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1.
Georgian Med News ; (306): 137-142, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33130661

RESUMO

In humans and mammals, the homeostasis system is supported by many organs and systems, but hematopoietic remains one of the most important. A negative effect on the hematopoietic system is rejected by many factors, but the first place remains for drugs, which one in three are non-steroidal anti-inflammatory drugs (NSAIDs). The most popular among them remains the active substance "Diclofenac Sodium", which is part of many drugs. The purpose of the work is to study the action of the active substance Diclofenac sodium and its effect on the erythrocyte series of bone marrow cells of white laboratory mice in an experiment. The studies were conducted on white laboratory mice, males, 6 months old, 60 grams. The animals were divided into three groups, the first received 0.09 mg of Diclofenac sodium in the quadriceps of the thigh, the second - 0.18 mg and the third physiological solution for 96 hours. After observing all the rules of bioethics, the animals were slaughtered and the bone marrow was examined using pure immuno-magnetic separation techniques. During the study, it became known that in the first group the number of erythroblasts increased by 75%, while in the second group by 166.5%, due to the blocking of differentiation into more mature cells. The number of reticular cells decreased by 33.4%, while in the second group by 60%. A decrease in the erythrokaryocyte maturation index in the first group by 42.6% whereas in the second by 32.5%, primarily due to immature red blood cell precursors. In the first group, the leuko-erythrokaryoid ratio decreased by 9.5%, while in the second group by 12.3%. The number of megakaryocytes due to the predominant blockade of cyclooxygenase-2 increased in the first group by 266.6%, while in the second by 733.3%. It was found that the most favorable effect on red bone marrow cells has a dose of 0.09 mg, while 0.18 mg has a toxic effect and contributes to the development of cardiovascular complications.


Assuntos
Anti-Inflamatórios não Esteroides , Diclofenaco , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Células da Medula Óssea , Humanos , Lactente , Masculino , Camundongos
2.
Biomolecules ; 10(11)2020 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-33147723

RESUMO

Plants have been used as drugs to treat human disease for centuries. Ursonic acid (UNA) is a naturally occurring pentacyclic triterpenoid extracted from certain medicinal herbs such as Ziziphus jujuba. Since the pharmacological effects and associated mechanisms of UNA are not well-known, in this work, we attempt to introduce the therapeutic potential of UNA with a comparison to ursolic acid (ULA), a well-known secondary metabolite, for beneficial effects. UNA has a keto group at the C-3 position, which may provide a critical difference for the varied biological activities between UNA and ULA. Several studies previously showed that UNA exerts pharmaceutical effects similar to, or stronger than, ULA, with UNA significantly decreasing the survival and proliferation of various types of cancer cells. UNA has potential to exert inhibitory effects in parasitic protozoa that cause several tropical diseases. UNA also exerts other potential effects, including antihyperglycemic, anti-inflammatory, antiviral, and antioxidant activities. Of note, a recent study highlighted the suppressive potential of UNA against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Molecular modifications of UNA may enhance bioavailability, which is crucial for in vivo and clinical studies. In conclusion, UNA has promising potential to be developed in anticancer and antiprotozoan pharmaceuticals. In-depth investigations may increase the possibility of UNA being developed as a novel reagent for chemotherapy.


Assuntos
Antivirais/farmacologia , Triterpenos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Antiprotozoários/química , Antiprotozoários/farmacologia , Antivirais/química , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/fisiologia , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Plantas/química , Triterpenos/química , Triterpenos/metabolismo
3.
Cardiol Rev ; 28(6): 303-307, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33017365

RESUMO

Severe acute respiratory distress syndrome coronavirus 2 (COVID-19) is the cause of the current pandemic, which remains a tremendous cause of morbidity and mortality worldwide. Although there are numerous trials underway, there is currently no medication known to cure the infection. Nonsteroidal anti-inflammatory drugs (NSAIDs) are inexpensive, widely available medications with antiviral and anti-inflammatory properties and may have utility as an adjunct therapy to improve outcomes in patients with severe COVID-19 infection. A thorough PubMed literature review on the therapeutic use of NSAID was conducted to provide a comprehensive perspective of the role of NSAIDs in treating COVID-19. NSAIDs may be a useful adjunct therapy for patients with severe COVID-19 infection, but further investigation and clinical trials are necessary to ensure their safety and efficacy.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Humanos , Pandemias , Resultado do Tratamento
4.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(8): 673-679, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32958122

