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1.
Biomolecules ; 11(8)2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34439887

RESUMO

The SARS-CoV-2 pandemic has completely disrupted the health systems of the entire planet. From the earliest months, it became increasingly clear that in addition to affecting the upper airways and lungs, there were other organs that could be affected. Among these, the skin became a real "sentinel signal" to be able to even suspect COVID-19. Background: this study deals with a little-explored issue for now: the study of skin immunopathology in SARS-CoV-2 positive subjects ascertained using the most reliable methods available. Methods: we used skin biopsy samples from SARS-CoV-2 positive and negative patients, studying morphology (Hematoxylin-Eosin), T lymphocyte population (CD4 and CD8), three markers such as HMGB-1, TIM-3 and HO-1 by immunohistochemistry. Results: although the presence of the CD4 and CD8 T population did not differ statistically significantly, we found greater activation and release of HMGB-1 in skin samples from SARS-CoV-2 positive patients, greater immunolabeling for TIM-3 at the level of CD4 and CD8 and a reduced expression of Heme oxygenase 1. Conclusions: these results support the possibility that there is immune deregulation in SARS-CoV-2 positive patients who develop skin manifestations of various kinds.


Assuntos
COVID-19/complicações , Proteína HMGB1/metabolismo , Heme Oxigenase (Desciclizante)/metabolismo , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Dermatopatias/metabolismo , Pele/metabolismo , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pele/patologia , Dermatopatias/etiologia , Dermatopatias/patologia , Linfócitos T/metabolismo
2.
Chem Biol Interact ; 347: 109599, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34343525

RESUMO

BACKGROUND: Geraniol, a natural monoterpene, is a component of many plant essential oils. It contains many medicinal and pharmacological properties. Doxorubicin is an anticancer drug; however, its clinical usage is limited due to its cumulative and dose-dependent cardiotoxicity. This study investigates geraniol as a protective agent against doxorubicin-induced cardiotoxicity and explores possible underlying mechanisms of action. METHODS: Male Sprague-Dawley rats were allocated into five groups. Groups 1 and 2 were administered saline and geraniol 200 mg/kg/day/orally, respectively, for 15 days. Group 3 was administered intraperitoneal doxorubicin (5 mg/kg/IP on the 5th, 10th and 15th days to achieve a cumulative dose of 15 mg/kg) to induce cardiotoxicity. The fourth and fifth groups were treated with either geraniol 100 mg/kg or 200 mg/kg orally and doxorubicin to equal the doxorubicin dose administered to Group 3. RESULTS: Treatment with geraniol significantly ameliorated cardiac damage and restored serum cardiac injury marker levels in doxorubicin treated animals. Geraniol upregulated Nrf2 and HO-1 expression, elevated total antioxidant capacity, decreased the nuclear accumulation of kappa-light-chain enhancer of activated B cells (NF-κB), decreased the phosphorylation and degradation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα), suppressed tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), and interleukin-18 (IL-18) levels, and restored the levels of Bax and caspase-3 and 9 in heart tissue. CONCLUSION: Geraniol may function as a potential activator of nuclear factor erythroid 2-related factor 2 (Nrf2), which subsequently improves Nrf2-dependent antioxidative signaling, diminishes apoptosis and subdues the inflammatory response. The downstream result is protection of the heart from doxorubicin-induced cardiotoxicity.


Assuntos
Monoterpenos Acíclicos/uso terapêutico , Cardiotônicos/uso terapêutico , Cardiotoxicidade/tratamento farmacológico , Cymbopogon/química , Doxorrubicina/toxicidade , Transdução de Sinais/efeitos dos fármacos , Animais , Cardiotoxicidade/patologia , Eletrocardiografia/efeitos dos fármacos , Fator de Transcrição de Proteínas de Ligação GA/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Heme Oxigenase (Desciclizante)/metabolismo , Masculino , Mitocôndrias/efeitos dos fármacos , Miocárdio/patologia , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley
3.
Life Sci ; 278: 119638, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34051216

RESUMO

Hepatotoxicity is the main adverse effect of methotrexate (MTX), which limits its clinical use and effectiveness. Both empagliflozin (EMPA) and neohesperidin dihydrochalcone (NHD) have promising criteria for suppressing oxidative stress, inflammation and apoptosis. In this current study, we suggested that EMPA and NHD exhibit protective effects against MTX-triggered liver injury, considering N-acetylcysteine (NAC) as a reference standard. In order to inspect our suggestion, An experimental rat model comprising 70 male adult rats (7 groups, 10 rats in each) was implemented to investigate the effects of MTX (20 mg/kg, i.p. once), alone or with EMPA (10 and 30 mg/kg/day, p.o.), NHD (40 and 80 mg/kg/day, p.o.), and NAC (150 mg/kg/day, p.o.) compared to the normal control animals (1%CMC, p.o.). Pre-treatment with EMPA and NHD showed significant attenuation in liver function abnormalities, pathological tissue deteriorations, hepatic oxidative stress parameters, and the level of expression of pro-inflammatory cytokines TNF-α and IL-6. Also, EMPA and NHD showed significant decreases in NF-κB/Keap1/HSP70/caspase-3 and increases in Nrf2/PPARγ/HO-1 expression levels. In addition, EMPA and NHD showed a marked enhancement of the anti-tumour activity of MTX against HepG2 and lung (A549) cancer cells. This research reveals that both EMPA and NHD can inhibit oxidation, inflammatory reactions, and apoptosis in the liver tissues of MTX-treated rats, mainly through Nrf2/PPARγ/HO-1 signalling initiation and suppression of NF-κB/Keap1/HSP70/caspase-3 axis, considered a unique class of drugs that attenuates or at least delays the onset of MTX-induced toxicity and serves as an innovative therapeutic target for future clinical application in humans.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Compostos Benzidrílicos/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Glucosídeos/uso terapêutico , Hesperidina/análogos & derivados , Metotrexato/efeitos adversos , Substâncias Protetoras/uso terapêutico , Animais , Caspase 3/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Proteínas de Choque Térmico HSP72/metabolismo , Heme Oxigenase (Desciclizante)/metabolismo , Hesperidina/uso terapêutico , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Transdução de Sinais/efeitos dos fármacos
4.
J Biol Chem ; 296: 100666, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33862082

