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1.
Acta Cir Bras ; 34(7): e201900706, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31531540

RESUMO

PURPOSE: To investigate the protective roles of pyracantha fortune fruit extract (PFE) on acute renal toxicity induced by cadmium chloride (CdCl2) in rats. METHODS: Rats were pretreated with PFE and consecutively injected with CdCl2 (6.5 mg/kg) for 5 days. RESULTS: The concentration of Cd, kidney weight, malondialdehyde (MDA), and nitric oxide (NO) production were remarkably increased in CdCl2 group as well as the levels of plasma uric acid, urea, and creatinine (P < 0.001). However, the body weight and glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione peroxidase (GR) levels were markedly reduced by CdCl2 treatment (P < 0.001). Histological manifestations of renal tissue showed severely adverse changes. Moreover, CdCl2 treatment significantly decreased the B-cell lymphoma-2 (Bcl-2) expression while increased the Bcl-2-Associated X Protein (Bax), tumor necrosis factor-α (TNF-α) expression (P < 0.001). Additionally, the expression of Nrf2/Keap 1 related proteins Keap-1 gained a significant increase (P < 0.001), whereas the Nrf2, HO-1, γ-GCS, GSH-Px and NQO1 expression decreased by CdCl2 treatment (P < 0.05). These rats were pretreated with PFE to improve the changes caused by CdCl2 treatment. CONCLUSION: PFE could protect the kidney against acute renal toxicity induced by CdCl2.


Assuntos
Antioxidantes/farmacologia , Cloreto de Cádmio/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Rim/efeitos dos fármacos , Extratos Vegetais/farmacologia , Pyracantha/química , Animais , Catalase/metabolismo , Modelos Animais de Doenças , Frutas/química , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Rim/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Superóxido Dismutase/metabolismo
2.
Life Sci ; 234: 116780, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31430453

RESUMO

Bronchial asthma and obesity are common health problems. Obesity is already responsible for 300,000 deaths per year. AIMS: The aim of the present study was to assess whether apocynin, alpha lipoic acid and probiotic administration in combination with low-fat diet supplementation influences the levels of antioxidant enzymes in the pulmonary tissues of obese asthmatic mice. MAIN METHODS: The study was performed on male C57/BL6 mice divided into 10 groups: (I) control; (II) asthma; (III) obesity; (IV) asthma + obesity; (V) asthma + obesity + apocynin p.o. 15 mg/kg/day for 12 weeks; (VI) asthma + obesity + low-fat diet for 12 weeks; (VII) asthma + obesity + low-fat diet for 12 weeks with apocynin p.o. 15 mg/kg/day; (VIII) asthma + obesity + low-fat diet with probiotics for 12 weeks; (IX) asthma + obesity + low-fat diet for 12 weeks with lipoic acid p.o. 100 mg/kg/day for 12 weeks; (X) asthma + obesity + standard diet with probiotics for 12 weeks. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) activity were examined. The administration of apocynin alone and apocynin in combination with a low-fat diet resulted in a significant increase in SOD values (respectively p < 0.001; p = 0.010). Application of probiotics resulted in a decrease in CAT activity (p = 0.037) and an increase in GPx activity (p < 0.001) compared to obese asthmatic mice. The administration of lipoic acid resulted in an increase in GR activity (p = 0.024 vs. control). KEY FINDINGS: Supplementation containing apocynin, lipoic acid and probiotics has a positive influence on the antioxidant capacity of the pulmonary tissues of obese asthmatic mice. SIGNIFICANCE: These results may contribute to the development of new therapeutic approaches.


Assuntos
Acetofenonas/uso terapêutico , Antioxidantes/uso terapêutico , Asma/tratamento farmacológico , Obesidade/tratamento farmacológico , Probióticos/uso terapêutico , Ácido Tióctico/uso terapêutico , Animais , Asma/complicações , Asma/metabolismo , Catalase/análise , Catalase/metabolismo , Glutationa Peroxidase/análise , Glutationa Peroxidase/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/complicações , Obesidade/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/análise , Superóxido Dismutase/metabolismo
3.
Adv Exp Med Biol ; 1155: 185-196, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468397

RESUMO

In the present study, we evaluated the antioxidant and anti-stress activities of taurine in electric foot-shock stress model rats. Taurine supplementation markedly increased the hepatic glutathione (GSH) levels, compared to the levels in the stress group. In addition, activities of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) were improved in the taurine-treated group. Plasma cortisol and dehydroepiandrosterone-sulfate (DHEA-S) levels were significantly reduced in the taurine-supplemented group compared to those in the stress group. In contrast, the levels of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were markedly increased in the taurine or betaine-treated group compared to those in the stress group. It may be concluded that taurine produces beneficial effects in the form of antioxidant status and biochemical alterations in foot-shock-induced acute stress in rats.