RESUMO

Objective To investigate the therapeutic effect and mechanism of paeoniflorin on dextran sulphate sodium (DSS)-induced ulcerative colitis (UC) mice. Methods C57BL/6 male mice were randomly divided into control group, model group, 600 mg/(kg.d) mesalazine treatment group, (12.5, 25, 50) mg/(kg.d) paeoniflorin treatment group, with 10 mice in each. All mice were treated with 30 g/L DSS for 5 days except the control group. Meanwhile, the mice in the other groups were orally administrated corresponding drugs for 10 days, while the mice in the control and model groups were given equivalent volumes of distilled water. Body mass, fecal characteristics and hematochezia of the mice were observed and recorded daily, and then disease activity index (DAI) was evaluated and calculated. Pathological changes in the colon were observed by HE staining. The levels of anti-flagellin antibody, interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in the serum were measured by ELISA. The expression levels of Toll-like receptor 5 (TLR5), myeloid differentiation factor 88 (MyD88) and nuclear factor kappa-Bp65 (NF-κBp65) in the colon tissues were evaluated by Western blot analysis and the activation of lymphocytes in mesenteric lymph node (MLN) was detected by flow cytometry. Results Compared with the control group, DAI scores in the model group were significantly raised, the colon length was significantly shortened, and the epithelium and intestinal gland disappeared. In addition, the serum levels of anti-flagellin antibody, IL-6, TNF-α and the protein levels of TLR5, MyD88, NF-κBp65 in the colon significantly increased, and the activation of T lymphocytes in MLN went up in the model group. All symptoms above were alleviated in the mesalazine and paeoniflorin groups compared with the model group. Conclusion Paeoniflorin can attenuate UC in mice by inhibiting the expression of flagellin and TLR5, and the activation of T cells.


Assuntos
Colite Ulcerativa , Glucosídeos , Ativação Linfocitária , Monoterpenos , Linfócitos T , Receptor 5 Toll-Like , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colo/efeitos dos fármacos , Sulfato de Dextrana/toxicidade , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Ativação Linfocitária/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Monoterpenos/farmacologia , Monoterpenos/uso terapêutico , Distribuição Aleatória , Linfócitos T/efeitos dos fármacos , Receptor 5 Toll-Like/genética
5.
BMJ Open ; 10(9): e040644, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32928868

RESUMO

OBJECTIVE: To review evidence on routinely prescribed drugs in the UK that could upregulate or downregulate ACE2 and potentially affect COVID-19 disease. DESIGN: Systematic review. DATA SOURCE: MEDLINE, EMBASE, CINAHL, the Cochrane Library and Web of Science. STUDY SELECTION: Any design with animal or human models examining a currently prescribed UK drug compared with a control, placebo or sham group, and reporting an effect on ACE2 level, activity or gene expression. DATA EXTRACTION AND SYNTHESIS: MEDLINE, EMBASE, CINAHL, the Cochrane Library, Web of Science and OpenGrey from inception to 1 April 2020. Methodological quality was assessed using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk-of-bias tool for animal studies and Cochrane risk-of-bias tool for human studies. RESULTS: We screened 3360 titles and included 112 studies with 21 different drug classes identified as influencing ACE2 activity. Ten studies were in humans and one hundred and two were in animal models None examined ACE2 in human lungs. The most frequently examined drugs were angiotensin receptor blockers (ARBs) (n=55) and ACE inhibitors (ACE-I) (n=22). More studies reported upregulation than downregulation with ACE-I (n=22), ARBs (n=55), insulin (n=8), thiazolidinedione (n=7) aldosterone agonists (n=3), statins (n=5), oestrogens (n=5) calcium channel blockers (n=3) glucagon-like peptide 1 (GLP-1) agonists (n=2) and Non-steroidal anti-inflammatory drugs (NSAIDs) (n=2). CONCLUSIONS: There is an abundance of the academic literature and media reports on the potential of drugs that could attenuate or exacerbate COVID-19 disease. This is leading to trials of repurposed drugs and uncertainty among patients and clinicians concerning continuation or cessation of prescribed medications. Our review indicates that the impact of currently prescribed drugs on ACE2 has been poorly studied in vivo, particularly in human lungs where the SARS-CoV-2 virus appears to enact its pathogenic effects. We found no convincing evidence to justify starting or stopping currently prescribed drugs to influence outcomes of COVID-19 disease.


