Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 715
Filtrar
1.
J Sci Food Agric ; 100(2): 614-622, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31597198

RESUMO

BACKGROUND: Lonicera japonica Thunb is a common herb in East Asia. The flower buds are usually regarded as the traditional medicinal part, while leaves and stems are considered less valuable and receive little attention. This study compared the chemical constituents and anti-inflammatory effects of the different tissues in L. japonica Thunb for the first time. RESULTS: Thirty compounds were identified by ultra-performance liquid chromatography-photodiode detector-quadrupole / time of flight-mass spectrometry (UPLC-PDA-Q/TOF-MS/MS) analysis. Hydroxycinnamic acids, flavonoids, and iridoids were identified as the major components. The flower buds (FLJ), leaves (LLJ), and stems (SLJ) of L. japonica Thunb showed strong similarities in chemical components. The LLJ contained higher levels of hydroxycinnamic acids and flavonoids than the FLJ and SLJ. Furthermore, FLJ, LLJ, and SLJ exhibited potent anti-inflammatory activity in croton oil-induced ear edema and carrageenan-induced paw edema assays in mice. Moreover, FLJ, LLJ, and SLJ showed a cytoprotective effect on lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophages. Lipopolysaccharide-induced increases in nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) were suppressed by treatments of FLJ, LLJ, and SLJ, respectively. The LLJ possessed a stronger anti-inflammatory effect than the FLJ. CONCLUSION: Leaves and stems of L. japonica Thunb have chemical components and anti-inflammatory properties similar to flower buds, and may become alternative or supplementary sources of flower buds. © 2019 Society of Chemical Industry.


Assuntos
Anti-Inflamatórios/química , Edema/tratamento farmacológico , Lonicera/química , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Animais , Anti-Inflamatórios/administração & dosagem , Carragenina/efeitos adversos , Cromatografia Líquida de Alta Pressão , Edema/induzido quimicamente , Edema/genética , Edema/imunologia , Flavonoides/administração & dosagem , Flavonoides/química , Flores/química , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Camundongos , Folhas de Planta/química , Caules de Planta/química , Espectrometria de Massas em Tandem , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
2.
J Ethnopharmacol ; 247: 112224, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31509779

RESUMO

ETHNO-PHARMACOLOGICAL RELEVANCE: Corchorus olitorius is reportedly used in ethno-medicine to arrest threatened miscarriage and other conditions associated with excessive uterine contractions. The plant is also used as a purgative, demulscent and an anti-inflammatory agent. AIM OF THE STUDY: Against the background of ethno-medicinal use, this current work was designed to evaluate the gastrointestinal and uterine smooth muscles relaxant and anti-inflammatory effects of Corchorus olitorius leaf extract (COLE). MATERIALS AND METHODS: Pieces of uterine and gastrointestinal tissues were suspended separately in organ baths containing ideal physiological salt solutions bubbled with air and were tested for responses to standard drugs and COLE, then repeated in the presence of antagonists. Anti-inflammatory study was carried out via the egg albumin-induced paw edema model in rats. RESULTS: The application of COLE to pieces of uterine tissue significantly decreased the amplitudes of contractions in a dose dependent manner such that the highest dose applied (666.67 µg/ml) achieved a 100% inhibitory effect. Oxytocin induced contractions were also significantly inhibited by both salbutamol and COLE. On the isolated rabbit jejunum, the effect of COLE was also inhibitory and like atropine, significantly inhibited acetylcholine induced contractions. In the in vivo study, the extract inhibited charcoal meal movement in test rats when compared with control. Anti-inflammatory effect of COLE was significant and compared favourably with that of aspirin following in vivo trials. CONCLUSIONS: COLE therefore, may be a good tocolytic, anti-diarrheal and anti-inflammatory agent and offers hope of new drug discovery for such uses.


Assuntos
Anti-Inflamatórios/farmacologia , Antidiarreicos/farmacologia , Corchorus/química , Extratos Vegetais/farmacologia , Tocolíticos/farmacologia , Aborto Espontâneo/prevenção & controle , Animais , Anti-Inflamatórios/isolamento & purificação , Antidiarreicos/isolamento & purificação , Aspirina/farmacologia , Diarreia/tratamento farmacológico , Modelos Animais de Doenças , Edema/tratamento farmacológico , Edema/imunologia , Etnofarmacologia , Feminino , Motilidade Gastrointestinal/efeitos dos fármacos , Jejuno/efeitos dos fármacos , Jejuno/fisiologia , Contração Muscular/efeitos dos fármacos , Miométrio/efeitos dos fármacos , Nigéria , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Gravidez , Coelhos , Ratos , Tocolíticos/isolamento & purificação
3.
BMC Complement Altern Med ; 19(1): 263, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31547823