Assuntos
Antioxidantes/farmacologia , Fígado/efeitos dos fármacos , Estresse Fisiológico , Taurina/farmacologia , Animais , Catalase/metabolismo , Sulfato de Desidroepiandrosterona/sangue , Estimulação Elétrica , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Transferase/metabolismo , Hidrocortisona/sangue , Ácido Hidroxi-Indolacético/sangue , Fígado/metabolismo , Estresse Oxidativo , Ratos , Ratos Wistar , Serotonina/sangue
4.
Adv Exp Med Biol ; 1155: 739-746, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468444

RESUMO

The herbicide Paraquat induce oxidative stress-mediated lung injury. Taurine is a well-known antioxidant. This study was designed to explore the effect of taurine on paraquat-induced injury and its related mechanism in A549 cells. The cells were pretreated with various concentrations of taurine for 30 min prior to paraquat exposure. 24 h later, cell viability was examined by the MTT assay. The level of glutathione (GSH) and the activity of glutathione peroxidase (GPx) were analyzed. The results show that taurine treatment significantly attenuates the decrease in cell viability mediated by paraquat in A549 cells. Taurine also reversed paraquat-induced disturbances in GSH content and GPx activity. Taurine exerts protection against paraquat-mediated A549 cell toxicity likely through modulation of oxidative stress.


Assuntos
Células Epiteliais/efeitos dos fármacos , Estresse Oxidativo , Paraquat/toxicidade , Taurina/farmacologia , Células A549 , Células Cultivadas , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Humanos , Pulmão/citologia
5.
Exp Parasitol ; 205: 107747, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31442454

RESUMO

Development of new chemotherapeutic agents is an essential issue in the treatment and control of a disease. This study aimed to evaluate the anti-leishmanial activity of amiodarone, an antiarrhythmic class III drug, against Leishmania major, the most prevalent etiological agent of cutaneous leishmaniasis in the old world. The proliferation of promastigotes and intracellular amastigotes in the absence or presence of amiodarone was estimated, in an in vitro study. For in vivo study, five weeks after infection of BALB/c mice with L. major, when the lesions appeared at the injection site, the mice were divided into four groups (n = 6 each); treatment was conducted for 28 consecutive days with vehicle, amiodarone at 40 mg/kg orally and glucantime at 60 mg/kg intraperitoneally. Therapy with amiodarone reduced the size of lesions compared to the untreated group after 12 days. Amiodarone decreased the parasite load and inflammatory responses, particularly the macrophages containing amastigotes, and enhanced granulation tissue formation in the dermis and subcutaneous area. The Tumor necrosis factor-α and Interleukin-6 levels were significantly lower in the cell culture supernatants of the inguinal lymph node in the amiodarone treated group compared to the vehicle and untreated groups. Amiodarone significantly increased the activity of glutathione peroxidase in comparison to the vehicle and untreated groups but did not affect the plasma levels of superoxide dismutase, malondialdehyde, adiponectin, and ferric reducing ability of plasma. Therefore, the anti- L. major activity and immunomodulatory effects of amiodarone reduced the parasitic load and enhanced wound healing in cutaneous leishmaniasis in BALB/c mice. Amiodarone reduced the lesion surface area, but it did not cure it completely.


Assuntos
Amiodarona/uso terapêutico , Antiprotozoários/uso terapêutico , Leishmania major/efeitos dos fármacos , Leishmaniose Cutânea/tratamento farmacológico , Adiponectina/sangue , Amiodarona/farmacologia , Animais , Antiarrítmicos/farmacologia , Antiarrítmicos/uso terapêutico , Antiprotozoários/farmacologia , Linhagem Celular , Feminino , Glutationa Peroxidase/metabolismo , Concentração Inibidora 50 , Interleucina-6/análise , Leishmania major/ultraestrutura , Leishmaniose Cutânea/parasitologia , Linfonodos/química , Linfonodos/imunologia , Macrófagos/parasitologia , Malondialdeído/sangue , Antimoniato de Meglumina/farmacologia , Antimoniato de Meglumina/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Carga Parasitária , Distribuição Aleatória , Pele/parasitologia , Pele/patologia , Pele/ultraestrutura , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/análise
6.
Cancer Sci ; 110(10): 3173-3182, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31464035

RESUMO

Ferroptosis is an iron-dependent, lipid peroxide-driven cell death caused by inhibition of the cystine/glutamate transporter, which is of importance for the survival of triple-negative breast cancer (TNBC) cells. Erastin is a low molecular weight chemotherapy drug that induces ferroptosis; however, poor water solubility and renal toxicity have limited its application. Exosomes, as drug delivery vehicles with low immunogenicity, high biocompatibility and high efficiency, have attracted increasing attention in recent years. Herein, we developed a formulation of erastin-loaded exosomes labeled with folate (FA) to form FA-vectorized exosomes loaded with erastin (erastin@FA-exo) to target TNBC cells with overexpression of FA receptors. The characterization, drug release, internalization and anti-tumor effect in vitro of erastin@FA-exo were determined. Erastin@FA-exo could increase the uptake efficiency of erastin into MDA-MB-231 cells; compared with erastin@exo and free erastin, erastin@FA-exo has a better inhibitory effect on the proliferation and migration of MDA-MB-231 cells. Furthermore, erastin@FA-exo promoted ferroptosis with intracellular depletion of glutathione and reactive oxygen species overgeneration. Western blot analyses revealed that erastin@FA-exo suppressed expression of glutathione peroxidase 4 (GPX4) and upregulated expression of cysteine dioxygenase (CDO1). We conclude that targeting and biocompatibility of exosome-based erastin preparations provide an innovative and powerful delivery platform for anti-cancer therapy.