Assuntos
Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Infecções por Coronavirus , Estrogênios/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hipoglicemiantes/farmacologia , Pandemias , Peptidil Dipeptidase A/efeitos dos fármacos , Pneumonia Viral , Anti-Inflamatórios não Esteroides/farmacologia , Betacoronavirus/metabolismo , Regulação para Baixo , Peptídeo 1 Semelhante ao Glucagon/agonistas , Humanos , Insulina/farmacologia , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Peptidil Dipeptidase A/metabolismo , Tiazolidinedionas/farmacologia , Reino Unido , Regulação para Cima
6.
Adv Exp Med Biol ; 1274: 29-54, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32894506

RESUMO

Prostanoids (prostaglandins, prostacyclin and thromboxane) belong to the oxylipin family of biologically active lipids generated from arachidonic acid (AA). Protanoids control numerous physiological and pathological processes. Cyclooxygenase (COX) is a rate-limiting enzyme involved in the conversion of AA into prostanoids. There are two COX isozymes: the constitutive COX-1 and the inducible COX-2. COX-1 and COX-2 have similar structures, catalytic activities, and subcellular localizations but differ in patterns of expression and biological functions. Non-selective COX-1/2 or traditional, non-steroidal anti-inflammatory drugs (tNSAIDs) target both COX isoforms and are widely used to relieve pain, fever and inflammation. However, the use of NSAIDs is associated with various side effects, particularly in the gastrointestinal tract. NSAIDs selective for COX-2 inhibition (coxibs) were purposefully designed to spare gastrointestinal toxicity, but predisposed patients to increased cardiovascular risks. These health complications from NSAIDs prompted interest in the downstream effectors of the COX enzymes as novel drug targets. This chapter describes various safety issues with tNSAIDs and coxibs, and discusses the current development of novel classes of drugs targeting the prostanoid pathway, including nitrogen oxide- and hydrogen sulfide-releasing NSAIDs, inhibitors of prostanoid synthases, dual inhibitors, and prostanoid receptor agonists and antagonists.


Assuntos
Antagonistas de Prostaglandina/farmacologia , Antagonistas de Prostaglandina/uso terapêutico , Prostaglandinas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Humanos , Prostaglandina-Endoperóxido Sintases/metabolismo
7.
Eur J Pharmacol ; 887: 173561, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32946870

RESUMO

COVID-19 pandemic presents an unprecedented challenge to identify effective drugs for treatment. Despite multiple clinical trials using different agents, there is still a lack of specific treatment for COVID-19. Having the potential role in suppressing inflammation, immune modulation, antiviral and improving respiratory symptoms, this review discusses the potential role of methylxanthine drugs like pentoxifylline and caffeine in the management of COVID-19 patients. COVID-19 pathogenesis for clinical features like severe pneumonia, acute lung injury (ALI) / acute respiratory distress syndrome (ARDS), and multi-organ failures are excessive inflammation, oxidation, and cytokine storm by the exaggerated immune response. Drugs like pentoxifylline have already shown improvement of the symptoms of ARDS and caffeine has been in clinical use for decades to treat apnea of prematurity (AOP) in preterm infants and improve respiratory function. Pentoxifylline is well-known anti-inflammatory and anti-oxidative molecules that have already shown to suppress Tumor Necrosis Factor (TNF-α) as well as other inflammatory cytokines in pulmonary diseases, and this may be beneficial for better clinical outcomes in COVID-19 patients. Pentoxifylline enhances blood flow, improves microcirculation and tissue oxygenation, and caffeine also efficiently improves tissue oxygenation, asthma, decreases pulmonary hypertension and an effective analgesic. There are significant shreds of evidence that proved the properties of pentoxifylline and caffeine against virus-related diseases as well. Along with the aforementioned evidences and high safety profiles, both pentoxifylline and caffeine offer a glimpse of considerations for future use as a potential adjuvant to COVID-19 treatment. However, additional clinical studies are required to confirm this speculation.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Pandemias , Pentoxifilina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Xantinas/farmacologia , Xantinas/uso terapêutico , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Cafeína/farmacologia , Cafeína/uso terapêutico , Infecções por Coronavirus/complicações , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Inflamação/tratamento farmacológico , Inflamação/etiologia , Pentoxifilina/farmacologia , Pneumonia Viral/complicações
8.
Medicine (Baltimore) ; 99(31): e21446, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756162

RESUMO

Aspirin (ASA) exerts an anti-tumor effect via the COX pathway. Clinical studies on the chemopreventive effects of ASA on uterine cancer (UC) remain inconsistent. We used population-based retrospective cohort study to evaluate the UC in ASA users in Taiwanese women. From insurance claims data, we identified 23,342 women received ASA treatment between 2000 and 2010 and a comparison group of same sample size randomly selected from the same database matched by the propensity score. The incidence of UC in the ASA cohort was 10% of that in the comparison group (0.28 vs 2.73 per 10,000 person-years). The Poisson regression analysis estimated adjusted incidence rate ratio (IRR) was 0.10 (95% confidence interval (CI) = 0.09-0.11) for ASA users relatives to comparisons after controlling for covariates. The UC incidence in ASA users decreased with age, from 0.61 per 10,000 person-years in the 20 to 39 years old (adjusted IRR = 0.21, 95% CI = 0.15-0.29) to 0.21 per 10,000 person-years in the 65 to 80 years old (adjusted IRR = 0.15, 95% CI = 0.12-0.16). The incidence was higher in longer term users. Hormone therapy of estradiol was associated with the increase of UC risk in both cohorts, but less in ASA users than comparisons (1.34 vs 4.75 per 10,000 person-years). This study suggests that ASA use was associated with a decreased risk of UC. Further prospective randomized clinical trials are warranted to confirm the association.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Aspirina/farmacologia , Inibidores de Ciclo-Oxigenase/farmacologia , Neoplasias Uterinas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/administração & dosagem , Aspirina/administração & dosagem , Estudos de Casos e Controles , Quimioprevenção , Estudos de Coortes , Inibidores de Ciclo-Oxigenase/administração & dosagem , Estradiol/efeitos adversos , Estrogênios/efeitos adversos , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Taiwan/epidemiologia
9.
Ecotoxicol Environ Saf ; 202: 110906, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32800241

