mice in Zhejiang,Shanghai,Jiangsu and Hunan groups were significantly increased,thymus coefficients in the first two groups were significantly reduced,as well as the lung coefficients of Fujian group mice,the rest was normal. In addition to Hubei group,serum AST,ALT or ALP levels of mice were increased,while TBi L were not being affected. Histopathological changes and apoptosis of liver cells were observed in all mice,and the degree of severity was ranked as Jiangsu,Zhejiang,Shanghai,Hunan,Hubei and Fujian group. All Tripterygium Glycosides Tablets increased the MDA and reduced the content of T-SOD,CAT or GSH in liver tissue while inhibited Nrf2,HO-1 and Bcl-2,increased the protein expression level of Bax( except Hunan group). Tripgerygium Glycosides Tablets from 6 manufacturers all resulted in liver function damage and liver histopathological changes,especially in Jiangsu,Hubei and Fujian,and the mechanism may related to inhibit Nrf2/HO-1 oxidative stress pathway and activate Bax/Bcl-2 apoptosis pathway to mediate lipid peroxidation and induce liver cell apoptosis. Triptolide A may be one of the main toxic components of Tripgerygium Glycosides Tablets that causing drug-induced liver injury. This study was conducted on normal mice with super dose medication,so the relevant results are for reference only.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas/toxicidade , Glicosídeos/toxicidade , Tripterygium/toxicidade , Animais , Apoptose , Feminino , Heme Oxigenase-1/metabolismo , Peroxidação de Lipídeos , Fígado/efeitos dos fármacos , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Distribuição Aleatória , Comprimidos , Proteína X Associada a bcl-2/metabolismo
6.
Life Sci ; 237: 116944, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31604108

RESUMO

AIMS: Endoplasmic reticulum stress (ERS) is an evolutionarily conserved cell stress response. Recently, it was found that ERS induces not only apoptosis but also endoplasmic reticulophagy (ER-phagy). A previous study demonstrated that inhibition of ER-phagy alleviates cell injury. The purpose of this study was to investigate the involvement of the protein kinase R-like ER kinase (PERK)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in ERS-induced ER-phagy in H9c2 cardiomyoblasts. To address this aim, cells were treated with ERS inhibitors and a Nrf2 inhibitor before establishment of thapsigargin (TG)- or tunicamycin (TM)-induced ERS models in H9c2 cardiomyoblasts. MAIN METHODS: Transmission electron microscopy and immunofluorescence staining were used to detect ER-phagy. Western blotting was employed to detect the levels of calreticulin (CRT), total and phosphorylated PERK, nuclear Nrf2, activated transcription factor 4 (ATF4), light chain 3B (LC3B)-II and Beclin 1. Immunofluorescence staining was used to assess subcellular location of Nrf2. KEY FINDING: TG or TM induced H9c2 cell injury and ER-phagy and upregulated CRT expression, PERK phosphorylation, Nrf2 nuclear translocation, and expression of ATF4, Beclin 1, and LC3B-II compared with control cells. Treatment with ERS inhibitors decreased TG- or TM-induced ER-phagy, downregulated CRT expression, PERK phosphorylation, Nrf2 nuclear translocation and the expression of ATF4, Beclin 1 and LC3B-II. Moreover, a Nrf2 inhibitor downregulated the expression of ATF4, Beclin 1 and LC3B-II and alleviated TG- or TM-induced ER-phagy and H9c2 cell injury. SIGNIFICANCE: These findings suggest that the PERK/Nrf2 pathway mediates upregulation of ER-phagy, thereby inducing cell injury in H9c2 cardiomyoblasts.


Assuntos
Apoptose , Estresse do Retículo Endoplasmático , Retículo Endoplasmático/patologia , Miócitos Cardíacos/patologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , eIF-2 Quinase/metabolismo , Fator 4 Ativador da Transcrição/metabolismo , Animais , Proteína Beclina-1/metabolismo , Células Cultivadas , Retículo Endoplasmático/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Miócitos Cardíacos/metabolismo , Fosforilação , Ratos , Transdução de Sinais
7.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(3): 317-322, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31631596