Assuntos
Exossomos/química , Ácido Fólico/química , Piperazinas/farmacologia , Neoplasias de Mama Triplo Negativas/metabolismo , Morte Celular , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cisteína Dioxigenase/metabolismo , Sistemas de Liberação de Medicamentos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , Humanos , Piperazinas/química , Espécies Reativas de Oxigênio/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
7.
Life Sci ; 232: 116677, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31340166

RESUMO

AIMS: Senescence is a state ensuing aging to eliminate age-associated damage with an irreversible cell-cycle arrest mechanism, which is historically believed to be one of the tumor responses to therapy. Doxorubicin as an anti-cancer drug has been used in cancer treatment for a long time. Liposomal doxorubicin (Ldox) is a liposomal formulation of doxorubicin, which increases the doxorubicin permanency. The aim of this study was to examine the toxicity of these two formulations by comparing them in terms of their ability to induce cellular senescence. MAIN METHODS: The study groups included a control group, three DOX (0.75, 0.5, 0.1 mg/kg/BW) and three Ldox groups (0.1, 0.05, 0.025 mg/kg/BW). Heart tissues were studied regarding oxidative stress assessment, mitochondrial function, inflammatory markers and biochemical and histopathological evaluation. Real-Time PCR was used for P53 and SA ß-gal expression. KEY FINDINGS: Based on the results, the highest doses of Dox and Ldox (0.75 and 0.1 mg/kg/BW respectively) significantly increased the level of inflammatory markers and according to other factors especially p53 and SA ß-gal expression, both were able to induce senescence but the changes in Ldox were less tangible than the Dox.


Assuntos
Senescência Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , NF-kappa B/metabolismo , Animais , Biomarcadores/metabolismo , Doxorrubicina/análogos & derivados , Glutationa Peroxidase/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Miocárdio/patologia , Estresse Oxidativo/efeitos dos fármacos , Polietilenoglicóis/farmacologia , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Proteína Supressora de Tumor p53/metabolismo
8.
Life Sci ; 231: 116550, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31185235

RESUMO

AIM: Acrylamide (AA) is a common heat-generated toxicant in some food. Inhibiting its formation with natural antioxidants is of great significance. The current study aims to investigate the alleviative effect and the underlying mechanism of allicin against AA-induced oxidative stress in BRL-3A cells. MAIN METHODS: BRL-3A cells were pretreated with allicin at different concentrations for 2 h, followed by AA treatment. Cell viability was determined by Cell Counting kit-8 (CCK-8). Intracellular reactive oxygen species (ROS) status was measured using the 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) method. Levels of oxidative stress markers were determined by measuring total superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and 8-hydroxy-desoxyguanosine (8-OHdG) using commercial kits. Expression of the mitogen-activated protein kinase (MAPK) pathway-related proteins was determined by Western blotting. KEY FINDINGS: Allicin markedly mitigated oxidative and DNA damage by increasing the activities of SOD and GSH-Px and decreasing the levels of ROS and 8-OHdG. Concomitant with these biochemical parameters, pretreatment with allicin reversed the impact of AA on the expression of p-JNK, p-ERK1/2 and p-p38. Allicin combined with SP600125 (JNK inhibitor) and SB202190 (p38 inhibitor) enhanced cell viability in the presence of AA, as opposed to SCH772984 (ERK inhibitor). Notably, allicin ameliorated the expression of KGF, Gadd45a, c-Fos, Dusp5 and Phospholipase A2, which were related to liver injury. SIGNIFICANCE: Collectively, these findings demonstrate that allicin exerts protective effects against AA-induced oxidative stress by modulating the MAPK signaling pathway in BRL-3A cells.