RESUMO

BACKGROUND: Inflammation is a symptom associated with many diseases. This symptom is treated with steroidal and non-steroidal anti-inflammatory drugs, which can cause severe side effects when used as long-term treatments. Natural products are an alternative source of new compounds with anti-inflammatory activity. Jefea gnaphalioides (Astereaceae) (A. Gray) is a plant species used to treat inflammatory problems, in Mexico. This study determined the anti-inflammatory activity and the composition of the methanol extract of Jefea gnaphalioides (MEJG). METHODS: The extract was obtained by heating the plant in methanol at boiling point for 4 h, and then the solvent was evaporated under vacuum (MEJG). The derivatization of the extract was performed using Bis-(trimethylsilyl) trifluoroacetamide, and the composition was determined by GC-MS. Total Phenols and flavonoids were determined by Folin-Ciocalteu AlCl3 reaction respectively. The antioxidant activity of MEJG was determined by DPPH method. The acute and chronic anti-inflammatory effects were evaluated on a mouse ear edema induced with 12-O-Tetradecanoylphorbol-13-acetate (TPA). Acute oral toxicity was tested in mice at doses of MEJG of 5000, 2500 and 1250 mg/kg. The levels of NO, TNF-α, IL-1ß and IL-6 were determinate in J774A.1 macrophages stimulated by Lipopolysaccharide. The production of inflammatory interleukins was measured using commercial kits, and nitric oxide was measured by the Griess reaction. RESULTS: The anti-inflammatory activity of MEJG in acute TPA-induced ear edema was 80.7 ± 2.8%. This result was similar to the value obtained with indomethacin (IND) at the same dose (74.3 ± 2.8%). In chronic TPA-induced edema at doses of 200 mg/kg, the inhibition was 45.7%, which was similar to that obtained with IND (47.4%). MEJG have not toxic effects even at a dose of 5000 mg/kg. MEJG at 25, 50, 100 and 200 µg/mL decreased NO, TNF-α, IL-1ß and IL-6 production in macrophages stimulated with LPS. The major compounds in MEJG were α-D-Glucopyranose (6.71%), Palmitic acid (5.59%), D-(+)-Trehalose (11.91%), Quininic acid (4.29%) and Aucubin (1.17%). Total phenolic content was 57.01 mg GAE/g and total flavonoid content was 35.26 mg QE/g MEJG had antioxidant activity. CONCLUSIONS: MEJG has anti-inflammatory activity.


Assuntos
Anti-Inflamatórios/administração & dosagem , Asteraceae/química , Edema/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Edema/genética , Edema/imunologia , Humanos , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação
4.
Biol Pharm Bull ; 42(8): 1419-1422, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366877

RESUMO

The pathogenic relationship of ulcerative colitis and rheumatoid arthritis is not known. Therefore, we examined dextran sodium sulfate (DSS)-induced colitis separately and in combination with a mouse arthritis model that mimics rheumatoid arthritis and evaluated the deterioration-related factors of each condition. Arthritis was induced in a collagen-induced arthritis mouse model using DBA/1JJmsSlc mice and ulcerative colitis was induced by the administration of drinking water containing 3.0% (w/v) DSS. The arthritis/DSS-treated mice developed worse colitis scores compared to that of the other groups of mice. The arthritis/DSS-treated mice did not demonstrate changes in hind foot volumes or in the concentration of matrix metalloproteinase-3 (MMP-3) in the plasma; however, plasma levels of interleukin-6 (IL-6) and tumor necrosis factor (TNF)-α were increased. Our results showed that IL-6 and TNF-α may influence the deterioration effect of colitis in arthritic mice.


Assuntos
Artrite Experimental/imunologia , Colite Ulcerativa/imunologia , Interleucina-6/sangue , Fator de Necrose Tumoral alfa/sangue , Animais , Artrite Experimental/sangue , Artrite Experimental/patologia , Colite Ulcerativa/sangue , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Colo/patologia , Sulfato de Dextrana , Edema/sangue , Edema/imunologia , Edema/patologia , Pé/patologia , Metaloproteinase 3 da Matriz/sangue , Camundongos Endogâmicos DBA
5.
Int Immunopharmacol ; 75: 105802, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31401380

RESUMO

Dihydroberberine (DHB), a hydrogenated derivative of berberine (BBR), has been firstly identified in Phellodendri Chinese Cortex (PC) by HPLC-ESI-MS/MS. Nowadays most researches on PC focus on its main components like BBR, however, the role of its naturally-occurring derivatives remains poorly defined heretofore. The present work aimed to comparatively evaluate the in vivo anti-inflammatory properties and mechanisms of DHB and BBR in three typical inflammatory murine models. The results showed that DHB effectively mitigated acetic acid-induced vascular permeability, xylene-elicited ear edema and carrageenan-caused paw edema. Meanwhile, DHB markedly attenuated the inflammatory cell infiltration in pathological sections of ears and paws. DHB was also observed to significantly decrease the production and mRNA expression levels of IL-6, IL-1ß, TNF-α, NO (iNOS) and PGE2 (COX-2), increase the release of IL-10, and inhibit the activation of NF-κB and MAPK signaling pathways. The anti-inflammatory effect of DHB was weaker than that of BBR. The results might further contribute to unraveling the pharmacodynamic basis of PC and support its ethnomedical use in the treatment of inflammatory diseases. DHB possesses good potential to be further developed into a promising anti-inflammatory alternative, and can serve as a lead template for novel anti-inflammatory candidate.