RESUMO

The nonsteroidal anti-inflammatory drug diclofenac (DCF) is considered a contaminant of emerging concern. DCF can co-exist with heavy metals in aquatic environments, causing unexpected risks to aquatic organisms. This study aimed to assess the combined effects of DCF and cadmium (Cd) at environmentally relevant concentrations on the bioconcentration and status of oxidative stress and detoxification in Chironomus riparius larvae. The larvae were exposed to DCF (2 and 20 µg L-1) and Cd (5 and 50 µg L-1) alone or in mixtures for 48 h. The combined exposure to DCF and Cd was found to reciprocally facilitate the accumulation of each compound in larvae compared with single exposures. As indicated by the antioxidant enzyme activities, reduced glutathione levels, and malondialdehyde contents, the low concentration of the mixture (2 µg L-1 DCF + 5 µg L-1 Cd) did not alter the oxidative stress status in larvae, while the high concentration of the mixture (20 µg L-1 DCF + 50 µg L-1 Cd) induced stronger oxidative damage to larvae compared with single exposures. The expression levels of eight genes (CuZnSOD, MnSOD, CAT, GSTd3, GSTe1, GSTs4, CYP4G, and CYP9AT2) significantly decreased due to the high concentration of the mixture compared with single exposures in most cases. Overall, the results suggest that the mixture of DCF and Cd might exert greater ecological risks to aquatic insects compared with their individual compounds.


Assuntos
Cádmio/toxicidade , Chironomidae/fisiologia , Diclofenaco/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Cádmio/metabolismo , Chironomidae/efeitos dos fármacos , Diclofenaco/metabolismo , Inativação Metabólica/efeitos dos fármacos , Larva/efeitos dos fármacos , Malondialdeído/metabolismo , Metais Pesados/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Poluentes Químicos da Água/metabolismo
10.
Int J Nanomedicine ; 15: 5181-5202, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801685

RESUMO

Background: Combating infectious diseases caused by influenza virus is a major challenge due to its resistance to available drugs and vaccines, side effects, and cost of treatment. Nanomedicines are being developed to allow targeted delivery of drugs to attack specific cells or viruses. Materials and Methods: In this study, mesoporous silica nanoparticles (MSNs) functionalized with amino groups and loaded with natural prodrugs of shikimic acid (SH), quercetin (QR) or both were explored as a novel antiviral nanoformulations targeting the highly pathogenic avian influenza H5N1 virus. Also, the immunomodulatory effects were investigated in vitro tests and anti-inflammatory activity was determined in vivo using the acute carrageenan-induced paw edema rat model. Results: Prodrugs alone or the MSNs displayed weaker antiviral effects as evidenced by virus titers and plaque formation compared to nanoformulations. The MSNs-NH2-SH and MSNs-NH2-SH-QR2 nanoformulations displayed a strong virucidal by inactivating the H5N1 virus. They induced also strong immunomodulatory effects: they inhibited cytokines (TNF-α, IL-1ß) and nitric oxide production by approximately 50% for MSNs-NH2-SH-QR2 (containing both SH and QR). Remarkable anti-inflammatory effects were observed during in vivo tests in an acute carrageenan-induced rat model. Conclusion: Our preliminary findings show the potential of nanotechnology for the application of natural prodrug substances to produce a novel safe, effective, and affordable antiviral drug.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antivirais/farmacologia , Virus da Influenza A Subtipo H5N1/efeitos dos fármacos , Nanopartículas/química , Pró-Fármacos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/imunologia , Antivirais/imunologia , Citocinas/metabolismo , Cães , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Edema/tratamento farmacológico , Edema/metabolismo , Fatores Imunológicos/imunologia , Fatores Imunológicos/farmacologia , Células Madin Darby de Rim Canino , Masculino , Camundongos , Quercetina/imunologia , Quercetina/farmacologia , Ratos , Ácido Chiquímico/imunologia , Ácido Chiquímico/farmacologia , Dióxido de Silício/química
11.
Life Sci ; 258: 118213, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32768583