Assuntos
Estresse Oxidativo/efeitos dos fármacos , Ácidos Sulfínicos/farmacologia , Acrilamida/farmacologia , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
9.
Environ Sci Pollut Res Int ; 26(23): 23442-23452, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31197674

RESUMO

The current study demonstrates oxidative damage and associated neurotoxicity following pH stress in two freshwater carp Labeo rohita and Cirrhinus cirrhosus. Carp (n = 6, 3 replicates) were exposed to four different pH (5.5, 6, 7.5, and 8) against control (pH 6.8 ± 0.05) for 7 days. After completion of treatment, levels of enzymatic (superoxide dismutase [SOD], catalase [CAT], glutathione reductase [GRd]) and non-enzymatic antioxidants (malondialdehyde [MDA], glutathione [GSH]), brain neurological parameters (Na+-K+ATPase, acetylcholinesterase [AcHE], monoamine oxidase [MAO], and nitric oxide [NO]), xanthine oxidase (XO), heat shock proteins (HSP70 and HSP90), and transcription factor NFkB were measured in carp brain. Variation in the pH caused a significant alteration in the glutathione system (glutathione and glutathione reductase), SOD-CAT system, and stress marker malondialdehyde (MDA). Xanthine oxidase was also induced significantly after pH exposure. Brain neurological parameters (MAO, NO, AChE, and Na+-K+ATPase) were significantly reduced at each pH-treated carp group though inhibition was highest at lower acidic pH (5.5). Cirrhinus cirrhosus was more affected than that of Labeo rohita. Molecular chaperon HSP70 expression was induced in all pH-treated groups though such induction was more in acid-stressed fish. HSP90 was found to increase only in acid-stressed carp brain. Expression of NFkB was elevated significantly at each treatment group except for pH 7.5. Finally, both acidic and alkaline pH in the aquatic system was found to disturb oxidative balance in carp brain which ultimately affects the neurological activity in carp. However, acidic environment in the aquatic system was more detrimental than the alkaline system regarding oxidative damage and subsequent neurotoxicity in carp brain.


Assuntos
Encéfalo/metabolismo , Peixes/fisiologia , Estresse Fisiológico/fisiologia , Poluentes Químicos da Água/toxicidade , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Carpas/metabolismo , Catalase/metabolismo , Cyprinidae/metabolismo , Água Doce , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Malondialdeído/metabolismo , Oxirredução , Estresse Oxidativo , Alimentos Marinhos , ATPase Trocadora de Sódio-Potássio/metabolismo , Superóxido Dismutase/metabolismo , Xantina Oxidase/metabolismo
10.
J Sci Food Agric ; 99(13): 6097-6107, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31250448

RESUMO

BACKGROUND: Reactive oxygen species (ROS) can cause DNA damage. Rice protein (RP) inhibits ROS accumulation. However, a link between the reduction of ROS-derived DNA damage and the intake of RP is far from clear. The main objective of this study is to elucidate the effects of RPs on the reduction of DNA damage in growing and adult rats. RESULTS: An intake of RP for 2 weeks significantly reduced the hepatic accumulation of ROS and 8-hydroxydeoxyguanosine (8-OHdG) in growing and adult rats, whereas the hepatic p53 content was markedly increased by RPs. After 2 weeks' feeding, the mRNA levels and protein expressions of p53, ataxia-telangiectasia mutated (ATM), and Checkpoint kinase 2 (Chk2) were up-regulated by RPs, whereas Murine Double Minute 2 (MDM2) expressions were markedly inhibited by RPs, resulting in more p53 being translocated into the nucleus. Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) was activated by RP by reducing Kelch-like ECH-associated protein 1 (Keap1), resulting in the up-regulation of antioxidant expressions of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in RP groups. CONCLUSION: Rice protein can exert an endogenous antioxidant activity to reduce ROS-derived DNA damage by activating the Nrf2-Keap1 pathway. This study suggests that the activation of the ATM-Chk2-p53 pathway might be one of the mechanisms exerted by RP for reducing DNA damage in growing and adult rats. © 2019 Society of Chemical Industry.


Assuntos
Antioxidantes/metabolismo , Dano ao DNA , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Catalase/genética , Catalase/metabolismo , Quinase do Ponto de Checagem 2/genética , Quinase do Ponto de Checagem 2/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fígado/metabolismo , Masculino , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Proteína Supressora de Tumor p53/genética
11.
Life Sci ; 231: 116572, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31207309

RESUMO

OBJECTIVES: The aim of this study was to investigate whether some of the cephalosporin group antibiotics have inhibition effects on GR and GST enzymes with important functions in the metabolic pathway. METHODS: In this study, some selected cephalosporin group antibiotics on GST and GR enzyme was carried out using 96 rats. 16 groups (16 × 6) were created from these rats, divided to another 4 groups (4 × 24). The resulting groups were named as sham groups, cefazolin groups, cefuroxime groups and cefoperazone groups, respectively. The antibiotics used were injected to cefazolin, cefuroxime and cefoperazone groups. The inhibition effects of the antibiotics were measured in the different time intervals (1st, 3th, 5th, 7th). The statistical investigation of the results was performed using the SPSS software program. RESULTS: Results revealed the complex effects of the tested substances on GR and GST activity at different time intervals and in different tissues (p < 0.05). This indicated that the tested substances could be exposed to different interactions in vivo. CONCLUSION: The tested antibiotics showed some significant inhibition effects on the GST and GR enzyme activity in some tissues of brain, eye and muscle. The interaction of enzyme - the drug is a key factor to highlight the toxicological mechanism. For this reason, the results obtained from in vivo experiments are crucial to explane the physiological properties of the enzymes.