RESUMO

Heme oxygenases (HOs) play a critical role in recouping iron from the labile heme pool. The acquisition and liberation of heme iron are especially important for the survival of pathogenic bacteria. All characterized HOs, including those belonging to the HugZ superfamily, preferentially cleave free b-type heme. Another common form of heme found in nature is c-type heme, which is covalently linked to proteinaceous cysteine residues. However, mechanisms for direct iron acquisition from the c-type heme pool are unknown. Here we identify a HugZ homolog from the oligopeptide permease (opp) gene cluster of Paracoccus denitrificans that lacks any observable reactivity with heme b and show that it instead rapidly degrades c-type hemopeptides. This c-type heme oxygenase catalyzes the oxidative cleavage of the model substrate microperoxidase-11 at the ß- and/or δ-meso position(s), yielding the corresponding peptide-linked biliverdin, CO, and free iron. X-ray crystallographic analysis suggests that the switch in substrate specificity from b-to c-type heme involves loss of the N-terminal α/ß domain and C-terminal loop containing the coordinating histidine residue characteristic of HugZ homologs, thereby accommodating a larger substrate that provides its own iron ligand. These structural features are also absent in certain heme utilization/storage proteins from human pathogens that exhibit low or no HO activity with free heme. This study thus expands the scope of known iron acquisition strategies to include direct oxidative cleavage of heme-containing proteolytic fragments of c-type cytochromes and helps to explain why certain oligopeptide permeases show specificity for the import of heme in addition to peptides.


Assuntos
Proteínas de Bactérias/metabolismo , Biliverdina/metabolismo , Heme Oxigenase (Desciclizante)/metabolismo , Heme/análogos & derivados , Heme/metabolismo , Ferro/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Paracoccus denitrificans/enzimologia , Catálise , Cristalografia por Raios X , Heme Oxigenase (Desciclizante)/química , Especificidade por Substrato
5.
Oxid Med Cell Longev ; 2021: 5896931, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33854694

RESUMO

The clinical use of doxorubicin (DOX) is limited by its cardiotoxicity, which is closely associated with oxidative stress. Xinmailong (XML) is a bioactive peptide extracted from American cockroaches, which has been mainly applied to treat chronic heart failure in China. Our previous study showed that XML attenuates DOX-induced oxidative stress. However, the mechanism of XML in DOX-induced cardiotoxicity remains unclear. Heme oxygenase-1 (HO-1), an enzyme that is ubiquitously expressed in all cell types, has been found to take antioxidant effects in many cardiovascular diseases, and its expression is protectively upregulated under DOX treatment. Lysosome and autophagy are closely involved in oxidative stress as well. It is still unknown whether XML could attenuate doxorubicin-induced lysosomal dysfunction and oxidative stress in H9c2 cells via HO-1. Thus, this study was aimed at investigating the involvement of HO-1-mediated lysosomal function and autophagy flux in DOX-induced oxidative stress and cardiotoxicity in H9c2 cells. Our results showed that XML treatment markedly increased cell proliferation and SOD activity, improved lysosomal function, and ameliorated autophagy flux block in DOX-treated H9c2 cells. Furthermore, XML significantly increased HO-1 expression following DOX treatment. Importantly, HO-1-specific inhibitor (Znpp) or HO-1 siRNA could significantly attenuate the protective effects of XML against DOX-induced cell injury, oxidative stress, lysosomal dysfunction, and autophagy flux block. These results suggest that XML protects against DOX-induced cardiotoxicity through HO-1-mediated recovery of lysosomal function and autophagy flux and decreases oxidative stress, providing a novel mechanism responsible for the protection of XML against DOX-induced cardiomyopathy.


Assuntos
Doxorrubicina/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Heme Oxigenase (Desciclizante)/metabolismo , Lisossomos/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Antibióticos Antineoplásicos/efeitos adversos , Antibióticos Antineoplásicos/farmacologia , Linhagem Celular , Doxorrubicina/efeitos adversos , Interações Medicamentosas , Heme Oxigenase (Desciclizante)/antagonistas & inibidores , Lisossomos/enzimologia , Miócitos Cardíacos/enzimologia , Ratos
6.
Life Sci ; 277: 119460, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33811899