RESUMO

AIMS: Intermittent cyclic tension stimulation(ICMT) was shown to promote degeneration of endplate chondrocytes and induce autophagy. However, enhancing autophagy can alleviate degeneration partly. Studies have shown that curcumin can induce autophagy and protect chondrocytes, we speculated that regulation of autophagy by curcumin might be an effective method to improve the stress resistance of endplate cartilage. In this study, human cervical endplate cartilage specimens were collected, and expression of autophagy markers was detected and compared. MAIN METHODS: Human cervical endplate chondrocytes were cultured to establish a tension-induced degeneration model, for which changes of functional metabolism and autophagy levels were detected under different tension loading conditions. Changes in functional metabolism of endplate chondrocytes were observed under high-intensity tension loading in the presence of inhibitors, inducers, and curcumin to regulate the autophagy level of cells. In addition, a rat model of lumbar instability was established to observe the degeneration of lumbar disc after curcumin administration. KEY FINDINGS: Through a series of experiments, we found that low-intensity tension stimulation can maintain a stable phenotype of endplate chondrocytes, but high-intensity tension stimulation has a negative effect. Moreover, with increasing tension intensity, the degree of degeneration of endplate chondrocytes was gradually aggravated and the level of autophagy increased. Besides, curcumin upregulated autophagy, inhibited apoptosis, and reduced phenotype loss of endplate chondrocytes induced by high-intensity tension loading, thereby relieving intervertebral disc degeneration induced by mechanical imbalance. SIGNIFICANCE: Curcumin mediated autophagy and enhanced the adaptability of endplate chondrocytes to high-intensity tension load, thereby relieving intervertebral disc degeneration.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Autofagia/efeitos dos fármacos , Cartilagem/efeitos dos fármacos , Curcumina/uso terapêutico , Degeneração do Disco Intervertebral/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Autofagia/fisiologia , Cartilagem/patologia , Curcumina/farmacologia , Feminino , Degeneração do Disco Intervertebral/patologia , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/patologia , Masculino , Ratos , Ratos Sprague-Dawley
12.
PLoS One ; 15(8): e0236689, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32785240

RESUMO

OBJECTIVE: To compare the effects of photobiomodulation therapy (PBMT) and pharmacological therapy (glucocorticoids and non-steroidal anti-inflammatory drugs) applied alone and in different combinations in mdx mice. METHODS: The animals were randomized and divided into seven experimental groups treated with placebo, PBMT, prednisone, non-steroidal anti-inflammatory drug (NSAIDs), PBMT plus prednisone and PBMT plus NSAID. Wild type animals were used as control. All treatments were performed during 14 consecutive weeks. Muscular morphology, protein expression of dystrophin and functional performance were assessed at the end of the last treatment. RESULTS: Both treatments with prednisone and PBMT applied alone or combined, were effective in preserving muscular morphology. In addition, the treatments with PBMT (p = 0.0005), PBMT plus prednisone (p = 0.0048) and PBMT plus NSAID (p = 0.0021) increased dystrophin gene expression compared to placebo-control group. However, in the functional performance the PBMT presented better results compared to glucocorticoids (p<0.0001). In contrast, the use of NSAIDs did not appear to add benefits to skeletal muscle tissue in mdx mice. CONCLUSION: We believe that the promising and optimistic results about the PBMT in skeletal muscle of mdx mice may in the future contribute to this therapy to be considered a safe alternative for patients with Duchenne Muscular Dystrophy (DMD) in a washout period (between treatment periods with glucocorticoids), allowing them to remain receiving effective and safe treatment in this period, avoiding at this way periods without administration of any treatment.


Assuntos
Distrofina/genética , Terapia com Luz de Baixa Intensidade , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/efeitos da radiação , Distrofia Muscular de Duchenne/terapia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Terapia Combinada , Modelos Animais de Doenças , Progressão da Doença , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos da radiação , Glucocorticoides/farmacologia , Humanos , Camundongos , Camundongos Endogâmicos mdx , Músculo Esquelético/metabolismo , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/metabolismo , Distrofia Muscular de Duchenne/fisiopatologia , Prednisona/farmacologia
13.
Chem Biol Interact ; 330: 109230, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32828744