Assuntos
Anti-Inflamatórios/farmacologia , Berberina/análogos & derivados , Edema/metabolismo , Ácido Acético , Animais , Anti-Inflamatórios/uso terapêutico , Berberina/farmacologia , Berberina/uso terapêutico , Permeabilidade Capilar/efeitos dos fármacos , Carragenina , Citocinas/genética , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/imunologia , Feminino , Pé/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , NF-kappa B/metabolismo , Phellodendron , Casca de Planta , Xilenos
6.
Immunology ; 158(1): 47-59, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31315156

RESUMO

During probing and blood feeding, haematophagous mosquitoes inoculate a mixture of salivary molecules into their vertebrate hosts' skin. In addition to the anti-haemostatic and immunomodulatory activities, mosquito saliva also triggers acute inflammatory reactions, especially in sensitized hosts. Here, we characterize the oedema and the cellular infiltrate following Aedes aegypti mosquito bites in the skin of sensitized and non-sensitized BALB/c mice by flow cytometry. Ae. aegypti bites induced an increased oedema in the ears of both non-sensitized and salivary gland extract- (SGE-)sensitized mice, peaking at 6 hr and 24 hr after exposure, respectively. The quantification of the total cell number in the ears revealed that the cellular recruitment was more robust in SGE-sensitized mice than in non-sensitized mice, and the histological evaluation confirmed these findings. The immunophenotyping performed by flow cytometry revealed that mosquito bites were able to produce complex changes in cell populations present in the ears of non-sensitized and SGE-sensitized mice. When compared with steady-state ears, the leucocyte populations significantly recruited to the skin after mosquito bites in non-sensitized and sensitized mice were eosinophils, neutrophils, monocytes, inflammatory monocytes, mast cells, B-cells and CD4+ T-cells, each one with its specific kinetics. The changes in the absolute number of cells suggested two cell recruitment profiles: (i) a saliva-dependent migration; and (ii) a migration dependent on the immune status of the host. These findings suggest that mosquito bites influence the skin microenvironment by inducing differential cell migration, which is dependent on the degree of host sensitization to salivary molecules.


Assuntos
Aedes/imunologia , Quimiotaxia de Leucócito , Edema/imunologia , Mordeduras e Picadas de Insetos/imunologia , Leucócitos/imunologia , Mastócitos/imunologia , Saliva/imunologia , Pele/imunologia , Animais , Microambiente Celular , Modelos Animais de Doenças , Feminino , Cinética , Masculino , Camundongos Endogâmicos BALB C , Infiltração de Neutrófilos
7.
J Agric Food Chem ; 67(32): 8810-8818, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31318199

RESUMO

Citrus grandis (L.) Osbeck is a popular fruit cultivated around the world, and its peels are sometimes used for the treatment of cough, abdominal pain, and indigestion in China. However, the peel is discarded after fruit consumption in most cases, and its chemical constituents and biological activities have not been validated before. The present study focused on evaluation of the chemical and pharmacological profile of coumarins from peels of C. grandis against inflammation. The extracts and phytochemicals from peels of C. grandis were prepared, and anti-inflammatory activities were carried out in vivo and in vitro, including inhibiting xylene-induced ear edema and carrageenan-induced paw edema in mice and the production of inflammatory cytokines (interleukin 1ß, prostaglandin 2, and tumor-necrosis factor α) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Results indicated that methanolic extract, ethyl acetate fraction, and four major coumarins (compounds 7, 8, 13, and 16) inhibited swelling induced by xylene and carrageenan, separately, in vivo. Furthermore, 18 coumarins inhibited inflammatory factor secretion in macrophages primed by LPS, in which compounds 4, 6, 7, 10, 17 showed the most pronounced change, which were comparable to dexamethasone. In summary, peel of C. grandis showed an anti-inflammatory effect and coumarin compounds were responsible for regulating inflammatory mediators and cytokines, which might provide a novel nutritional strategy for inflammatory diseases.


Assuntos
Anti-Inflamatórios/administração & dosagem , Citrus/química , Cumarínicos/administração & dosagem , Edema/tratamento farmacológico , Frutas/química , Extratos Vegetais/administração & dosagem , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Cumarínicos/química , Cumarínicos/isolamento & purificação , Dinoprostona/imunologia , Edema/genética , Edema/imunologia , Humanos , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Células RAW 264.7 , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Resíduos/análise
8.
Int J Mol Sci ; 20(13)2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31269729

RESUMO

The stimulation of the AMP-activated kinase (AMPK) by 5-amino-1-ß-D-ribofuranosyl-imidazole-4-carboxamide (AICAR) has been associated with antihyperalgesia and the inhibition of nociceptive signaling in the spinal cord in models of paw inflammation. The attenuated nociception comes along with a strongly reduced paw edema, indicating that peripheral antiinflammatory mechanisms contribute to antinociception. In this study, we investigated the impact of AICAR on the immune cell composition in inflamed paws, as well as the regulation of inflammatory and resolving markers in macrophages. By using fluorescence-activated cell sorting (FACS) analysis and immunofluorescence, we found a significantly increased fraction of proresolving M2 macrophages and anti-inflammatory interleukin (IL)-10 in inflamed tissue, while M1 macrophages and proinflammatory cytokines such as IL-1 were decreased by AICAR in wild type mice. In AMPKα2 knock-out mice, the M2 polarization of macrophages in the paw was missing. The results were supported by experiments in primary macrophage cultures which also showed a shift to a proresolving phenotype with decreased levels of proinflammatory mediators and increased levels of antiinflammatory mediators. However, in the cell cultures, we did not observe differences between the AMPKα2+/+ and -/- cells, thus indicating that the AICAR-induced effects are at least partially AMPK-independent. In summary, our results indicate that AICAR has potent antiinflammatory and proresolving properties in inflammation which are contributing to a reduction of inflammatory edema and antinociception.