RESUMO

Objective: To explore the molecular mechanism of ventilation induced lung injury (VILI) formation based on Keap1/Nfr2/ARE signaling pathway. Methods: The VILI model was established by excessive mechanical ventilation in SD rats. HE staining was used to detect the pathological changes of lung tissue in the control group, normal tidal volume (VT) group and large VT group (VT 40 mL/kg). The wet weight of lung tissue was detected in each group. Dry weight (W/D) ratio change; BCA method was used to detect the changes of total protein in bronchoalveolar lavage fluid (BALF) of each group; ELISA was used to detect interleukin-1ß (IL-1ß) and leukocyte in BALF and serum of each group. The content of 8-OHdG in the lung tissue was detected by IL-8 and the content of malondialdehyde (MDA) in the lung tissue was detected by TBA method. The NLRP3, ASC and caspase-1 proteins in macrophages were detected by Western blot. The changes of Keap1 and Nrf2 proteins in lung tissues were detected by RT-PCR. The expressions of SOD mRNA and HO-1 mRNA in lung tissues of each group were detected by RT-PCR. Results: Excessive mechanical ventilation could damage lung tissue, leading to alveolar rupture, inflammatory cell infiltration and erythrocytosis. Compared with the control group and normal VT group, the W/D value, 8-OHdG and MDA content in the large VT group, and total BALF, the contents of IL-1ß and IL-18 in protein, IL-1ß, IL-18 in serum increased significantly ( P<0.05). Compared with the control group and normal VT group, NLRP3, ASC, in macrophage of large VT group, the content of Keap1 protein in caspase-1 protein and lung tissue increased significantly ( P<0.05). The expression of Nrf2 protein, SOD mRNA and HO-1 mRNA in lung tissue decreased significantly. Conclusions: Large VT ventilation can cause acute inflammatory injury in lung tissue and lead to the occurrence of VILI. Inflammatory bodies of NLRP3 in alveolar macrophages are involved in this process, and the mechanism of NLRP3 inflammatory bodies is caused by hyperventilation in addition to mechanical injury. Decreased Keap1/Nrf2-ARE pathway inhibition and ROS clearance may also cause macrophage production of NLRP3 inflammatory bodies.


Assuntos
Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais , Lesão Pulmonar Induzida por Ventilação Mecânica/metabolismo , Animais , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Heme Oxigenase (Desciclizante)/metabolismo , Interleucina-18/análise , Interleucina-1beta/análise , Pulmão , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo
8.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(3): 334-338, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31631599

RESUMO

Objective: To study the mechanism of renal injury in Lepr db/ db mice with the leptin receptor homozygous deficiency. Methods: Ten male of 28-week-old Lepr db/+ mice with leptin receptor heterozygous deficiency were selected as control group and ten male Lepr db/ db mice with leptin receptor homozygous deficiency were used in this study. After fasting for 8 hours, the body mass, fasting blood glucose (FBG) and glycosylated hemoglobulin (HbA1c) of the mice were measured. Blood of the mice was obtained from femoral artery before euthanasia. Serum creatinine (CRE), blood urea nitrogen (BUN), superoxide dismutase (SOD), glutathione (GSH) and malonaldehyde (MDA) were detected by corresponding kits, and serum interleukin-1ß (IL-1ß), monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) were measured using enzyme-linked immunosorbent assay (ELISA) method. The kidney was taken for pathological observation. The expression levels of nuclear factor E2-related factor 2 (Nrf2) and nuclear factor kappa B (NF-κB) in renal were analyzed by Western blot. The mitochondria of renal was isolated by the corresponding kit. Meanwhile, the expression level of lipoic acid synthase (LIAS) in renal mitochondria was measured by Western blot. Results: The body mass, FPG, HbA1c, CRE and BUN levels of the Lepr db/ db mice were significantly increased in comparison with the Lepr db/+ mice ( P<0.05). Compared with the Lepr db/+ mice, the Lepr db/ db mice renal exhibited glomerular hypertrophy, thickened basement membrane and capillary wall, the mesangial matrix expansion and mesangial cell hyperplasia. Compared with the Lepr db/+ mice, the serum level of GSH in the Lepr db/ db mice was decreased significantly ( P<0.05). The levels of MDA and concentrations of MCP-1, IL-1ß and TNF-α in serum of the Lepr db/ db mice were higher than those of the Lepr db/+ mice ( P<0.05). Compared with the Lepr db/+ mice, the expression of LIAS and Nrf2 protein in the Lepr db/ db mice renal were decreased ( P<0.05), while the expression of NF-κB protein was increased ( P<0.05). Conclusion: LIAS, Nrf2 and NF-κB might play significant roles through regulation of oxidative stress and inflammation in the renal injury of Lepr db/ db mice.