RESUMO

Although physiological levels of iron are essential for numerous biological processes, excess iron causes critical tissue injury. Under iron overload conditions, non-chelated iron generates reactive oxygen species that mediate iron-induced tissue injury with subsequent induction of apoptosis, necrosis, and inflammatory responses. Because liver is a central player in iron metabolism and storage, it is vulnerable to iron-induced tissue injury. Taxifolin is naturally occurring compound that has shown potent antioxidant and potential iron chelation competency. The aim of the current study was to investigate the potential protective effects of taxifolin against iron-induced hepatocellular injury and to elucidate the underlining mechanisms using rats as a mammalian model. The results of the current work indicated that taxifolin inhibited iron-induced apoptosis and enhanced hepatocellular survival as demonstrated by decreased activity of caspase-3 and activation of the pro-survival signaling PI3K/AKT, respectively. Western blotting analysis revealed that taxifolin enhanced liver regeneration as indicated by increased PCNA protein abundance. Taxifolin mitigated the iron-induced histopathological aberration and reduced serum activity of liver enzymes (ALT and AST), highlighting enhanced liver cell integrity. Mechanistically, taxifolin modulated the redox-sensitive MAPK signaling (p38/c-Fos) and improved redox status of the liver tissues as indicated by decreased lipid peroxidation and protein oxidation along with enhanced total antioxidant capacity. Interestingly, it decreased liver iron content and down-regulated the pro-inflammatory cytokines TNF-α, IL-6, and IL-1ß. Collectively, these data highlight, for the first time, the ameliorating effects of taxifolin against iron overload-induced hepatocellular injury that is potentially mediated through anti-inflammatory, antioxidant, and potential iron chelation activities.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Sobrecarga de Ferro/complicações , Regeneração Hepática/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Quercetina/análogos & derivados , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Antioxidantes/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Ferro/metabolismo , Quelantes de Ferro/farmacologia , Quelantes de Ferro/uso terapêutico , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Quercetina/farmacologia , Quercetina/uso terapêutico , Ratos
14.
Biol Res ; 53(1): 31, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32650839

RESUMO

BACKGROUND: In modern societies, sleep deprivation is a serious health problem. This problem could be induced by a variety of reasons, including lifestyle habits or neurological disorders. Chronic sleep deprivation (CSD) could have complex biological consequences, such as changes in neural autonomic control, increased oxidative stress, and inflammatory responses. The superior cervical ganglion (SCG) is an important sympathetic component of the autonomic nervous system. CSD can lead to a wide range of neurological consequences in SCG, which mainly supply innervations to circadian system and other structures. As the active component of Curcuma longa, curcumin possesses many therapeutic properties; including neuroprotective. This study aimed to evaluate the effect of CSD on the SCG histomorphometrical changes and the protective effect of curcumin in preventing these changes. METHODS: Thirty-six male rats were randomly assigned to the control, curcumin, CSD, CSD + curcumin, grid floor control, and grid floor + curcumin groups. The CSD was induced by a modified multiple platform apparatus for 21 days and animals were sacrificed at the end of CSD or treatment, and their SCGs removed for stereological and TUNEL evaluations and also spatial arrangement of neurons in this structure. RESULTS: Concerning stereological findings, CSD significantly reduced the volume of SCG and its total number of neurons and satellite glial cells in comparison with the control animals (P < 0.05). Treatment of CSD with curcumin prevented these decreases. Furthermore, TUNEL evaluation showed significant apoptosis in the SCG cells in the CSD group, and treatment with curcumin significantly decreased this apoptosis (P < 0.01). This decrease in apoptosis was observed in all control groups that received curcumin. CSD also changed the spatial arrangement of ganglionic neurons into a random pattern, whereas treatment with curcumin preserved its regular pattern. CONCLUSIONS: CSD could potentially induce neuronal loss and structural changes including random spatial distribution in the SCG neurons. Deleterious effects of sleep deprivation could be prevented by the oral administration of curcumin. Furthermore, the consumption of curcumin in a healthy person might lead to a reduction of cell death.


Assuntos
Anti-Inflamatórios não Esteroides , Curcumina , Privação do Sono , Gânglio Cervical Superior , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Curcumina/farmacologia , Masculino , Ratos , Ratos Sprague-Dawley , Privação do Sono/tratamento farmacológico , Privação do Sono/patologia , Gânglio Cervical Superior/efeitos dos fármacos
15.
Life Sci ; 256: 118016, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32603817