Assuntos
Aminoimidazol Carboxamida/análogos & derivados , Anti-Inflamatórios/uso terapêutico , Inflamação/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Ribonucleotídeos/uso terapêutico , Aminoimidazol Carboxamida/uso terapêutico , Animais , Células Cultivadas , Edema/complicações , Edema/tratamento farmacológico , Edema/imunologia , Hiperalgesia/complicações , Hiperalgesia/tratamento farmacológico , Hiperalgesia/imunologia , Inflamação/complicações , Inflamação/imunologia , Macrófagos/imunologia , Masculino , Camundongos Endogâmicos C57BL
9.
J Ethnopharmacol ; 242: 112052, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31265886

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Combretum aculeatum Vent was traditionally used in Sudan, Eretria and Ethiopia as anti-inflammatory in case of skin inflammation, catarrh, wounds, scorpion stings and snake bites. Nevertheless, there is no scientific information regarding this activity. AIM OF STUDY: The present study aimed to evaluate the phytochemical constituents and the scientific basis for the traditional use of Combretum aculeatum Vent through studying its anti-inflammatory properties for the first time to illustrate the putative mechanisms behind this bioactivity. MATERIALS AND METHODS: the ethanolic extract was partitioned by petroleum ether, methylene chloride, ethyl acetate, and n-butanol saturated with water. The petroleum ether fraction was saponified and the saponifiable and unsaponifiable fractions were analyzed on GC/MS. The different fractions were subjected to phytochemical investigation to isolate pure compounds. In-vivo anti-inflammatory activity of the ethanolic extract was evaluated using carrageenan induced rat paws edema method at doses of 200, 400 and 600 mg/kg and proved based on histopathological and biochemical parameters. RESULTS: Five known compounds were isolated for the first time from the aerial parts of Combretum aculeatum Vent: quercetin, vitexin, isorhamnetin 3-O-ß-glucoside, isovitexin and rutin, in addition to two previously isolated ones: ß-sitosterol and its glucoside. The ethanolic extract evidenced in-vivo anti-inflammatory activity by oral intake of 400 mg/kg of the ethanolic extract significantly (P ≥ 0.05) decreased the paw edema (only 32±1.9% increase in paw weight after 4 h) compared to indomethacin (28.6±2.5%). Moreover, it significantly suppressed the serum malondialdehyde (MDA) and nitric oxide (NO) and increased the GSH to be 11.76±0.85, 5.13±0.62 µmol/mL and 5.66±0.28 µM/mL, respectively. It diminished the serum cytokines TNF-α, IL-6 and IL-1ß levels to be 39.1±1.2, 32.6±1.1 and 37.5±1.2 pg/mL, respectively. Results are accompanied by histopathological examination. CONCLUSION: Overall, the results herein presented significant anti-inflammatory properties traditionally ascribed to Combretum aculeatum Vent. Moreover, the biochemical mechanisms associated to this action were highlighted, introducing new prospects for the development of effective anti-inflammatory herbal medicinal products.


Assuntos
Anti-Inflamatórios , Combretum , Edema/tratamento farmacológico , Compostos Fitoquímicos , Extratos Vegetais , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/toxicidade , Carragenina , Citocinas/imunologia , Edema/induzido quimicamente , Edema/imunologia , Edema/patologia , Dose Letal Mediana , Masculino , Camundongos , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/uso terapêutico , Compostos Fitoquímicos/toxicidade , Componentes Aéreos da Planta , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Extratos Vegetais/toxicidade , Ratos , Sudão
10.
Food Funct ; 10(8): 5080-5090, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31361289

RESUMO

Acanthopanax trifoliatus (L.) Merr., an edible medicinal plant from Southeast Asia, exerts a wide range of bioactivities, such as anti-inflammatory activity. However, the anti-inflammatory mechanisms of its action and active constituents remain unclear. Herein, the effects of two triterpenoids, namely impressic acid (IA) and acankoreanogenin A (AA), from A. trifoliatus in both in vitro and in vivo chronic inflammation models were investigated. The results indicated that AA and IA reduced lipopolysaccharide (LPS)-induced production of nitroxide significantly in murine macrophage RAW246.7 cells. In addition, AA and IA down-regulated the activation of NF-κB and decreased the release of inflammatory mediators (iNOS, COX-2, TNF-α, and IL-6) and tumorigenesis-associated factors (MMP-9 and VEGF) in RAW246.7 cells. Furthermore, in a tetradecanoylphorbolacetate (TPA)-treated mouse model, AA and IA could effectively attenuate mouse ear edema and pathological damage and reduced levels of cytokines including iNOS, COX-2, TNF-α, and IL-1ß. Taken together, AA and IA, being of natural origin, are promising anti-inflammatory agents and may contribute to the overall anti-inflammatory effect of A. trifoliatus.


Assuntos
Anti-Inflamatórios/administração & dosagem , Edema/tratamento farmacológico , NF-kappa B/imunologia , Triterpenos/administração & dosagem , Animais , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/imunologia , Regulação para Baixo , Edema/genética , Edema/imunologia , Feminino , Humanos , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/imunologia , Camundongos , Camundongos Endogâmicos ICR , NF-kappa B/genética , Células RAW 264.7 , Transdução de Sinais , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
11.
Inflamm Res ; 68(7): 613-632, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31079165