Assuntos
Rim/patologia , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Receptores para Leptina/genética , Sulfurtransferases/metabolismo , Animais , Masculino , Camundongos , Camundongos Knockout , Estresse Oxidativo
9.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(4): 533-539, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31642231

RESUMO

OBJECTIVE: To investigate the protective effect of (2R, 3R)-dihydroquercetin 7-O-ß-D-glucopyranose (C1) extracted from Coreopsis tinctoria Nutt. in a mouse model of alcoholic acute pancreatitis (FAEE-AP) induced byfatty acid ethyl ester (FAEE). METHODS: The 30 healthy SPF mice were randomly divided into control group, model group, low dose group, middle dose group and high dose group, 6 in each group. Alcoholic pancreatitis was induced by ethanol and palmitoleic acid administration (1.75 g/kg ethanol, 200 mg/kg palmitoleic acid, 2 times peritoneal injections). The three treatment groups were given C1 (0 h, 4 h, 8 h) at the dose of 12.5, 25 and 50 mg/kg, respectively. After 24 h of molding, the serum amylase, lipase and IL-6 levels were detected. The trypsin level in pancreatic tissue and myeloperoxidase (MPO) level in pancreatic and lung tissue were detected. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of pancreatic tissue and immunohistochemical (IHC) staining was used to detect the expression of nuclear factor-erythroid 2 related factor 2 (Nrf2) in pancreatic tissue. RESULTS: The pancreatic histopathological scores, serum amylase and lipase activity, trypsin level in pancreatic tissue, serum IL-6 level, MPO level of pancreas and lung were significantly higher in the model group than in the control group (P < 0.01). Compared with the model group, the pancreatic histopathologies of the low dose group was significantly improved (P < 0.05), as well as the serum amylase and lipase activity, trypsin level of pancreas, serum IL-6 level, the pancreas andthe lung's MPO level decreased significantly (P < 0.05), and up-regulate that expression of Nrf2 in pancreatic tissue. CONCLUSION: 12.5 mg/kg of (2R, 3R) -dihydroquercetin 7-O-ß-D-glucopyranose (C1) improved the expression of Nrf2, reduced the expression of inflammatory factor IL-6, and protected acute pancreatitis caused by FAEE.


Assuntos
Coreopsis/química , Glicosídeos/farmacologia , Pancreatite Alcoólica/tratamento farmacológico , Quercetina/farmacologia , Doença Aguda , Animais , Modelos Animais de Doenças , Interleucina-6/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Pâncreas , Quercetina/análogos & derivados , Distribuição Aleatória
10.
Cell Biochem Biophys ; 77(4): 367-377, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31659617

RESUMO

Cisplatin is a widely used anti-cancer drug. However, cisplatin is limited in clinical treatment because of its severe nephrotoxicity. This study reported whether O-GSP can antagonize the cisplatin-induced cytotoxicity in HEK293 cells through inducing HO-1 protein expression. We previously demonstrated O-GSP can increase the survival rate of HEK293 and have protective effect on HEK293 cells. Herein, We found that O-GSP can antagonize cisplatin nephrotoxicity through regulating the expression of HO-1. O-GSP promotes the translocation of Nrf2 in the nucleus, and activates the ERKN JNK pathway and p38 MAPK pathway. Interestingly, p38 MAPK plays a major role in HO-1 expression induced by O-GSP. And O-GSP can modulate the decrease of Nrf2 and HO-1 expression induced by cisplatin, and improve the cisplatin-induced activity and apoptosis rate of cells by stimulating the expression of HO-1. However, the protective effects of O-GSP are inhibited by ZnPP IX. Collectively, the results indicated that O-GSP induced the expression of HO-1 through p38MAPK and Nrf2 pathway in HEK293 cells.


Assuntos
Antineoplásicos/farmacologia , Biflavonoides/farmacologia , Catequina/farmacologia , Cisplatino/farmacologia , Heme Oxigenase-1/metabolismo , Proantocianidinas/farmacologia , Regulação para Cima/efeitos dos fármacos , Vitis/química , Apoptose/efeitos dos fármacos , Núcleo Celular/metabolismo , Células HEK293 , Humanos , Fator 2 Relacionado a NF-E2/metabolismo , Sementes/química , Sementes/metabolismo , Transdução de Sinais/efeitos dos fármacos , Vitis/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
11.
Zhonghua Gan Zang Bing Za Zhi ; 27(9): 677-680, 2019 Sep 20.
Artigo em Chinês | MEDLINE | ID: mdl-31594091