RESUMO

AIMS: Ischemia/reperfusion (I/R) is one of the most important causes of acute kidney injury (AKI), a clinical syndrome with kidney dysfunction and high mortality rates. New diagnostic biomarkers need to be defined to better illuminate the pathophysiology of AKI. For the first time, we aim to investigate the protective effects of Curcumin which is known for its antioxidant and anti-inflammatory properties and 12/15 lipoxygenase inhibitor LOXblock-1 on I/R induced AKI by modulating inflammatory processes, oxidative stress, apoptosis and semaphorin-plexin pathway. MAIN METHODS: The rats were divided into five groups, with eight animals per group: Sham, I/R, I/R + DMSO (1%, i.p.), I/R + Curcumin (100 mg/kg, i.p.), I/R + LOXblock-1 (2 µg/kg, i.p.). KEY FINDINGS: The renal function biomarkers (BUN, CREA and UA) in serum were significantly increased in the I/R group. The inflammatory (TNF-α, IL-6 and MCP-1), apoptotic (CYCS and CASP3) and oxidative stress parameters (MDA, MPO, TAS and TOS) measured by ELISA were significantly increased in the I/R group. In histopathological analysis, it was observed that I/R caused serious damage to kidney tissue. SEMA3A was found to increase both serum level and mRNA expression in I/R group. It was observed that curcumin and LOXblock-1 reduce inflammatory processes, oxidative stress and apoptosis via the semaphorin-plexin pathway by both measurements and histopathological analysis. Curcumin was proved more effective than LOXblock-1 with its antioxidant feature in I/R injury. SIGNIFICANCE: The current study reveals the protective effects of Curcumin and LOXblock-1 on acute kidney injury by suppressing SEMA3A as a new biomarker.


Assuntos
Lesão Renal Aguda/prevenção & controle , Derivados de Benzeno/farmacologia , Curcumina/farmacologia , Inflamação/prevenção & controle , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacologia , Apoptose/efeitos dos fármacos , Derivados de Benzeno/administração & dosagem , Moléculas de Adesão Celular/metabolismo , Curcumina/administração & dosagem , Inibidores de Lipoxigenase/administração & dosagem , Inibidores de Lipoxigenase/farmacologia , Proteínas do Tecido Nervoso/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Traumatismo por Reperfusão/fisiopatologia , Semaforina-3A/sangue , Semaforinas/metabolismo
16.
Rev Assoc Med Bras (1992) ; 66(5): 596-599, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32638962

RESUMO

AIMS Omentin is an adipokine primarily produced by visceral adipose tissue and its reduced levels have been shown to be associate with worse metabolic outcomes. We aimed to study the effects of preoperative ibuprofen on postoperative omentin levels in rats after surgery. METHODS Forty-eight albino Wistar rats, 6 in each of 8 groups according to the surgical procedure (laparotomy, laparotomy plus ibuprofen (IBU), nephrectomy, nephrectomy plus IBU, hepatectomy, hepatectomy plus IBU, splenectomy and splenectomy plus IBU). The Omentin levels of the groups were postoperatively analyzed. RESULTS The mean omentin was significantly higher in the laparotomy plus IBU group compared to the laparotomy group (p<0.001). Mean Omentin was significantly higher in the hepatectomy plus IBU group compared to the hepatectomy group (p=0.01). Mean Omentin was significantly higher in the nephrectomy plus IBU group compared to the nephrectomy group (p=0.001). CONCLUSION We suggest that preoperative ibuprofen may enhance circulating levels of Omentin, which has beneficial effects in trauma and inflammation settings in subjects that undergo minor or major abdominal surgery.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Citocinas/sangue , Ibuprofeno/farmacologia , Lectinas/sangue , Adipocinas , Animais , Humanos , Inflamação , Ratos , Ratos Wistar , Esplenectomia
18.
Mol Immunol ; 125: 162-171, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32688118

RESUMO

BACKGROUND: Baicalin has many biological properties such as anti-oxidation and anti-allergy. The current study aimed to explore the effect of Baicalin on allergic rhinitis (AR) and its potential mechanism of action. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated by density gradient centrifugation. Expression levels of Th17 and Treg cells-related proteins in nasal mucosa and peripheral blood cells were detected by real-time quantitative PCR, flow cytometry and Western blot. The mice were randomly divided into Control, ovalbumin (OVA), l-Baicalin, H-Baicalin, DSGC, 3-MA, and H-Baicalin + Rapa groups. Changes of allergic rhinitis conditions and eosinophil infiltration of the mice were detected and scored by Diff-Quik staining, and histological changes were observed by Hematoxylin & Eosin (H&E) staining and Periodate Schiff (PAS) staining. Serological changes, expression levels of interleukin-17A (IL-17A), interleukin-10 (IL-10), eosinophilic cationic protein (ECP) and anti-OVA-specific antibodies were detected by Enzyme-linked immunosorbent assay (ELISA). RESULTS: Clinical case analysis found that AR patients had a Th17/Treg imbalance and activated autophagy, however, Baicalin restored Th17/Treg cell balance and inhibited autophagy in vitro. in vivo experiments demonstrated that Baicalin inhibited OVA-induced allergic nasal symptoms and the activation of autophagy pathway, which was the same as the regulation of 3-MA, while Rapa could weaken the effects of H-baicalin. Moreover, Baicalin reduced the infiltration of different inflammatory cells of the nasal lavage fluid, prevented the damages to epithelial cells, and improved nasal mucosal thickness and mucus secretion. In addition, Baicalin regulated the balance of mouse anti-OVA-specific antibody levels and expressions of Th17/Treg-associated cytokines. CONCLUSION: Our study revealed that Baicalin can be used to treat AR, and the effect is realized through inhibiting autophagy to regulate Th17/Treg cell differentiation.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Autofagia/efeitos dos fármacos , Flavonoides/farmacologia , Rinite Alérgica/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Animais , Autofagia/imunologia , Humanos , Camundongos , Linfócitos T Reguladores/imunologia , Células Th17/imunologia
19.
Br J Pharmacol ; 177(21): 4899-4920, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32700336