RESUMO

BACKGROUND: Hydrazide derivatives constitute an important class of compounds for new drug development as they are reported to possess good anti-inflammatory and analgesic activity. The present study was aimed to investigate the role of newly synthesized hydrazide derivatives N-pyrazoloyl hydrazone of isatin (PHI) and N-thiopheneacetyl hydrazone of isatin (THI) in acute and chronic inflammatory pain models induced by carrageenan and complete Freud's adjuvant (CFA). MATERIALS: PHI and THI (0.1, 1 and 10 mg/kg) pretreatments were provided intraperitoneally to male BALB/c mice prior to inflammatory inducers. Behavioral responses to inflammation and pain were evaluated by assessment of paw edema, mechanical allodynia, mechanical and thermal hyperalgesia. Cytokines production and NF-κB levels were evaluated by ELISA. Western blot analysis was performed for the detection of IκBα, p38, JNK and ERK. Hematoxylin and eosin (H&E) staining and radiographic analysis were performed to evaluate the effect of PHI and THI treatment on bone and soft tissues. Oxidative stress was determined by reduced glutathione, glutathione-S-transferase and catalase assays. Evans blue dye was used to monitor vascular protein leakage. RESULT: PHI and THI dose dependently (0.1, 1 and 10 mg/kg) reduced inflammation and pain in mice, however, the dose of 10 mg/kg exhibited significant activity. The anti-inflammatory and analgesic effects were attributed to suppression of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6) production levels. PHI and THI significantly blocked CFA-induced activation of NF-κB and MAPK signaling pathways. Oxidative stress and plasma nitrite levels were reduced remarkably. The PHI and THI (10 mg/kg) treatment did not exhibit any apparent toxicity on the liver, kidney, muscles strength, and motor co-ordination in mice. CONCLUSION: Both PHI and THI possess significant anti-inflammatory and analgesic activity via inhibition of inflammatory mediators.


Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Edema/tratamento farmacológico , Hidrazonas/uso terapêutico , Hiperalgesia/tratamento farmacológico , Isatina , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Citocinas/imunologia , Modelos Animais de Doenças , Edema/imunologia , Temperatura Alta/efeitos adversos , Hidrazonas/farmacologia , Hiperalgesia/imunologia , Masculino , Camundongos Endogâmicos BALB C , Proteínas Quinases Ativadas por Mitógeno/imunologia , NF-kappa B/imunologia , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Estômago/efeitos dos fármacos
12.
Int Immunopharmacol ; 72: 31-39, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30959369

RESUMO

Chromones are a group of natural substances with a diversity of biological activities. Herein we assessed the pharmacological potential of three chromones (1, 2 and 3) isolated from Dictyoloma vandellianum as anti-inflammatory agents using in vitro and in vivo approaches. During in vitro screening, the production of NO and cytokines by macrophages stimulated with LPS and IFN-γ was inhibited by all chromones at concentrations (5-20 µM) that did not induce cytotoxicity. Analysis of pharmacokinetic parameters (in vitro half-life and intrinsic clearance) using human liver microsomes revealed that 3 has a superior pharmacokinetic profile, compared to 1 and 2. Treatment with 3 (100 mg/kg, ip) did not affect the mice motor performance, while 1 and 2 induced motor deficit. Taking into account the pharmacokinetic profile and absence of motor impairment, 3 was selected for further pharmacological characterization. Corroborating the data from in vitro screening, treatment of cell cultures with 3 (5-20 µM) reduced TNF-α, IL-6 and IL-1ß production by stimulated macrophages. In the complete Freund's adjuvant-induced paw inflammation model in mice, 3 (25 and 50 mg/kg, ip) inhibited mechanical hyperalgesia, edema and cytokine production/release (IL-1ß, IL-6 and TNF-α). 3 (5-20 µM) also reduced the transcriptional activity of NF-κB in stimulated macrophages. Furthermore, treatment with RU486, a glucocorticoid receptor (GR) antagonist, partially prevented the inhibitory effect of 3 on macrophages, indicating that this chromone exerts its anti-inflammatory effects in part through the activation of GR. The results presented herein demonstrate the pharmacological potential of natural chromones, highlighting 3 as a possible candidate for the drug discovery process targeting new anti-inflammatory drugs.


Assuntos
Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Cromonas/farmacologia , Cromonas/uso terapêutico , Edema/tratamento farmacológico , Rutaceae , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Citocinas/imunologia , Edema/imunologia , Humanos , Fígado/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Microssomos Hepáticos/enzimologia , NF-kappa B/metabolismo , Óxido Nítrico/biossíntese , Raízes de Plantas
13.
Drug Dev Res ; 80(4): 513-518, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30908710

RESUMO

Chronic inflammatory pain is a major health problem worldwide with high prevalence in women. Cerebrolysin is a multimodal neuropeptide preparation that crosses the blood brain barrier and displays neuroprotective properties in aging and disease. Previously, we showed that cerebrolysin reduced mechanical allodynia in a model of persistent inflammation and pain. We aim to build upon the findings of our previous study by investigating the response to acute administration of cerebrolysin in two models of peripheral inflammation and assessing sex differences. We utilized the complete Freund's adjuvant (CFA) that produces maximal oedema and mechanical allodynia within days and carrageenan that produces similar effects within hours. Cerebrolysin reversed the mechanical allodynia in both sexes in CFA-treated rats. On the other hand, in rats treated with carrageenan, cerebrolysin was only effective in reducing mechanical allodynia in female rats. In conclusion, the present study shows that cerebrolysin effects may be sex-specific depending on different mechanisms that are at play in these two models of peripheral inflammatory pain. Further investigations are required to determine the factors contributing to sex differences.