Assuntos
Cefalosporinas/farmacologia , Glutationa Redutase/antagonistas & inibidores , Glutationa Transferase/antagonistas & inibidores , Animais , Antibacterianos/farmacologia , Cefazolina/farmacologia , Cefoperazona/farmacologia , Cefuroxima/farmacologia , Inibidores Enzimáticos/farmacologia , Glutationa/metabolismo , Glutationa Peroxidase/antagonistas & inibidores , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Glutationa Transferase/metabolismo , Ratos
12.
Life Sci ; 232: 116595, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31238053

RESUMO

AIMS: The world's population is becoming aged and the proportion of older persons is growing in almost every country in the world. Ellagic acid (EA) shows abundant pharmacological properties. Therefore, we aimed to determine the mechanism of anti-aging effects of low and high doses of EA. MAIN METHODS: Aging model was induced by d-galactose (DG), and the anti-aging effect of EA alone or in the presence of PPAR-γ antagonist GW9662, and in combination with metformin were evaluated. The activities of ALT, AST, and AChE, the levels of FBS, HbA1c, testosterone and DHEA-SO4, MDA, GSH, TNF-α, IL-6, advanced glycation end products (AGEs), and BDNF were measured in serum, liver or brain. KEY FINDINGS: DG led to increasing in the levels of IL-6, TNF-α, MDA, AChE, AGEs, ALT, AST, FBS, and HbA1c, in which decrease in the levels of body weight, GSH, BDNF, DHEA-SO4 and testosterone. Metformin (300 mg/kg) abrogated the effects of DG-induced aging model. We also found that the low dose of EA (30 mg/kg) decreases the deteriorative effects of DG-induced aging at 10 weeks of treatment only, however, high dose of EA (100 mg/kg) was effective at both 6 and 10 weeks of treatment. The addition of GW9662 completely reversed the effects of the low dose of EA, but not for the high dose, on DG-induced aging model. SIGNIFICANCE: We revealed that daily and oral administration of EA provides anti-aging effects at low dose in a PPAR-γ receptor-dependent fashion, but not at the high dose.


Assuntos
Envelhecimento/efeitos dos fármacos , Ácido Elágico/farmacologia , PPAR gama/metabolismo , Envelhecimento/fisiologia , Anilidas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Encéfalo/metabolismo , Galactose/farmacologia , Glutationa Peroxidase/metabolismo , Fígado/metabolismo , Masculino , Malondialdeído/metabolismo , Metformina/farmacologia , Camundongos , Modelos Animais , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
13.
Environ Sci Pollut Res Int ; 26(22): 22562-22574, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31165450

RESUMO

Zingerone (ZO), one of the active components of ginger (Zingiber officinale), is a phenolic alkanone with antioxidant, antiapoptotic, and anti-inflammatory properties. Cisplatin (CP) is a widely used chemotherapeutic drug for solid tumors, but its therapeutic use is limited due to dose-dependent nephrotoxicity. In the present study, we investigated the ameliorative effect of ZO against CP-induced nephrotoxicity. Intraperitoneal administration of single-dose CP (7 mg/kg body weight) on the first day enhanced kidney lipid peroxidation and reduced antioxidant enzyme activities such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione (GSH). CP increased serum urea and creatinine levels and disrupted histological integrity while causing a decrease aquaporin 1 (AQP1) level in the kidney tissues. CP induced inflammatory responses by elevating the levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-33 (IL-33) and nuclear factor kappa B (NF-κB), and activities of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, it also caused oxidative DNA damage and activation of apoptotic pathway by increasing of 8-hydroxy-2'-deoxyguanosine (8-OHdG), p53, cysteine aspartate-specific protease-3 (caspase-3), and Bcl-2-associated x protein (bax) while decreasing B cell lymphoma-2 (Bcl-2). However, treatment with ZO at a dose of 25 and 50 mg/kg b.wt. for 7 days significantly decreased oxidative stress, apoptosis, inflammation, and histopathological alterations while increased AQP1 levels in the kidney tissue. The results of the current study suggested that ZO as an effective natural product attenuates CP-induced nephrotoxicity.