RESUMO

BACKGROUND AND AIMS: The normal functioning of Kelch-like ECH-associated protein-1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) complex is necessary for the cellular protection against oxidative stress. We investigated the effect of chlorogenic acid (CGA), quercetin (Qt), coenzyme Q10 (Q10) and silymarin on the expression of Keap1/Nrf2 complex and its downstream target; heme oxygenase-1 (HO-1) as well as inflammation and apoptosis in an acute liver toxicity model induced by thioacetamide (TAA). MAIN METHODS: Wistar rats were divided into 13 groups: Control, silymarin, CGA, Qt, Q10, TAA (single dose 50 mg/kg, i.p.), TAA + silymarin (400 mg/kg, p.o.), TAA + CGA (100 & 200 mg/kg, p.o.), TAA + Qt (200 &300 mg/kg, p.o.) and TAA+ Q10 (30&50 mg/kg, p.o.) and treated for 8 days. KEY FINDINGS: The results showed improved liver functions and hepatic tissue integrity in all tested doses of TAA + silymarin, TAA + CGA, TAA + Qt and TAA + Q10 groups compared to the TAA group. Furthermore, these groups showed significantly lower ROS, malondialdehyde and nitric oxide levels but higher glutathione content and superoxide dismutase activity compared to the TAA group, p < 0.05. In these groups, Keap1 expression was significantly decreased while Nrf2 expression and HO-1 activity were increased. In addition, the number of apoptotic cells and the expression level of TNF-α in the liver tissues were significantly decreased compared to the TAA group. SIGNIFICANCE: CGA, Qt, Q10 and silymarin protect against TAA-induced acute liver toxicity via antioxidant, anti-inflammatory, anti-apoptotic activities and regulating Keap1-Nrf2/HO-1 expression.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Heme Oxigenase (Desciclizante)/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Ácido Clorogênico/metabolismo , Ácido Clorogênico/farmacologia , Heme Oxigenase (Desciclizante)/fisiologia , Heme Oxigenase-1/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/fisiologia , Fígado/metabolismo , Fígado/patologia , Masculino , Fator 2 Relacionado a NF-E2/fisiologia , Quercetina/metabolismo , Quercetina/farmacologia , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Silimarina/metabolismo , Silimarina/farmacologia , Tioacetamida/efeitos adversos , Tioacetamida/farmacologia , Tioacetamida/toxicidade , Ubiquinona/análogos & derivados , Ubiquinona/metabolismo , Ubiquinona/farmacologia
7.
Food Chem Toxicol ; 151: 112133, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33757793

RESUMO

Cisplatin (CIS)-induced testicular injury is a major obstacle in its application as antineoplastic agent. In this study, we investigated the protective effect and mechanism of roflumilast (ROF), a PDE4 inhibitor, against CIS-induced testicular toxicity in rats. Besides, the cytotoxic effect of CIS, with and without ROF, was evaluated on PC3 cell line. ROF reversed CIS-induced abnormalities in sperm characteristics, normalized serum testosterone level, and ameliorated CIS-induced alterations in testicular and epidydimal weights and restored normal testicular structure. Moreover, ROF increased intracellular cAMP level, PKA and HO-1 activities and Nrf2, NQO-1 and HO-1 gene expression, improved testicular oxidative stress parameters (TBARS, NO, GSH levels, and CAT activity) and inflammatory mediators (IL-1ß and TNF-α, and NF-κß p65gene expression) and reduced the proapoptotic proteins, caspase-3, Bax and increased Bcl-2. Lastly, in vitro analyses showed that ROF augmented the anticancer efficacy of CIS and enhanced the increase in gene expression of Nrf2, HO-1, and NQO-1 and the inhibition of gene expression of NF-κß p65 induced by CIS and enhanced its apoptotic effect in PC3 cells. Conclusively, PDE4 inhibition with induction of Nrf2/HO-1, NQO-1 is a potential therapeutic approach to protect male reproductive system from the detrimental effects with augmenting, the antineoplastic effect of CIS.


Assuntos
Aminopiridinas/farmacologia , Antineoplásicos/toxicidade , Benzamidas/farmacologia , Cisplatino/toxicidade , Neoplasias da Próstata/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Ciclopropanos/farmacologia , Heme Oxigenase (Desciclizante)/metabolismo , Masculino , NAD(P)H Desidrogenase (Quinona)/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Neoplasias da Próstata/patologia , Ratos , Ratos Wistar
8.
Biochemistry ; 60(12): 918-928, 2021 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-33729746

RESUMO

The noncanonical heme oxygenase MhuD from Mycobacterium tuberculosis binds a heme substrate that adopts a dynamic equilibrium between planar and out-of-plane ruffled conformations. MhuD degrades this substrate to an unusual mycobilin product via successive monooxygenation and dioxygenation reactions. This article establishes a causal relationship between heme substrate dynamics and MhuD-catalyzed heme degradation, resulting in a refined enzymatic mechanism. UV/vis absorption (Abs) and electrospray ionization mass spectrometry (ESI-MS) data demonstrated that a second-sphere substitution favoring the population of the ruffled heme conformation changed the rate-limiting step of the reaction, resulting in a measurable buildup of the monooxygenated meso-hydroxyheme intermediate. In addition, UV/vis Abs and ESI-MS data for a second-sphere variant that favored the planar substrate conformation showed that this change altered the enzymatic mechanism resulting in an α-biliverdin product. Single-turnover kinetic analyses for three MhuD variants revealed that the rate of heme monooxygenation depends upon the population of the ruffled substrate conformation. These kinetic analyses also revealed that the rate of meso-hydroxyheme dioxygenation by MhuD depends upon the population of the planar substrate conformation. Thus, the ruffled heme conformation supports rapid heme monooxygenation by MhuD, but further oxygenation to the mycobilin product is inhibited. In contrast, the planar substrate conformation exhibits altered heme monooxygenation regiospecificity followed by rapid oxygenation of meso-hydroxyheme. Altogether, these data yielded a refined enzymatic mechanism for MhuD where access to both substrate conformations is needed for rapid incorporation of three oxygen atoms into heme yielding mycobilin.