Assuntos
Dor Aguda/tratamento farmacológico , Aminoácidos/uso terapêutico , Dor Crônica/tratamento farmacológico , Edema/tratamento farmacológico , Hiperalgesia/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Caracteres Sexuais , Dor Aguda/imunologia , Animais , Carragenina , Dor Crônica/imunologia , Modelos Animais de Doenças , Edema/imunologia , Feminino , Adjuvante de Freund , Hiperalgesia/imunologia , Inflamação , Masculino , Medição da Dor , Ratos Wistar , Fatores de Tempo
14.
Basic Clin Pharmacol Toxicol ; 125(3): 279-288, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30925204

RESUMO

Retrograde lung vascular perfusion can appear in high-risk surgeries. The present report is the first to study long-term retrograde perfusion of isolated perfused mouse lungs (IPLs) and to use the tyrosine kinase ephB4 and its ligand ephrinB2 as potential markers for acute lung injury. Mouse lungs were subjected to anterograde or retrograde perfusion with normal-pressure ventilation (NV) or high-pressure ventilation (=overventilation, OV) for 4 hours. Outcome parameters were cytokine, ephrinB2 and ephB4 levels in perfusate samples and bronchoalveolar lavage (BAL), and the wet-to-dry ratio. Anterograde perfusion was feasible for 4 hours, while lungs receiving retrograde perfusion presented considerable collapse rates. Retrograde perfusion resulted in an increased wet-to-dry ratio when combined with high-pressure ventilation; other physiological parameters were not affected. Cytokine levels in BAL and perfusate, as well as levels of soluble ephB4 in BAL were increased in OV, while soluble ephrinB2 BAL levels were increased in retrograde perfusion. BAL levels of ephrinB2 and ephB4 were also determined in vivo, including mice ventilated for 7 hours with normal-volume ventilation (NVV) or high-volume ventilation (HVV) with increased levels of ephB4 in HVV BAL compared to NVV. Retrograde perfusion in IPL is limited as a routine method to investigate effects due to collapse for yet unclear reasons. If successful, retrograde perfusion has an influence on pulmonary oedema formation. In BAL, ephrinB2 seems to be up-regulated by flow reversal, while ephB4 is a marker for acute lung injury.


Assuntos
Lesão Pulmonar Aguda/diagnóstico , Citocinas/análise , Edema/diagnóstico , Pulmão/cirurgia , Perfusão/efeitos adversos , Lesão Pulmonar Aguda/imunologia , Animais , Biomarcadores/análise , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/imunologia , Modelos Animais de Doenças , Edema/imunologia , Efrina-B2/análise , Estudos de Viabilidade , Feminino , Humanos , Técnicas In Vitro/métodos , Pulmão/imunologia , Camundongos , Perfusão/métodos , Receptor EphB4/análise , Receptor EphB4/imunologia , Respiração Artificial/efeitos adversos , Respiração Artificial/métodos , Fatores de Tempo , Regulação para Cima
15.
Ther Deliv ; 10(1): 21-36, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30730824

RESUMO

AIM: The current investigation is focused on solid self-microemulsifying drug-delivery systems (S-SMEDDS) of mefenamic acid (MFA) for improving pharmacodynamic activity. Methodology & results: Solubility assessment in various lipid excipients and optimization of pseudoternary plots were carried out for development of liquid SMEDDS. The optimized liquid SMEDD formulation was spray dried to solid dosage form and observed with enhanced amorphization or molecular dispersion of MFA in S-SMEDDS, as evident from x-ray diffractometry and differential scanning calorimetry studies. Enhanced in vitro dissolution rate of optimized formulation was observed, resulting in multifold enhancement in absorption profile of MFA, as compared with pure drug and marketed product. These studies further substantiate the dose reduction in SMEDDS by gaining equivalent therapeutic profile with marketed product. Enhanced analgesic and anti-inflammatory activity was observed with S-SMEDD formulations in acetic acid-induced writhings and carrageenan-induced paw edema models, respectively. CONCLUSION: The optimized S-SMEDD formulation holds great promise for enhancement of its physiochemical and biological attributes.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Portadores de Fármacos/química , Composição de Medicamentos/métodos , Ácido Mefenâmico/administração & dosagem , Ácido Acético/toxicidade , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/farmacocinética , Disponibilidade Biológica , Carragenina/imunologia , Química Farmacêutica , Modelos Animais de Doenças , Liberação Controlada de Fármacos , Edema/tratamento farmacológico , Edema/imunologia , Emulsões , Excipientes/química , Humanos , Masculino , Ácido Mefenâmico/farmacocinética , Camundongos , Dor/induzido quimicamente , Dor/tratamento farmacológico , Tamanho da Partícula , Ratos , Solubilidade , Tensoativos/química
16.
Part Fibre Toxicol ; 16(1): 3, 2019 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-30621720

RESUMO

BACKGROUND: The effects of carbon nanotubes on skin toxicity have not been extensively studied; however, our lab has previously shown that a carboxylated multi-walled carbon nanotube (MWCNT) exacerbates the 2, 4-dinitrofluorobenzene induced contact hypersensitivity response in mice. Here we examine the role of carboxylation in MWCNT skin toxicity. RESULTS: MWCNTs were analyzed by transmission electron microscopy, zetasizer, and x-ray photoelectron spectroscopy to fully characterize the physical properties. Two MWCNTs with different levels of surface carboxylation were chosen for further testing. The MWCNTs with a high level of carboxylation displayed increased cytotoxicity in a HaCaT keratinocyte cell line, compared to the MWCNTs with intermediate levels of carboxylation. However, neither functionalized MWCNT increased the level of in vitro reactive oxygen species suggesting an alternative mechanism of cytotoxicity. Each MWCNT was tested in the contact hypersensitivity model, and only the MWCNTs with greater than 20% surface carboxylation exacerbated the ear swelling responses. Analysis of the skin after MWCNT exposure reveals that the same MWCNTs with a high level of carboxylation increase epidermal thickness, mast cell and basophil degranulation, and lead to increases in polymorphonuclear cell recruitment when co-administered with 2, 4-dinitrofluorobenzene. CONCLUSIONS: The data presented here suggest that acute, topical application of low doses of MWCNTs can induce keratinocyte cytotoxicity and exacerbation of allergic skin conditions in a carboxylation dependent manner.