RESUMO

Objective: To study the effect of benazepril on the expression of nuclear factor E2 related factor 2 (Nrf2), nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) and reactive oxygen species (ROS) concentration in rats with hepatic fibrosis and to explore the possible antifibrotic mechanism of benazepril. Methods: Twenty-two healthy male Sprague-Dawley rats were randomly divided into 3 groups: control group (6 rats), model group (8 rats) and benazepril treatment group (8 rats). Two rats died during modeling and treatment in the model group and the benazepril treatment group, and a model of hepatic fibrosis induced by carbon tetrachloride (CCL(4)) was established. The rats in benazepril group were given benazepril for 8 weeks by gastric gavage. The assessment of liver tissue damage in each group was measured using conventional hematoxylin-eosin and Masson staining. The mRNA level of Nrf2, NOX4 in liver tissue was detected by RT-PCR, and serum ROS concentration was determined by colorimetry. All data were expressed in mean ± standard deviations, and were analyzed using SPSS21.0 statistical software. The data were compared using one-way analysis of variance, and the LSD-t method was used for pairwise comparison between the two groups. The correlation analysis was performed by Spearman's correlation analysis. Results: In the liver of the model group, with the aggravation of liver fibrosis the expression of Nrf2mRNA, NOX4 mRNA and ROS concentration were higher than control group [(4.01 ± 3.40), (31.78 ± 3.96), (1.82 ± 0.46) µg/ ml vs. (0.12 ± 0.11), (2.03 ± 0.31), (1.56±0.84) µg/ml, P < 0.05]. After benazepril treatment, NOX4 mRNA expression and ROS concentration were decreased than the model group [(15.93 ± 5.01), (0.78 ± 0.44) µg/ml vs. (31.78 ± 3.96), (1.82 ± 0.46) µg /ml, P < 0.05], while Nrf2 mRNA expression was higher than the model group [(6.69 ± 4.86) vs. (4.01 ± 3.40), P < 0.05]. There was a positive correlation between Nrf2 and NOX4, Nrf2 and ROS, and NOX4 and ROS (r = 0.616, 0.411, 0.802, P < 0.05). Conclusion: Benazepril may exert an anti-hepatic fibrosis effect by activating Nrf2 expression, or may inhibit the ROS-mediated oxidative stress in response to NOX4.


Assuntos
Benzazepinas/farmacologia , Cirrose Hepática/tratamento farmacológico , NADPH Oxidase 4/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Cirrose Hepática/metabolismo , Masculino , Estresse Oxidativo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
12.
Chem Biol Interact ; 314: 108847, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31610155

RESUMO

Lead (Pb) is one of the toxic heavy metals that have several toxicological implications including cytotoxicities and oxidative stress. The release of reactive oxygen species (ROS) usually initiates lipid peroxidation and resulting in inflammation and tissue injury. However, the detailed identification of the Pb-produced lipid hydroperoxides has received little attention. Furthermore, the mechanisms behind such effects are less informed. Therefore, this study firstly investigated Pb-produced lipid hydroperoxides in human HepG2 cells using LC/MS. The effects of Pb on the antioxidant enzymes were additionally examined using qPCR and their dependent activities. As a protection trial, the ameliorative effects of rosmarinic (RMA) and ascorbic (ASA) acids on Pb-induced cytotoxicity and oxidative stress and their regulatory effects on Nrf2/Keap1 pathway were investigated. The achieved results confirmed cytotoxicity and oxidative damage of Pb on HepG2 cells. In addition, 20 lipid hydroperoxides (LOOH) were identified including 11 phosphatidylcholine hydroperoxides (PCOOH), 5 triacylglycerol hydroperoxides (TGOOH) and 4 cholesteryl ester hydroperoxides (CEOOH). The most dominant LOOH species were PCOOH 34:2, PCOOH 34:3, PCOOH 38:7, TGOOH 60:14, TGOOH 60:15, CEOOH 18:3 and CEOOH 20:4. Pb significantly downregulated Nrf2-regulated antioxidant enzymes at both the pretranscriptional and functional levels. Co-exposure of HepG2 cells to RMA and ASA significantly reduced Pb-produced adverse outcomes. This protection occurred via activation Nrf2-Keap1 antioxidant pathway.