Assuntos
Biocatálise , Heme Oxigenase (Desciclizante)/metabolismo , Heme/metabolismo , Mycobacterium tuberculosis/enzimologia
9.
Arch Biochem Biophys ; 706: 108857, 2021 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-33781769

RESUMO

Accumulating evidence has demonstrated that cellular antioxidant systems play essential roles in retarding oxidative stress-related diseases, such as Parkinson's disease. Because nuclear factor erythroid 2-related factor 2 (Nrf2) is a chief regulator of cellular antioxidant systems, small molecules with Nrf2-activating ability may be promising neuroprotective agents. Avenanthramide-2c (Aven-2c), avenanthramide-2f (Aven-2f) and avenanthramide-2p (Aven-2p) are the most abundant avenanthramides in oats, and they have been documented to possess multiple pharmacological benefits. In this work, we synthesized these three compounds and evaluated their cytoprotective effect against oxidative stress-induced PC12 cell injuries. Aven-2c displayed the best protective potency among them. Aven-2c conferred protection on PC12 cells by scavenging free radicals and activating the Nrf2-ARE signaling pathway. Pretreatment of PC12 cells with Aven-2c efficiently enhanced Nrf2 nuclear accumulation and evoked the expression of a set of cytoprotective molecules. The mechanistic study also supports that Nrf2 activation is the molecular basis for the cellular action of Aven-2c. Collectively, this study demonstrates that Aven-2c is a potent Nrf2 agonist, shedding light on the potential usage of Aven-2c in the treatment of neuroprotective diseases.


Assuntos
Elementos de Resposta Antioxidante , Antioxidantes/farmacologia , Fator 2 Relacionado a NF-E2/genética , Fármacos Neuroprotetores/farmacologia , Transdução de Sinais/genética , ortoaminobenzoatos/farmacologia , Animais , Avena/química , Sobrevivência Celular/efeitos dos fármacos , Regulação da Expressão Gênica , Glutamato-Cisteína Ligase/genética , Glutamato-Cisteína Ligase/metabolismo , Heme Oxigenase (Desciclizante)/genética , Heme Oxigenase (Desciclizante)/metabolismo , Peróxido de Hidrogênio/antagonistas & inibidores , Peróxido de Hidrogênio/farmacologia , NAD(P)H Desidrogenase (Quinona)/genética , NAD(P)H Desidrogenase (Quinona)/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Oxidopamina/antagonistas & inibidores , Oxidopamina/farmacologia , Células PC12 , Extratos Vegetais/química , Ratos , Tiorredoxina Redutase 1/genética , Tiorredoxina Redutase 1/metabolismo , Tiorredoxinas/genética , Tiorredoxinas/metabolismo
10.
Inorg Chem ; 60(7): 4633-4645, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33754715

RESUMO

Human heme oxygenase (hHO-1) is a physiologically important enzyme responsible for free heme catabolism. The enzyme's high regiospecificity is controlled by the distal site hydrogen bond network that involves water molecules and the D140 amino acid residue. In this work, we probe the active site environment of the wild-type (WT) hHO-1 and its D140 mutants using resonance Raman (rR) spectroscopy. Cyanide ligands are more stable than dioxygen adducts and are an effective probe of active site environment of heme proteins. The inherently linear geometry of the Fe-C-N fragment can be altered by the steric, electrostatic, and H-bonding interactions imposed by the amino acid residues present in the heme distal site, resulting in a tilted or bent configuration. The WT hHO-1 and its D140A, D140N, and D140E mutants were studied in the presence of natural abundance CN- and its isotopic analogues (13CN-, C15N-, and 13C15N-). Deconvolution of spectral data revealed that the ν(Fe-CN) stretching and δ(Fe-CN) bending modes are present at 454 and 376 cm-1, respectively. The rR spectral patterns of the CN- adducts of WT revealed that the Fe-C-N fragment adopts a tilted conformation, with a larger bending contribution for the D140A, D140N, and D140E mutants. These studies suggest that the FeCN fragment in hHO-1 is tilted more strongly toward the porphyrin macrocycle compared to other histidine-ligated proteins, reflecting the propensity of the exogenous hHO-l ligands to position toward the α-meso-carbon, which is crucial for the HO reactivity and essential for regioselectivity.


Assuntos
Cianetos/química , Heme Oxigenase (Desciclizante)/química , Sítios de Ligação , Cianetos/metabolismo , Heme Oxigenase (Desciclizante)/genética , Heme Oxigenase (Desciclizante)/metabolismo , Humanos , Ligantes , Mutação , Análise Espectral Raman
11.
Pharmacology ; 106(5-6): 323-331, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33780953

RESUMO

BACKGROUND: Hepatic fibrosis is an inflammatory liver disease, and there is no effective therapy at present. Astilbin is a bioactive ingredient found in many medicinal and food plants, with antioxidative, anti-inflammatory, and antitumor properties. OBJECTIVES: This study aimed to investigate the protective effect and related molecular mechanism of astilbin against carbon tetrachloride (CCl4)-induced liver fibrosis in rats. METHODS: Liver fibrosis was induced by injection of CCl4 in male Sprague-Dawley rats, and those rats were then treated with astilbin at different concentrations. Pathological changes, collagen production, inflammatory cytokine, and oxidative stress were evaluated to evaluate the effects of astilbin on CCl4-induced hepatic fibrosis. Real-time PCR and western blot were performed to detect the mRNA and protein expression of indicated genes. RESULTS: We discovered that CCl4 caused significant fibrosis damage in rat liver, and astilbin dose-dependently improved the liver functions and fibrosis degree. Astilbin treatment significantly decreased collagen production, inflammatory response, and oxidative stress in vivo. Mechanically, administration of astilbin obviously elevated the hepatic levels of Nrf2 and its downstream components, including NAD(P)H:quinone oxidoreductase 1 (Nqo1), heme oxygenase (HO-1), glutamate-cysteine ligase catalytic subunit, and glutamate cysteine ligase modifier. CONCLUSIONS: Taken together, these findings demonstrate that astilbin could protect against CCL4 induced-liver fibrosis in rats.