Assuntos
Dermatite de Contato/etiologia , Queratinócitos/efeitos dos fármacos , Nanotubos de Carbono/toxicidade , Pele/efeitos dos fármacos , Animais , Ácidos Carboxílicos/química , Degranulação Celular/efeitos dos fármacos , Degranulação Celular/imunologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citocinas/imunologia , Dermatite de Contato/imunologia , Dermatite de Contato/patologia , Dinitrofluorbenzeno/toxicidade , Edema/induzido quimicamente , Edema/imunologia , Edema/patologia , Humanos , Queratinócitos/imunologia , Queratinócitos/patologia , Camundongos Pelados , Camundongos Endogâmicos C57BL , Nanotubos de Carbono/química , Infiltração de Neutrófilos/efeitos dos fármacos , Oxirredução , Pele/imunologia , Pele/patologia
17.
J Ethnopharmacol ; 231: 325-336, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30445104

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Duguetia furfuracea (A. St. -Hil.) Saff. (Annonaceae) is commonly known in Brazil as "araticum-seco," and its root is used in folk medicine to treat inflammatory and painful disorders. However, no studies have been performed to evaluate these therapeutic activities. AIM OF THE STUDY: Investigate the chemical composition, anti-inflammatory and antinociceptive effects, and elucidate the possible antinociceptive mechanisms of action from the essential oil of D. furfuracea (EODf) underground stem bark. MATERIALS AND METHODS: Chemical composition was determined by gas chromatography and mass spectrometry (GC/MS). The paw edema induced by LPS, formalin-induced nociception, LPS-induced thermal hyperalgesia and rota-rod tests in vivo were used to evaluate the anti-inflammatory and antinociceptive effects in addition to the alteration on motor coordination. Histological analyses and an immunohistochemistry assay for iNOS were performed on mouse footpads of naive, control, 10 mg/kg EODf, and 10 mg/kg indomethacin (Ind) groups. The samples were removed at 1, 3, and 6 h after subplantar injection of LPS. In addition, the involvement of the adenosinergic, opioidergic, serotonergic, and cholinergic systems were investigated, in order to elucidate possible antinociceptive mechanisms. RESULTS: Twenty-four volatile constituents were detected and identified. (E)-asarone (21.9%), bicyclogermacrene (16.7%), 2,4,5-trimethoxystyrene (16.1%), α-gurjunene (15%), cyperene (7.8%), and (E)-caryophyllene (4.6%) were major compounds found in EODf. Oral treatment (p.o.) with EODf (1, 3, and 10 mg/kg) significantly inhibited the paw edema induced by LPS. At 10 mg/kg EODf promoted inhibition of tumor necrosis factor alpha (TNF-α) production, recruitment of polymorphonuclear (PMN) leukocytes and inducible nitric oxide synthase (iNOS) expression in paw tissue. EODf (10 and 30 mg/kg, p.o.) also reduced licking time in both phases of the formalin test and it had a significant effect on the LPS-induced thermal hyperalgesia model. The administration of caffeine (Caf) and naloxone (Nal) reversed the antinociceptive activity of EODf, in the first phase of the formalin test and in the LPS-induced thermal hyperalgesia model. Moreover, Nal was also able to abolish the antinociception caused by EODf, in the second phase of formalin test. In the rota-rod test, EODf-treated animals did not show any alteration of motor coordination. CONCLUSIONS: Our findings indicate that EODf underground stem bark produces anti-inflammatory and both central and peripheral antinociceptive effects. Furthermore, the antinociceptive activity of EODf underground stem bark is possibly mediated by adenosinergic and opioidergic pathways, and its properties do not induce effects on motor coordination. These results support the use of the folk medicine, D. furfuracea root, to treat inflammation and painful conditions.


Assuntos
Analgésicos , Annonaceae , Anti-Inflamatórios , Óleos Voláteis , Analgésicos/química , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , Annonaceae/química , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Edema/tratamento farmacológico , Edema/imunologia , Leucócitos/efeitos dos fármacos , Leucócitos/imunologia , Masculino , Camundongos , Antagonistas de Entorpecentes/farmacologia , Óxido Nítrico Sintase Tipo II/imunologia , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico , Dor/tratamento farmacológico , Medição da Dor , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Raízes de Plantas/química , Antagonistas de Receptores Purinérgicos P1/farmacologia , Fator de Necrose Tumoral alfa/imunologia
18.
J Ethnopharmacol ; 231: 205-216, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30445106