Assuntos
Antioxidantes/metabolismo , Cisplatino/toxicidade , Guaiacol/análogos & derivados , Rim/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Autofagia , Nitrogênio da Ureia Sanguínea , Catalase/metabolismo , Dano ao DNA , Desoxiguanosina/análogos & derivados , Feminino , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Guaiacol/metabolismo , Inflamação/metabolismo , Interleucina-6/metabolismo , Rim/metabolismo , Peroxidação de Lipídeos , Masculino , NF-kappa B/metabolismo , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Ratos , Superóxido Dismutase/metabolismo , Testes de Toxicidade , Fator de Necrose Tumoral alfa/metabolismo
14.
Environ Sci Pollut Res Int ; 26(22): 22736-22746, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31172438

RESUMO

The Thymus vulgaris (T. vulgaris) has been used in foods for the flavor, aroma, and preservation and in folk medicines. The objective of the present work was to determine the antioxidant and protective effects of T. vulgaris extract against lead (Pb)-intoxicated rats. A thirty-two male Sprague-Dawley were randomly assigned into 4 equal groups and treated for six weeks as follows: group I (GP-I), served as negative control; GP-II, -III, and -IV received either Pb acetate in drinking water (500 mg/L), T. vulgaris extract (500 mg/kg/day) by oral gavage or Pb acetate with T. vulgaris extract, respectively. Blood samples were collected at the end of the study week 6 to measure the hepatic and renal biochemical markers, complete blood count alongside the serum levels of interleukin (IL)-1ß, IL-6, IL-10, tumor necrosis (TNF)-α, and interferon (IFN)-γ. Additionally, liver and kidney tissue specimens were collected for histopathology as well as to measure the antioxidant-reduced glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) alongside the lipid peroxidation marker, malonaldehyde (MDA). The results indicated that Pb toxicity increased the serum levels of IL-1ß, IL-6, and TNF-α, whereas IL-10 and IFN-γ were reduced. The results showed disturbed liver and renal functions; increased serum levels of ALT, AST, ALP, total bilirubin, creatinine, and urea; and decreased total protein, albumin, and calcium. The GSH, Gpx, and CAT levels were significantly decreased in the Pb-administrated group, while MDA was increased. However, regarding the hepatorenal markers, those animals treated with T. vulgaris alone did not induce any significant changes. Moreover, the combined treatment with T. vulgaris extract together with Pb showed significant improvement in Pb-induced toxicity in all the tested parameters compared to the negative control group. We investigated the potential protective effects of the medicinal plant T. vulgaris in vivo, since there are no publications that address the potential protective effect of this leaf extract against Pb-induced hepatorenal toxicity. Our studies concluded that the T. vulgaris extract reduces Pb overload in hepatorenal tissues, and that this has a potential immunomodulatory role, antioxidant activity, and a protective effect against Pb toxicity.


Assuntos
Antioxidantes/metabolismo , Chumbo/toxicidade , Extratos Vegetais/metabolismo , Thymus (Planta) , Animais , Catalase/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Interleucina-10 , Rim/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo
15.
J Photochem Photobiol B ; 197: 111538, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31247385

RESUMO

The effects of topically administered snake (Deinagkistrodon acutus) oil and its main fatty acid components on skin photodamage were explored. Epidermal thickness, mice body weight, antioxidant enzymes (superoxide dismutase, glutathione peroxidase, catalase), inflammatory cytokines (tumor necrosis factor alpha and interleukin-6), skin histology, collagen content, and metalloproteinase-1 indicators were analyzed. The results show that topical application of both snake oil and its main fatty acids recovered ultraviolet B (UVB) irradiation induced antioxidant enzymes depletion, prevented metalloproteinase-1. Snake oil and its main fatty acids suppressed dermal infiltration of inflammatory cells and reduced inflammatory cytokines levels. Notably, there was no significant difference in the antioxidant activity but a significant difference in the anti-inflammatory activity between fatty acids and snake oil under the same dose. Finally, snake oil and its main fatty acids inhibited UVB-induced histological damage such as epidermal thickening, collagen fiber and elastic fiber destruction. Our study demonstrated for the first time in KM mice that snake oil exhibited prominent photoprotection activity by protecting the activity of antioxidant enzymes and inhibiting inflammatory factors, as well as reducing the generation of MMP-1. What's more, the main fatty acids in snake oil play an important role in preventing photo-damage especially in protecting antioxidant enzyme activity.


Assuntos
Anti-Inflamatórios/farmacologia , Ácidos Graxos/farmacologia , Óleos Voláteis/química , Pele/efeitos dos fármacos , Serpentes/metabolismo , Raios Ultravioleta , Animais , Anti-Inflamatórios/química , Antioxidantes/metabolismo , Catalase/metabolismo , Citocinas/metabolismo , Epiderme/fisiologia , Ácidos Graxos/química , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Glutationa Peroxidase/metabolismo , Hidroxiprolina/análise , Interleucina-6/genética , Interleucina-6/metabolismo , Metaloproteinase 1 da Matriz/metabolismo , Camundongos , Pele/metabolismo , Pele/patologia , Pele/efeitos da radiação , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
16.
Food Chem Toxicol ; 131: 110545, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31163222