Assuntos
Flavonóis/farmacologia , Cirrose Hepática/prevenção & controle , Substâncias Protetoras/farmacologia , Animais , Tetracloreto de Carbono/toxicidade , Colágeno/metabolismo , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Flavonóis/uso terapêutico , Glutamato-Cisteína Ligase/metabolismo , Heme Oxigenase (Desciclizante)/metabolismo , Inflamação/induzido quimicamente , Inflamação/prevenção & controle , Fígado/efeitos dos fármacos , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Masculino , NAD(P)H Desidrogenase (Quinona)/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/uso terapêutico , Ratos Sprague-Dawley
12.
Eur J Pharmacol ; 899: 174044, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33745959

RESUMO

The nuclear factor erythroid 2-related factor (Nrf2) signaling pathway has recently emerged as a novel therapeutic target in treating various diseases. Therefore, the present study aimed to assess the protective role of the Nrf2 activator, dimethyl fumarate (DMF) in the complete Freund's adjuvant (CFA)- induced arthritis model. DMF (25, 50, and 100 mg/kg) and dexamethasone (2 mg/kg) were orally administered for 14 days. Pain-related tests, paw volume, and arthritic scores were measured weekly. Serum TNF-α, IL-1ß, cyclic citrullinated peptide (CCP), C-reactive protein (CRP), and rheumatoid factor (RF) levels were estimated. Nitrite, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione (GSH), catalase (CAT), and myeloperoxidase (MPO) levels were also evaluated. NF-κB, Nrf2, HO-1, and COX-2 levels were estimated in the joint tissue. DMF treatment exerted anti-arthritic activity by enhancing the nociceptive threshold, improving arthritis scores, and reducing paw edema. Also, DMF suppressed changes in oxidative stress markers and inflammatory mediators and enhanced Nrf2 and HO-1 levels in CFA-injected rats. These findings indicate that the anti-arthritic activity of DMF may be mediated by the activation of the Nrf2/HO-1 pathway, which reduced oxidative damage and inflammation.


Assuntos
Antirreumáticos/farmacologia , Artrite Experimental/prevenção & controle , Fumarato de Dimetilo/farmacologia , Heme Oxigenase (Desciclizante)/metabolismo , Articulações/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Artrite Experimental/induzido quimicamente , Artrite Experimental/enzimologia , Artrite Experimental/patologia , Citocinas/metabolismo , Feminino , Adjuvante de Freund , Mediadores da Inflamação/metabolismo , Articulações/enzimologia , Articulações/patologia , Estresse Oxidativo/efeitos dos fármacos , Limiar da Dor/efeitos dos fármacos , Ratos Wistar , Transdução de Sinais
13.
Eur J Pharmacol ; 898: 173996, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33684450

RESUMO

Angiogenesis accelerates tissue regeneration in a variety of ischemic conditions including myocardial infarction (MI). Here we tested the hypothesis that angiogenesis induced by α7-nicotinic acetylcholine receptors (α7-nAChRs) mitigates histopathological, electrocardiographic, and molecular consequences of MI in rats. These profiles were evaluated in the isoprenaline (85 mg/kg/day i. p. For 2 days) MI rat model treated with or without nicotine or PHA-543613 (PHA, selective α7-nAChR agonist). Isoprenaline-insulted rats showed (i) ECG signs of MI such as significant ST-segment elevations and prolonged QT-intervals, (ii) deteriorated left ventricular histopathological scoring and elevated inflammatory cell infiltration, (iii) reduced immunohistochemical expression of cardiac CD34, a surrogate marker of capillary density, (iv) decreased cardiac expression of iNOS and α7-nAChRs, and (v) adaptive increases in cardiac HO-1 expression and plasma angiogenic markers such as vascular endothelial growth factor (VEGF) and nitric oxide (NO). These effects of isoprenaline, except cardiac iNOS and α7-nAChRs downregulation, were ameliorated in rats treated with a low dose (20 µg/kg/day s. c. For 16 days) of nicotine or PHA. We also show that concurrent α7-nAChR blockade by methyllycaconitine (MLA, 40 µg/kg/day, for 16 days) reversed the ECG, histopathological, and capillary density effects of nicotine, thereby reinforcing the advantageous cardioprotective and anti-ischemic roles of α7-nAChRs in this setting. The observed results showed promising effects on isoprenaline induced myocardial damage. In conclusion, the activation of α7-nAChRs by doses of nicotine or PHA in the microgram scale promotes neovascularization and offers a promising therapeutic strategy for MI. CATEGORY: Cardiovascular Pharmacology.