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the novel coronavirus disease 2019 (COVID-19), a highly pathogenic and sometimes fatal respiratory disease responsible for the current 2020 global pandemic. Presently, there remains no effective vaccine or efficient treatment strategies against COVID-19. Non-steroidal anti-inflammatory drugs (NSAIDs) are medicines very widely used to alleviate fever, pain, and inflammation (common symptoms of COVID-19 patients) through effectively blocking production of prostaglandins (PGs) via inhibition of cyclooxyganase enzymes. PGs can exert either proinflammatory or anti-inflammatory effects depending on the inflammatory scenario. In this review, we survey the potential roles that NSAIDs and PGs may play during SARS-CoV-2 infection and the development and progression of COVID-19. LINKED ARTICLES: This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacologia , Infecções por Coronavirus/virologia , Progressão da Doença , Humanos , Inflamação/tratamento farmacológico , Inflamação/virologia , Pandemias , Pneumonia Viral/virologia , Prostaglandinas/administração & dosagem , Prostaglandinas/farmacologia
20.
JAMA Netw Open ; 3(7): e2013880, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32609352

RESUMO

Importance: During the ongoing coronavirus disease 2019 pandemic, case reports have suggested that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may lead to adverse outcomes. Objective: To study the association of NSAID use with adverse outcomes in patients hospitalized with influenza or influenza pneumonia. Design, Setting, and Participants: This cohort study used propensity score matching among 7747 individuals aged 40 years or older who were hospitalized with influenza, confirmed by polymerase chain reaction or antigen testing, between 2010 and 2018. Data were collected using Danish nationwide registers. All analyses reported were performed on May 29, 2020. Exposures: Prescription fill of an NSAID within 60 days before admission. Main Outcomes and Measures: Risk ratio (RR) and risk difference (RD) with 95% CIs for intensive care unit admission and death within 30 days of admission. Results: A total of 7747 patients (median [interquartile range] age, 71 [59-80] years, 3980 [51.4%] men) with confirmed influenza were identified. Of these, 520 (6.7%) were exposed to NSAIDs. In the unmatched cohorts, 104 of 520 patients (20.0%) who used NSAIDs and 958 of 7227 patients (13.3%) who did not use NSAIDs were admitted to the intensive care unit. For death within 30 days of admission, we observed 37 events (7.1%) among those who used NSAIDs compared with 563 events (7.8%) among those who did not. Current NSAID use was associated with intensive care unit admission (RR, 1.51; 95% CI, 1.26 to 1.81; RD, 6.7%; 95% CI, 3.2% to 10.3%), while NSAID use was not associated with death (RR, 0.91; 95% CI, 0.66 to 1.26; RD, -0.7%; 95% CI, -3.0% to 1.6%). In the matched cohorts, risks were unchanged for patients who used NSAIDs, while 83 ICU admissions (16.0%) and 36 deaths (6.9%) were observed among matched individuals who did not use NSAIDs. Matched (ie, adjusted) analyses yielded attenuated risk estimates for intensive care unit admission (RR, 1.25; 95% CI, 0.95 to 1.63; RD, 4.0%; 95% CI, -0.6% to 8.7%) and death (RR, 1.03; 95% CI, 0.66 to 1.60; RD, 0.2%; 95% CI, -2.9% to 3.3%). Associations were more pronounced among patients who used NSAIDs for a longer period (eg, for intensive care unit admission: RR, 1.90; 95% CI, 1.19 to 3.06; RD, 13.4%; 95% CI, 4.0% to 22.8%). Conclusions and Relevance: In this cohort study of adult patients hospitalized with influenza, the use of NSAIDs was not associated with 30-day intensive care unit admission or death in adjusted analyses. There was an association between long-term use of NSAIDs and intensive care unit admission.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Infecções por Coronavirus/tratamento farmacológico , Hospitalização , Unidades de Terapia Intensiva , Pneumonia Viral/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/efeitos adversos , Betacoronavirus , Estudos de Coortes , Infecções por Coronavirus/complicações , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Dinamarca/epidemiologia , Feminino , Humanos , Influenza Humana , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pandemias , Pneumonia , Pneumonia Viral/complicações , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia
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