Assuntos
Antioxidantes/metabolismo , Ácido Ascórbico/química , Cinamatos/química , Depsídeos/química , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Chumbo/química , Fator 2 Relacionado a NF-E2/metabolismo , Ácido Ascórbico/farmacologia , Cromatografia Líquida de Alta Pressão , Cinamatos/farmacologia , Depsídeos/farmacologia , Regulação para Baixo/efeitos dos fármacos , Células Hep G2 , Humanos , Chumbo/toxicidade , Peróxidos Lipídicos/análise , Peróxidos Lipídicos/metabolismo , Espectrometria de Massas , NAD(P)H Desidrogenase (Quinona)/genética , NAD(P)H Desidrogenase (Quinona)/metabolismo , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo
13.
Chem Biol Interact ; 314: 108848, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31610156

RESUMO

Cardiomyocyte injury induced by acute myocardial infarction contributes to myocardial dysfunction. Accumulating evidence has demonstrated that pleckstrin homology domain leucine-rich repeat protein phosphatase 2 (PHLPP2) is a cytoprotective protein that protects against various adverse injuries. However, whether PHLPP2 participates in regulating myocardial-infarction-induced cardiomyocyte injury remains unknown. In the present study, we aimed to investigate the biological role and molecular mechanism of PHLPP2 in regulating hypoxia-induced cardiomyocyte injury. Cardiomyocytes were cultured in an anaerobic chamber for 24 h to induce hypoxic injury in vitro. The expression of PHLPP2 was determined by real-time quantitative PCR and Western blot analysis. Cell viability was measured by MTT assay. Cell apoptosis was assessed by TUNEL and caspase-3 activity assays. Intracellular reactive oxygen species (ROS) levels were measured by DCFH-DA probe. PHLPP2 expression was highly upregulated in hypoxia-injured cardiomyocytes. Inhibition of PHLPP2 by small interfering RNA (siRNA)-mediated gene silencing significantly improved the viability of hypoxia-injured cardiomyocytes and attenuated hypoxia-induced apoptosis and ROS production. In contrast, PHLPP2 overexpression exacerbated hypoxia-induced apoptosis and ROS production in cardiomyocytes. Mechanism research revealed that PHLPP2 silencing increased the phosphorylation of glycogen synthase kinase (GSK)-3ß and promoted the nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2). In addition, PHLPP2 inhibition promoted Nrf2/antioxidant response element (ARE) transcriptional activity. However, Nrf2 silencing markedly reversed PHLPP2-inhibition-mediated cardioprotection, while GSK-3ß inhibition partially blocked the PHLPP2-overexpression-induced adverse effect. Taken together, these findings demonstrate that PHLPP2 inhibition alleviates hypoxia-induced cardiomyocyte injury by reinforcing Nrf2/ARE antioxidant signaling via inactivating GSK-3ß, a pathway that highlights the importance of the PHLPP2/GSK-3ß/Nrf2/ARE signaling axis in regulation of cardiomyocyte injury. Our study suggests a potential relevance for PHLPP2 in acute myocardial infarction, and this protein may serve as a promising target for cardioprotection.


Assuntos
Elementos de Resposta Antioxidante/genética , Hipóxia Celular , Fator 2 Relacionado a NF-E2/metabolismo , Fosfoproteínas Fosfatases/metabolismo , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular , Regulação para Baixo , Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Glicogênio Sintase Quinase 3 beta/metabolismo , Camundongos , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Fator 2 Relacionado a NF-E2/genética , Fosfoproteínas Fosfatases/antagonistas & inibidores , Fosfoproteínas Fosfatases/genética , Fosforilação , Pirimidinas/farmacologia , Pirróis/farmacologia , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
14.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(4): 529-535, 2019 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-31484617