Assuntos
Indutores da Angiogênese/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Receptor Nicotínico de Acetilcolina alfa7/agonistas , Animais , Modelos Animais de Doenças , Heme Oxigenase (Desciclizante)/metabolismo , Isoproterenol , Masculino , Densidade Microvascular/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos Wistar , Infarto do Miocárdio com Supradesnível do Segmento ST/induzido quimicamente , Infarto do Miocárdio com Supradesnível do Segmento ST/metabolismo , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor Nicotínico de Acetilcolina alfa7/metabolismo
14.
Biochem Biophys Res Commun ; 551: 7-13, 2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33713981

RESUMO

Both the Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) antioxidant pathway and Nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) pathway are considered essential for the development of acute lung injury (ALI)/ARDS induced by sepsis. Our aim was to study the role of Nrf2/HO-1 pathway on activation of the NLRP3 in the protective effect of marrow mesenchymal stem cells (BMSCs) on LPS-induced ALI. We found that BMSCs ameliorated ALI as evidenced by 1) decreased histopathological injury, wet/dry ratio, and protein permeability index in lung; 2) decreased reactive oxygen species (ROS), malondialdehyde (MDA), and protein carbonyl content and restored the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in lung tissue; 3) reduced LPS-induced increase in inflammatory cell count and promotion of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 levels in bronchoalveolar lavage fluid (BALF); 4) improvement in the four-day survival rate of animals; and 5) enhanced expression of Nrf2 and HO-1 and decreased expression of NOD-like receptor protein 3(NLRP3) and caspase-1 (p20) in lung tissue. Of note, Nrf2 transcription factor inhibitor brusatol and HO-1 inhibitor tin protoporphyrin IX (SnppIX) reversed BMSCs induced down-expression of NLRP3 and caspase-1 (p20), and inhibited the protective effects of BMSCs. These findings demonstrated that the Nrf2-mediated HO-1 signaling pathway plays a critical role in the protective effects of BMSCs on LPS-induced ALI. BMSCs may play an anti-inflammatory effect partly through the Nrf2/HO-1-dependent NLRP3 pathway.


Assuntos
Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/prevenção & controle , Células da Medula Óssea/citologia , Endotoxinas/efeitos adversos , Heme Oxigenase (Desciclizante)/metabolismo , Células-Tronco Mesenquimais/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Antioxidantes/metabolismo , Permeabilidade Capilar/efeitos dos fármacos , Regulação da Expressão Gênica , Heme Oxigenase (Desciclizante)/antagonistas & inibidores , Inflamassomos/efeitos dos fármacos , Inflamassomos/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Pulmão/irrigação sanguínea , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Células-Tronco Mesenquimais/citologia , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Taxa de Sobrevida
15.
Oxid Med Cell Longev ; 2021: 8364297, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33623635

RESUMO

Advanced age is an independent risk factor for cardiovascular diseases, which might be further exacerbated by estrogen deficiency. Hormone replacement therapy (HRT) decreases cardiovascular risks and events in postmenopausal women; however, its effects are not fully elucidated in older individuals. Thus, the aim of our study is to examine the impact of HRT on oxidant/antioxidant homeostasis and cardiac remodeling. In our experiment, control (fertile) and aging (~20-month-old) female Wistar rats were used. Aging rats were further divided into estrogen- (E2, 0.1 mg/kg/day per os) or raloxifene- (RAL, 1.0 mg/kg/day per os) treated subgroups. After 2 weeks of treatment, cardiac heme oxygenase (HO) activity, total glutathione (GSH) content, matrix metalloproteinase-2 (MMP-2) activity, and the concentrations of collagen type I and tissue inhibitor of metalloproteinase (TIMP-2), as well as the infarct size, were determined. The aging process significantly decreased the antioxidant HO activity and GSH content, altered the MMP-2/TIMP-2 signaling, and resulted in an excessive collagen accumulation, which culminated in cardiovascular injury. However, 2 weeks of either E2 or RAL treatment enhanced the antioxidant defense mechanisms and attenuated cardiac remodeling related to aging. Our findings clearly show that 2-week-long HRT is a potential intervention to bias successful cardiovascular aging via reducing oxidative damage and cardiovascular dysfunction.


Assuntos
Envelhecimento/patologia , Terapia de Reposição Hormonal , Estresse Oxidativo , Remodelação Ventricular , Animais , Colágeno Tipo I/metabolismo , Estrogênios/farmacologia , Feminino , Glutationa/metabolismo , Heme Oxigenase (Desciclizante)/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Miocárdio/enzimologia , Miocárdio/patologia , Estresse Oxidativo/efeitos dos fármacos , Cloridrato de Raloxifeno/farmacologia , Ratos Wistar , Remodelação Ventricular/efeitos dos fármacos
16.
Int J Mol Sci ; 22(3)2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33573145

RESUMO

Renal ischemia and reperfusion (I/R) injury is the most common cause of acute kidney injury (AKI). Pathogenesis of postischemic AKI involves hemodynamic changes, oxidative stress, inflammation process, calcium ion overloading, apoptosis and necrosis. Up to date, therapeutic approaches to treat AKI are extremely limited. Thus, the aim of this study was to evaluate the effects of hyperbaric oxygen (HBO) preconditioning on citoprotective enzyme, heme oxygenase-1 (HO-1), pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins expression, in postischemic AKI induced in normotensive Wistar and spontaneously hypertensive rats (SHR). The animals were randomly divided into six experimental groups: SHAM-operated Wistar rats (W-SHAM), Wistar rats with induced postischemic AKI (W-AKI) and Wistar group with HBO preconditioning before AKI induction (W-AKI + HBO). On the other hand, SHR rats were also divided into same three groups: SHR-SHAM, SHR-AKI and SHR-AKI + HBO. We demonstrated that HBO preconditioning upregulated HO-1 and anti-apoptotic Bcl-2 protein expression, in both Wistar and SH rats. In addition, HBO preconditioning improved glomerular filtration rate, supporting by significant increase in creatinine, urea and phosphate clearances in both rat strains. Considering our results, we can also say that even in hypertensive conditions, we can expect protective effects of HBO preconditioning in experimental model of AKI.