RESUMO

This investigation explored a dietary therapy of pectic polysaccharide (CCPS) (2 mg/ Kg BW) against female repro-toxicity and infertility triggered by sodium arsenite (As3+) (10 mg/ Kg BW) in Wistar rats. The isolated CCPS consists of D-galactose and D-methyl galacturonate with a molar ratio of 1: 4. FTIR spectral analysis of CCPS and CCPS- sodium arsenite (As3+) complex indicated a possible chelating property of CCPS in presence of binding sites (OH-/COOH) for As3+. Series of negatively charged galacturonate residues in CCPS provide better potential for cation chelation. CCPS significantly mitigated As3+ induced ovarian, uterine lipid peroxidation, and reactive oxygen species (ROS) generation by the restoration of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) activities. CCPS post-treatment enhanced ovarian steroidogenesis along with a restoration of normal tissue histoarchitecture in As3+ fed rats by regulating the estradiol receptor alpha (ER-α). CCPS suppressed anti-inflammatory properties effectively found since a down-regulation of NF-kappa B (NF-қB), pro-inflammatory tumor necrosis-α (TNF-α) and interleukin-6 (IL-6) were observed in arsenicated rats with CCPS. This study confirmed the up-regulation of uterine pro-apoptotic/ apoptotic proteins caspase-3, poly ADP ribose polymerase (PARP), proliferating cell nuclear antigen (PCNA), phospho p53 and Bax, followed by down-regulation of Bcl-2 and protein Kinase B (AKT) signaling pathway along with uterine tissue regeneration in As3+ exposed rats. Oral CCPS attenuated the above apoptotic expressional changes significantly and dietary CCPS ensured successful fertility with the birth of healthy pups in lieu of infertile condition in As3+ fed rats. Moreover, this study also supports that CCPS treatment attenuated the As3+ toxicity by modulating the S-adenosine methionine (SAM) pool components, B12, folate and homocysteine.


Assuntos
Anti-Inflamatórios/uso terapêutico , Apoptose/efeitos dos fármacos , Infertilidade Feminina/tratamento farmacológico , Momordica charantia/química , Pectinas/uso terapêutico , Animais , Anti-Inflamatórios/isolamento & purificação , Arsenitos , Catalase/metabolismo , Feminino , Expressão Gênica/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , Infertilidade Feminina/induzido quimicamente , Masculino , Ovário/patologia , Estresse Oxidativo/efeitos dos fármacos , Pectinas/isolamento & purificação , Gravidez , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Compostos de Sódio , Superóxido Dismutase/metabolismo , Útero/patologia
17.
Environ Sci Pollut Res Int ; 26(23): 23453-23459, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31201704

RESUMO

Cadmium (Cd) as a widespread toxic heavy metal accumulates in animal food including chicken meat through food chain enrichment and finally threatens human health. Selenium (Se) is an essential mineral and possesses antagonistic effects on Cd-induced multiple organs' toxicity in chickens. The objective of the present study was to reveal the antagonistic mechanisms of Se to Cd from the aspects of oxidative stress, inflammation, and meat quality in chicken breast muscles. Firstly, the results showed that Cd significantly elevated the levels of malondialdehyde (MDA), hydrogen peroxide (H2O2), and protein carbonyl, and declined the levels of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) to trigger oxidative stress in chicken breast muscles. However, Se treatment significantly alleviated Cd-induced oxidative stress by increasing the levels of GSH-Px, SOD, and CAT, and decreasing the levels of MDA, H2O2, and protein carbonyl. Secondly, Se obviously inhibited the expressions of Cd-activated inflammation-related genes including tumor necrosis factor (TNF-α), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), inducible nitric oxide synthase (iNOS), prostaglandin-endoperoxide synthase 2 (COX-2), and prostaglandin E synthase (PTGEs) in chicken breast muscles. Thirdly, meat quality-related parameters including pH45min, ultimate pH (pHu), and drip loss were also detected, and the results showed that Se markedly recovered Cd-induced dropt of pH45min and increase of drip loss in chicken breast muscles. In brief, these findings demonstrated that Se significantly alleviated Cd-induced oxidative stress and inflammation, and declined meat quality of chicken breast muscles.


Assuntos
Antioxidantes/metabolismo , Cádmio/toxicidade , Galinhas/fisiologia , Poluentes Ambientais/toxicidade , Carne/análise , Selênio/metabolismo , Animais , Cádmio/metabolismo , Catalase/metabolismo , Galinhas/metabolismo , Glutationa Peroxidase/metabolismo , Peróxido de Hidrogênio/metabolismo , Inflamação , Malondialdeído/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/metabolismo
18.
Environ Sci Pollut Res Int ; 26(23): 24010-24019, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31222653