RESUMO

To investigate the effect of N-acetylcysteine(NAC)on cognitive function and nuclear factor erythroid 2 related factor 2/ heme oxygenase-1(Nrf2/HO-1)pathway in mouse models of postoperative cognitive dysfunction. Methods Fifty-four male C57BL/6J mice(3-4 months old)were randomly divided into control group,surgery group,and surgery+NAC group by block randomization.The intramedullary fixation for left tibial fracture surgery was performed to establish postoperative cognitive dysfunction models.NAC(150 mg/kg)was administered intraperitoneally in group surgery+NAC 30 minutes before and 3 hours,6 hours after surgery,while saline was given in control group and surgery group.Six mice in each group were selected randomly underwent Morris water maze test on the third day after surgery.Animals were sacrificed at the first and third postoperative days,and the hippocampus was harvested.Enzyme-linked immunosorbent assay was used to quantify the levels of interleukin-6(IL-6)and malondialdehyde(MDA)in hippocampus.Western blot and real-time polymerase chain reaction were used to measure the expressions of Nrf2 and HO-1 in hippocampus. Results There was no significant difference in swimming speed among three groups(F=2.135,P=0.114).Compared with control group and surgery+NAC group,the surgery group had prolonged escape latency(P<0.01),reduced platform crossing times(P<0.01),and shortened time spent in the target quadrant(P<0.01).Compared with the control group,the surgery group and the surgery+NAC group had significantly increased levels of IL-6 and MDA in hippocampus at the first postoperative day(all P=0.000).On the third postoperative day,there was no significant difference in the levels of IL-6(P=0.251)and MDA(P=0.103)between control group and surgery+NAC group.The protein expressions of Nrf2 and HO-1 in hippocampus were significantly higher in surgery group and surgery+NAC group than in control group and significantly higher in surgery+NAC group than in surgery group(all P=0.000).The mRNA expressions of Nrf2 and HO-1 in hippocampus were significantly higher in surgery group and surgery+NAC group than in control group and significantly higher in surgery+NAC group than in surgery group (all P=0.000). Conclusions NAC pretreatment may reduce oxidative stress and inflammatory response in hippocampus and improve cognitive function.Such effect may be relate to the activation of Nrf2/HO-1 pathway.


Assuntos
Acetilcisteína/farmacologia , Cognição/efeitos dos fármacos , Disfunção Cognitiva/tratamento farmacológico , Heme Oxigenase-1/metabolismo , Proteínas de Membrana/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Disfunção Cognitiva/etiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Complicações Pós-Operatórias , Distribuição Aleatória
15.
Toxicol Lett ; 316: 109-118, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31472180

RESUMO

Lithocholic acid (LCA) is both a secondary bile acid and a vitamin D receptor (VDR) ligand. The VDR is activated by 1,25-dihydroxy vitamin D3 and plays an important role in maintaining integrity of the intestinal mucosal barrier. LCA can also substitute for vitamin D to carry out the in vivo functions of vitamin D. However, it is unclear whether activation of the VDR by LCA affects mucosal barrier function. In the present study, we researched the protective effect of LCA on tumor necrosis factor-alpha (TNF-α)-induced intestinal epithelial barrier dysfunction in Caco-2 cells of the human epithelial intestinal adenocarcinoma cell line. Caco-2 cell monolayers were pretreated with LCA and then exposed to 100 ng/mL TNF-α. The results showed that LCA alleviated the decrease in transepithelial electrical resistance and the increase in FITC-Dextran flux induced by TNF-α. LCA ameliorated the TNF-α-induced decrease in protein expression and distribution of ZO-1, E-cadherin, Occludin, and Claudin-1, which are tight junction markers. Additionally, the LCA treatment effectively counteracted TNF-α-mediated downregulation of silent information regulator 1 (SIRT1), nuclear factor erythroid2-related factor 2 (Nrf2), and heme oxygenase-1, which are related to oxidative stress. Increases in NF-κB p-p65 and p-IκB-α induced by TNF-α were significantly inhibited by LCA. Considering all these, the present study indicates that LCA has a significant protective effect on TNF-α-induced injury of intestinal barrier function through the VDR and suggests that suppressing NF-κB signaling and activating the SIRT1/Nrf2 pathway might be one of the mechanisms underlying the protective effect of LCA.


Assuntos
Células Epiteliais/efeitos dos fármacos , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Ácido Litocólico/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Receptores de Calcitriol/agonistas , Sirtuína 1/metabolismo , Fator de Necrose Tumoral alfa/toxicidade , Células CACO-2 , Citoproteção , Impedância Elétrica , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Permeabilidade , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas de Junções Íntimas/metabolismo , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo , Junções Íntimas/patologia
16.
Life Sci ; 236: 116867, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31520598