Assuntos
Injúria Renal Aguda/prevenção & controle , Heme Oxigenase (Desciclizante)/metabolismo , Oxigenação Hiperbárica/métodos , Hipertensão/complicações , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/patologia , Injúria Renal Aguda/urina , Animais , Creatinina/metabolismo , Creatinina/urina , Modelos Animais de Doenças , Humanos , Hipertensão/fisiopatologia , Hipertensão/terapia , Rim/irrigação sanguínea , Rim/patologia , Rim/fisiopatologia , Masculino , Oxigênio/administração & dosagem , Fosfatos/metabolismo , Fosfatos/urina , Ratos , Ratos Endogâmicos SHR , Ratos Wistar , Eliminação Renal/fisiologia , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/urina , Regulação para Cima , Ureia/metabolismo , Ureia/urina
17.
Biochem Biophys Res Commun ; 547: 125-130, 2021 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-33610040

RESUMO

ABJECTIVE: Interaction of hypertension and hyperhomocysteinemia (HHcy) leads to enhanced cardiac remodeling in hypertensive heart disease. However, the mechanism of collagen accumulation and cardiac remodeling remains unclear. In this study, we attempted to evaluate the relationship between hypertension and HHcy in the context of cardiac remodeling and to explore its mechanism of action. METHODS: Wistar Kyoto (WKY) and spontaneous hypertension rats (SHR) were randomly divided into four groups, namely WKY group, WKY + HHcy group, SHR group and SHR + HHcy group. We measured blood pressure (BP), plasma homocysteine (Hcy), serum superoxide dismutase (SOD) and serum malondialdehyde (MDA). We also examined cardiac histopathology and gene and protein expression levels of Nrf2 and HO-1. RESULTS: Compared with the WKY group, myocardial interstitial and perivascular collagen deposition in the WKY + HHcy group, the SHR group and the SHR + HHcy group increased successively, indicating that cardiac remodeling gradually increased, and HHcy aggravated cardiac remodeling was more serious in hypertensive rats. SOD decreased gradually in the four groups, while MDA was on the contrary. WKY + HHcy and SHR + HHcy groups both suppressed Nrf2 and HO-1 expression and inhibited the translocation of Nrf2 from cytoplasm to nucleus compared with their control groups, and the SHR + HHcy group had a stronger inhibitory effect. CONCLUSION: HHcy enhanced cardiac remodeling in rats by enhancing oxidative stress, suppressing the Nrf2/HO-1 pathway and Nrf2 nuclear transport, and this inhibitory effect was stronger in the context of hypertension.


Assuntos
Cardiopatias/metabolismo , Heme Oxigenase (Desciclizante)/metabolismo , Hiper-Homocisteinemia/metabolismo , Hipertensão/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Remodelação Ventricular , Animais , Modelos Animais de Doenças , Cardiopatias/etiologia , Cardiopatias/patologia , Hiper-Homocisteinemia/patologia , Hipertensão/patologia , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Transdução de Sinais
18.
Eur J Pharmacol ; 898: 173932, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33631180

RESUMO

We aimed to investigate the role and mechanism of sevoflurane (SEV) preconditioning in liver ischemia-reperfusion (I/R) injury. In vivo, rats were randomly divided into Sham group, I/R rat model group, I/R + SEV group and SEV group. In vitro, hypoxia-reoxygenation (H/R) cell model were established. Hematoxylin-Eosin (H&E) and TUNEL assay were used to evaluate the degree of tissue damage and detect apoptosis in rats, respectively. HO-1, nuclear Nrf2 and cytosolic Nrf2 expressions were detected by immunohistochemical staining, Western blot analysis and quantitative real-time PCR (qRT-PCR), respectively. Contents of Lactate dehydrogenase (LDH), malondialdehyde (MDA), and reactive oxygen species (ROS) were determined by corresponding kits. Inflammatory factor levels, cell viability, apoptosis were detected by enzyme-linked immunosorbent assay (ELISA), MTT assay, and flow cytometry, respectively.In the I/R group, liver damage was severe, apoptosis-positive cells were increased, HO-1 and nuclear Nrf2 expressions were increased, and cytosolic Nrf2 expression was decreased. After SEV pretreatment, the degree of liver injury and apoptosis in rats were significantly reduced, HO-1 and nuclear Nrf2 expressions were increased significantly, and cytosolic Nrf2 expression was decreased. 4% SEV had the best mitigating effect on H/R-induced liver cell damage, as evidenced by reduced contents of LDH and MDA, decreased inflammatory factors, a lowered apoptosis rate, inhibited ROS production, effectively promoted Nrf2 nucleation, and activated Nrf/HO-1 pathway. ML385 pretreatment significantly inhibited the effect of SEV on hepatocytes.Sevoflurane protects the liver from ischemia-reperfusion injury by regulating the Nrf2/HO-1 pathway.