RESUMO

Actinomycetes are a group of the Gram-positive bacteria famous for their antimicrobial, anticancer, anti-parasitic, and anti-inflammatory activities. This study aimed to investigate the efficacy of two bacterial extracts derived from two soil actinomycete strains (S19 and G30) against carbon tetrachloride (CCl4)-induced nephrotoxicity in experimental rats. Sixty-four male rats were assigned to four groups of 16 rats in each group. The 1st group was kept as a normal (control) group and given corn oil combined with the used production medium, while the 2nd group received only CCl4 (CCl4 group). On the other hand, the 3rd group (CCl4+S19) was administered CCl4 and the extract of the actinomycete strain S19 and the 4th group (CCl4+G30) received CCl4 and the extract of the actinomycete strain G30, both treatments for 8 weeks. The results revealed that the two actinomycete extracts S19 and G30 could significantly (p < 0.01) lower the elevated levels of serum creatinine, urea, and uric acid caused by the CCl4 administration. Additionally, the two actinomycete extracts improved the decreased serum total protein. Interestingly, treatment of the CCl4-intoxicated rats with S19 and G30 extracts remarkably reversed the lowered renal glutathione (GSH), glutathione peroxidase (GSH-Px), peroxidase (Px) and superoxide dismutase (SOD) activities, and the elevated lipid peroxidation (LPO) levels. The histopathological examination of the treated kidney revealed that the two actinomycete extracts improved rats against CCl4-induced kidney lesions. The present results suggested that the protective effect of the two actinomycete extracts may rely on its effect on reducing the oxidative stress and improving the antioxidant defense system.


Assuntos
Actinobacteria/metabolismo , Fatores Biológicos/metabolismo , Tetracloreto de Carbono/toxicidade , Estresse Oxidativo/fisiologia , Animais , Antioxidantes/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Rim/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Ratos , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
19.
Environ Sci Pollut Res Int ; 26(23): 23967-23980, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31222655

RESUMO

Cadmium (Cd) is a heavy metal that poses a huge potential threat to human and animal health. Therefore, it is necessary to study its damage mechanism. In the present study, we have examined the protective effects of Ganoderma lucidum triterpenoids on oxidative stress and apoptosis in the spleen of chickens induced by Cd. One hundred and twenty healthy Hailan white chickens (7-day-old) were randomly divided into the following four groups: control group, Cd group, triterpenoid group, and Cd-triterpenoid group. The chickens were euthanized on the 20th, 40th, and 60th days, and the spleens were removed. Cd and malondialdehyde (MDA) content, antioxidant enzyme (superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)) activities, and inflammatory factor (tumor necrosis factor alpha (TNF-α) and interleukin (IL-1ß and IL-6)) and apoptotic factor (caspase-3, BAX, and Bcl-2) expressions were detected. The results showed that Ganoderma lucidum triterpenoids could reduce the content of Cd and MDA; increase the antioxidant enzyme activities (SOD and GSH-Px); decrease the expression of inflammatory factors (TNF-α) and interleukin (IL-1ß and IL-6); increase the expression of apoptotic factor (Bcl-2); and decrease the expression of apoptotic factors (caspase-3 and Bax). It showed that the triterpenoids of Ganoderma lucidum had significant protective effects on oxidative stress and apoptosis of chicken spleen, which provided a theoretical basis for further prevention and treatment of cadmium poisoning.


Assuntos
Antioxidantes/metabolismo , Cádmio/toxicidade , Substâncias Perigosas/toxicidade , Reishi , Terpenos/metabolismo , Animais , Apoptose/efeitos dos fármacos , Cádmio/metabolismo , Caspase 3 , Galinhas/metabolismo , Glutationa Peroxidase/metabolismo , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/fisiologia , Baço/metabolismo , Superóxido Dismutase/metabolismo
20.
Food Chem Toxicol ; 131: 110573, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31195070

RESUMO

This study was aimed at determining if oxidative stress imbalance in testes of rats occurs after n-butylparaben (n-ButP) exposure. Young male Sprague-Dawley rats were subcutaneously treated with n-ButP during one spermatogenic cycle (57 days) at 0 (control-oil), 150, 300 and 600 mg/kg/d with peanut oil as vehicle. A non-vehicle control group was also included. Antioxidant enzyme activities (superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase) and levels of reduced and oxidized glutathione were measured in testes. Lipid peroxidation and H2O2 concentrations were also assessed. Results showed an increase of oxidative stress in oil-treated groups, excepting 600 mg/kg/d, suggesting oxidative stress due to peanut oil. A possible antioxidant effect due to n-ButP and its metabolites was suggested at 600 mg/kg/d, the only group not showing oxidative stress. An increase of calcium concentration in testes was also observed. On the other hand, a physiologically-based pharmacokinetic (PBPK) model was developed and the concentrations of n-ButP and its metabolites were simulated in plasma and testes. The peak concentration (Cmax) in testes was found slightly higher than that in plasma. The current results indicate that peanut oil can cause oxidative stress while high doses of n-ButP can act as antioxidant agent in testes.


Assuntos
Disruptores Endócrinos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Parabenos/toxicidade , Testículo/efeitos dos fármacos , Animais , Antioxidantes/farmacocinética , Antioxidantes/toxicidade , Arachis/química , Biomarcadores/metabolismo , Cálcio/metabolismo , Catalase/metabolismo , Disruptores Endócrinos/farmacocinética , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Parabenos/farmacocinética , Óleo de Amendoim/toxicidade , Ratos Sprague-Dawley
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