RESUMO

AIM: Cyclophosphamide (CP) is a potent anticancer and immunosuppressant drug. Studies have shown significant oxidative stress and cognitive impairment but neuroinflammatory and histological aberrations with its administration is underexplored. Nerolidol (NER) is a lipophilic bioactive molecule with antioxidant and anti-inflammatory properties but it has not been explored for neuroprotective potential in CP-induced neurotoxic manifestations. Therefore, in the present study, we aimed to evaluate the neuroprotective potential of NER in CP-induced neuroinflammation and associated comorbid conditions like depression and cognitive dysfunctions. MATERIALS AND METHOD: In-silico study using Schrödinger software was used to assess the binding affinity of NER with Nrf2. In the In vivo study, NER 200 and 400 mg/kg p.o. were given from 1st day to 14th day. CP 200 mg/kg, i.p., was administered on the 7th day. After 24 h of the last dosing, neurobehavioral tests like spontaneous body alternation, passive avoidance and forced swim test were performed. On completion of study, mice were sacrificed, hippocampus and cortex were removed for biochemical estimations, histopathology and immunohistochemistry of p65 NF- κB and Nrf2. KEY FINDINGS: In-silico study showed significant binding of NER into the pocket domain of Nrf2. In-vivo study showed protective effect of NER against CP-induced neuroinflammation, oxidative stress, cognitive impairment and structural abnormalities in the hippocampus and cortex regions. SIGNIFICANCE: Findings of the study suggested that NER is a potential therapeutic molecule which can mitigate CP-induced neurotoxic manifestations via Nrf2 and NF-κB pathway. However, more detailed studies are needed to explicate the mechanism underlying its neuroprotective effect.


Assuntos
Disfunção Cognitiva/prevenção & controle , Ciclofosfamida/toxicidade , Inflamação/prevenção & controle , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Síndromes Neurotóxicas/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Sesquiterpenos/farmacologia , Animais , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Regulação da Expressão Gênica , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Imunossupressores/toxicidade , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Fator 2 Relacionado a NF-E2/genética , NF-kappa B/genética , Fármacos Neuroprotetores , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Transdução de Sinais
17.
Biol Res ; 52(1): 49, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492195

RESUMO

BACKGROUND: Psoriasis is a common and intractable skin disease affecting the physical and mental health of patients. The accumulation of ROS is involved in the pathogenesis of psoriasis and antioxidants are believed to be therapeutic. This study aimed to investigate the therapeutic efficacy of astilbin on ROS accumulation in psoriasis. RESULTS: The study showed that 50 µg/ml astilbin could inhibit the growth and reduce the accumulation of ROS in HaCaT cells stimulated by IL-17 and TNF-α. Astilbin could elevate the Nrf2 accumulation in the nuclei, eventually leading to the transcriptional activation of various antioxidant proteins and reducing the expression of VEGF. CONCLUSIONS: Our results collectively suggest that astilbin could induce Nrf2 nucleus translocation, which is contribute to reduce the ROS accumulation and VEGF expression, and inhibit the proliferation of HaCaT cells.


Assuntos
Flavonóis/administração & dosagem , Queratinócitos/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Psoríase/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Interleucina-17/metabolismo , Queratinócitos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fator 2 Relacionado a NF-E2/metabolismo , Psoríase/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
18.
J Agric Food Chem ; 67(40): 11089-11098, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31509411

RESUMO

Reactive oxygen species and subsequent oxidative stress are reported to play important roles in chronic metabolic diseases. Plant-derived polyphenols, especially food-derived phenolics, have attracted a lot of attention due to their potential usage against oxidative stress-related diseases. The leaf of Psidium guajava (known as guava) is regarded as a good resource of polyphenols and its products are commercially available in Japan as functional foods against multiple chronic metabolism disorders. In the course of finding novel polyphenols with antioxidative activities from guava leaf, 11 acylated phenolic glycosides (1-11), including 5 new oleuropeic acid-conjugated phenolic glycosides, named guajanosides A-E (1, 2, and 5-7), along with 17 known meroterpenoides (12-28), were isolated and identified. Their structures were determined by spectroscopic data analysis, chemical degradation, and acid hydrolysis. Compounds 1, 2, and 5-11 displayed potent reactive oxygen species-scavenging activity in lipopolysaccharide-stimulated RAW 264.7 macrophage cells. Western blot revealed that compound 6 markedly increased the expression levels of nuclear factor-erythroid 2-related factor 2 (Nrf2), NAD(P)H quinone dehydrogenase 1 (NQO1), and the glutamate-cysteine ligase catalytic subunit. The current study revealed the presence of oleuropeic acid-derived phenolic glycosides in guava leaf and highlighted the potential usage of this type of phenolics against oxidative stress-related metabolic diseases via activation of the Nrf2 signaling pathway.