Assuntos
Heme Oxigenase (Desciclizante)/metabolismo , Heme Oxigenase-1/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatopatias/prevenção & controle , Fígado/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Sevoflurano/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Modelos Animais de Doenças , Heme Oxigenase (Desciclizante)/genética , Heme Oxigenase-1/genética , Hepatócitos/enzimologia , Hepatócitos/patologia , Mediadores da Inflamação/metabolismo , Fígado/enzimologia , Fígado/patologia , Hepatopatias/enzimologia , Hepatopatias/patologia , Masculino , Proteínas de Membrana/genética , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/enzimologia , Traumatismo por Reperfusão/patologia , Transdução de Sinais
19.
Mol Cell Biochem ; 476(3): 1541-1554, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33394271

RESUMO

Protective effect of Tagetes erecta flowers essential oils was investigated on oxidative stress, immune response, inflammation, and apoptosis against N-methyl-N'nitro-N-nitroguanidine (MNNG) induced gastric cancer in rats. Essential oil were extracted from Tagetes erecta flowers and analyzed using gas chromatography-mass spectrometry (GC-MS). For observing a protective effect against MNNG induced gastric cancer, we divided rats into 4 groups (group A to D) having 10 rats in each group. Performed various experiments and measured a different parameters to investigate antioxidant activity, immune response, anti-inflammatory and anti-apoptotic activity. The levels of malondialdehyde were markedly increased in the presence of N-methyl-N'nitro-N-nitroguanidine, whereas, the antioxidant activities of superoxide dismutase, and catalase were lowered in the treated rats in contrast with the control. Intervention with TEEO to gastric cancer-induced rats upregulated the redox status and the activity of the immune system to decrease cancer risk. The proinflammatory cytokines (IL-6 and TNF-α) secretions that were induced by MNNG were markedly inhibited by TEEO. Administration of TEEO also significantly reduced terminal deoxynucleotidyl transferase dUTP nick end labeling positive gastric cancer cells, expression of mRNA of caspase-3, and Bax. Whereas, the expression of Bcl-2 was increased. Additionally, downregulation of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) and IκBα degradation and the nuclear factor-κB (NF-κB) p65 expression in tissues of the stomach of MNNG-induced-rats were markedly elevated due to TEEO. This suggested possession of TEEO with a protective shield against MNNG induced gastric cancer by the exertion of antioxidative stress, anti-apoptotic response, the anti-inflammatory response through Nrf2/HO-1, and NF-κB signaling pathways.


Assuntos
Flores/metabolismo , Fator de Transcrição de Proteínas de Ligação GA/metabolismo , Heme Oxigenase (Desciclizante)/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas de Transporte Nucleocitoplasmático/metabolismo , Neoplasias Gástricas/metabolismo , Tagetes/metabolismo , Animais , Antioxidantes/metabolismo , Apoptose , Catalase/metabolismo , Linhagem Celular Tumoral , Cromatografia Gasosa-Espectrometria de Massas , Guanidinas , Imunoglobulina A/química , Imunoglobulina G/química , Imunoglobulina M/química , Inflamação , Masculino , Metilnitronitrosoguanidina/química , Camundongos , Óleos Voláteis/química , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais
20.
J Ethnopharmacol ; 270: 113793, 2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33421599

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Myrrh, a traditional remedy, is the stem resinous exudate of Commiphora molmol Engler (Burseraceae). The aromatic yellowish-brown oleoresin has a long history in folk and traditional medicine, in Saudi Arabia and the Arab world. Severe universal concern attributable to the high mortality is Myocardial Infarction (MI). Acute administration of Isoproterenol (ISO) is an established animal model to induce myocardial injury. OBJECTIVE: The existing animal study was outlined to inspect the actions of Myrrh essential oil on cardiac functional, antioxidant status, apoptotic and inflammatory deviations in isoproterenol induced MI. MATERIALS AND METHODS: Normal and Myrrh control animals were administered normal saline and Myrrh essential oil for thirty days orally, respectively. On the 29th and 30th day, the animals were injected by saline (s.c.). In the ISO control, the animals were administered saline orally for 30 days and then confronted with ISO (85 mg/kg s.c.) on 29th and 30th days. In the Myrrh Groups (IV and V), the animals were treated with Myrrh essential oil (50 and 100 mg/k) respectively for 30 days and injected with ISO (85 mg/kg, s.c.) on 29th and 30th days. RESULTS: Animals experienced MI displayed functional blood pressure deviations, intensification in the heart to body weight ratio, myocytes indicative markers (CK-MB, CPK, LDH, cTnT, cTnI), lipid peroxidation (MDA), protein expression of Nrf2 and HO-1, apoptotic markers (Caspase 3,9), and inflammatory indicators. Conversely, animals pre-treated with Myrrh revealed obliteration of those elevations triggered by ISO induction, diminished elevated biochemical values and improved heart function. CONCLUSION: Myrrh abstain effective cardio-protective action in MI model through improving the oxidative condition with myocytes and abolishing apoptotic as well as inflammatory responses.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Cardiotônicos/farmacologia , Infarto do Miocárdio/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Terpenos/farmacologia , Animais , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Biomarcadores/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Cardiotônicos/química , Cardiotônicos/uso terapêutico , Commiphora/química , Heme Oxigenase (Desciclizante)/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Isoproterenol/toxicidade , Peroxidação de Lipídeos/efeitos dos fármacos , Medicina Tradicional , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Fator 2 Relacionado a NF-E2/metabolismo , Óleos Voláteis/química , Ratos Wistar , Arábia Saudita , Terpenos/química , Terpenos/uso terapêutico
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