Assuntos
Depuradores de Radicais Livres/farmacologia , Glicosídeos/farmacologia , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Psidium/química , Espécies Reativas de Oxigênio/metabolismo , Animais , Depuradores de Radicais Livres/química , Glicosídeos/química , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fenóis/química , Extratos Vegetais/química , Folhas de Planta/química , Células RAW 264.7
19.
Life Sci ; 235: 116863, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31513817

RESUMO

AIMS: To determine whether dimethyl fumarate (DMF) can protect against lipopolysaccharide (LPS) -induced myocardial injury. MAIN METHODS: H9c2 cells pretreated with or without DMF were stimulated with LPS. Cell viability and apoptosis were evaluated. Nrf2 and HO-1 expression were detected using Western blotting. Mitochondrial morphology, mitochondrial superoxide production were observed using confocal microscope. Mitochondrial respiration function was measured using Seahorse bioanalyzer. KEY FINDINGS: (1) The cell viability decreased, LDH release and apoptosis increased in LPS- challenged H9c2 cells. DMF pretreatment brought a higher cell viability, and a lower LDH leakage and apoptosis than those of LPS group (P < 0.01). (2) DMF pretreatment resulted in an increased Nrf2 and HO-1 expression, and enhanced nuclear Nrf2 level in LPS-challenged cells (P < 0.01). (3) Nrf2-siRNA could inhibit DMF-induced enhancement of HO-1 expression and cell viability, and partly abolish DMF-induced reduction of LDH leakage and apoptosis. (4) ERK1/2 inhibitor PD98059 could not only prevent the DMF-induced enhancement of nuclear Nrf2 and HO-1, but also inhibit DMF-induced increase in cell viability. (5) Compared with LPS-challenged cells, DMF pretreatment caused a lower production of mitochondrial superoxide and a higher mitochondrial membrane potential, which could be abolished by Nrf2-siRNA. (6) DMF could attenuate LPS-induced mitochondrial fragmentation and improve mitochondrial respiration function by enhancement of the oxygen consumption rate of basal respiration and ATP production in LPS-challenged cells (P < 0.01). SIGNIFICANCE: DMF protects cardiomyocytes against LPS-induced damage. ERK1/2-dependent activation of Nrf2/HO-1 pathway is responsible for DMF-induced cardioprotection via reduction of oxidative stress, improvement of mitochondrial morphology and energy metabolism.


Assuntos
Fumarato de Dimetilo/farmacologia , Mitocôndrias/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Trifosfato de Adenosina/biossíntese , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Fumarato de Dimetilo/antagonistas & inibidores , Flavonoides/farmacologia , Heme Oxigenase-1/metabolismo , Humanos , L-Lactato Desidrogenase/metabolismo , Lipopolissacarídeos/efeitos adversos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Miócitos Cardíacos/metabolismo , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Consumo de Oxigênio/efeitos dos fármacos , Substâncias Protetoras/farmacologia , RNA Interferente Pequeno/farmacologia , Superóxidos/metabolismo
20.
Adv Exp Med Biol ; 1155: 567-581, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468432

RESUMO

Here, we investigated the hepatoprotective effect of a hot water extract from Loliolus beka gray meat (LBMH) containing plentiful taurine in H2O2-induced oxidative stress in hepatocytes. LBMH potently scavenged the 2,2-azino-bis(3-ethylbenzthiazoline)-6-sulfonic acid (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals and exhibited the good reducing power and the oxygen radical absorbance capacity (ORAC) value. Also, LBMH improved the cell viability against H2O2-induced hepatic damage in cultured hepatocytes by reducing intracellular reactive oxygen species (ROS) production. In addition, LBMH inhibited apoptosis via a reduction in sub-G1 cell population, as well as inhibition of apoptotic body formation from H2O2-induced oxidative damage in hepatocytes. Moreover, LBMH regulated the expression levels of Bax, a pro-apoptotic molecule and Bcl-2, an anti-apoptotic molecule in H2O2-treated hepatocytes. Additionally, pre-treatment with LBMH increased the expression of heme oxygenase 1 (HO-1), which is a hepatoprotective enzyme, by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) in H2O2-treated hepatocytes. Taken together, LBMH may be useful as a food ingredient for treatment of liver disease by regulating the Nrf2/HO-1 signal pathway.


Assuntos
Antioxidantes , Extratos Celulares/farmacologia , Decapodiformes/química , Hepatócitos/efeitos dos fármacos , Estresse Oxidativo , Taurina/farmacologia , Animais , Células Cultivadas , Heme Oxigenase-1/metabolismo , Hepatócitos/citologia , Humanos , Peróxido de Hidrogênio , Carne , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo
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