RESUMO

BACKGROUND: Tabernaemontana catharinensis, popularly known as snake skin, has been empirically used as an anti-inflammatory to treat cutaneous skin disorders. However, no study proves its effectiveness as a topical anti-inflammatory. STUDY DESIGN: We investigated the topical anti-inflammatory effect of T.catharinensis leaves crude extract (TcE) in irritant contact dermatitis models in mice and its preliminary toxicity profile. METHODS: The topical anti-inflammatory effect was evaluated by ear thickness measurement, inflammatory cell infiltration (MPO activity measurement and histological procedure) and cytokines levels. TcE qualitative phytochemical analysis was performed by UHPLC-ESI-HRMS and the TcE effect (therapeutic dose; 10 µg/ear) on preliminary toxicological parameters was also evaluated (on the 14°â€¯day of experiment). RESULTS: TcE (10 µg/ear) prevented the development of ear edema induced by cinnamaldehyde, capsaicin, arachidonic acid, phenol, and croton oil with maximum inhibition of 100% to cinnamaldehyde, arachidonic acid, phenol, and croton oil and 75 ±â€¯6% to capsaicin. Besides, the TcE (10 µg/ear) also prevented the increase of MPO activity by 96 ±â€¯2%, 48 ±â€¯7%, 100%, 87 ±â€¯8%, and 93 ±â€¯4%, respectively, to the same irritant agents. The positive controls also prevented both ear edema and the increased of MPO activity by 100% and 42 ±â€¯8% (HC-030031), 54 ±â€¯6% and 80 ±â€¯4% (SB-366791), 100% and 54 ±â€¯5% (indomethacin), 100% and 80 ±â€¯4% (dexamethasone in skin inflammation model induced by phenol) and 100% and 97 ±â€¯3% (dexamethasone in inflammation model induced by croton oil), respectively. TcE also prevented the inflammatory cells infiltration and the increase of MIP-2, IL-1ß and TNF-α levels irritant agents-induced. TcE topical anti-inflammatory effect may be attributed to the combined effect of indole alkaloids, terpenes, and phenolic compounds found in the extract and identified by dereplication method. The TcE' therapeutic dose proved to be safe in preliminary toxicological tests. CONCLUSION: Our results suggest that TcE could be an interesting strategy for the treatment of inflammatory diseases.


Assuntos
Anti-Inflamatórios/uso terapêutico , Edema/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Tabernaemontana , Animais , Citocinas/imunologia , Edema/induzido quimicamente , Edema/imunologia , Irritantes , Masculino , Camundongos , Fitoterapia , Folhas de Planta
19.
J Ethnopharmacol ; 231: 50-56, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30415057

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Mikania glomerata Spreng. (MG) and Mikania laevigata Sch. Bip. ex Baker (ML), popularly known as guaco, are medicinal plants similar in morphology, chemical composition and medicinal uses. Both species are often used and sold without distinction; however, it is believed that their chemical composition is different. AIM: Thus, the aim of this study is to investigate if the aqueous extract of MG and ML present similar anti-inflammatory activity to the point of being used interchangeably. MATERIAL AND METHODS: Different doses of both extracts and coumarin were given to rats in different experimental models to assess the anti-inflammatory activity between these two species. For this, the animals were submitted to paw edema, pleurisy and degranulation of peritoneal mast cell and the extracts were also characterized by Ultra High Efficiency Liquid Chromatography coupled to Mass Spectrometry (UHPLC-MS). RESULTS: The chromatographic method showed that ML presents ten times more coumarin than MG. Oral administration of MG, ML and coumarin inhibited paw edema induced by carrageenan (400 mg/kg, 55% inhibition; 400 mg/kg, 57% inhibition; 75 mg/kg, 38% inhibition; p < 0.05, respectively). MG, ML and coumarin treatment also inhibited the edema induced by compound 48/80 (400 mg/kg, 56% inhibition; 400 mg/kg, 69% inhibition; 75 mg/kg, 40% inhibition; p < 0.05, respectively). MG, ML and coumarin did not prevent mast cell degranulation and the consequent histamine release in Wistar rat peritoneal mast cells induced by compound 48/80. MG did not inhibit cell infiltration in pleurisy nor the highest dose tested, while ML decreased the leukocyte migration (200 and 400 mg/kg, 23% and 30% inhibition; p < 0.001, respectively) and, to a lesser extent, coumarin also reduced cell infiltration (10, 50 and 75 mg/kg; 15%, 16% and 17% inhibition; p < 0.001, respectively). CONCLUSION: The variation of the results of the anti-inflammatory activity found in M. glomerata and M. laevigata demonstrates that these two species should not be used interchangeably. Coumarin, as already proven, has anti-inflammatory action however, we have suggested that it probably is not the only component responsible for this therapeutic effect in the extracts.


Assuntos
Anti-Inflamatórios/uso terapêutico , Edema/tratamento farmacológico , Mikania , Extratos Vegetais/uso terapêutico , Pleurisia/tratamento farmacológico , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Carragenina , Degranulação Celular/efeitos dos fármacos , Edema/induzido quimicamente , Edema/imunologia , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/fisiologia , Mikania/química , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Pleurisia/induzido quimicamente , Pleurisia/imunologia , Ratos Wistar , p-Metoxi-N-metilfenetilamina
20.
Burns ; 45(3): 641-648, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30327229

RESUMO

BACKGROUND: Proper fluid resuscitation can relieve visceral damage and improve survival in severely burned patients. This study compared the effectiveness of resuscitation with 400mEq/L hypertonic saline (HS) and sodium lactate Ringer's solution (LR) in rats with kidney injury caused by burn trauma. METHODS: Rats (Sprague-Dawley) underwent burn injury and were randomized into sham, LR, and HS groups. Samples from the kidney were assayed for water content ratio, histopathology, and oxidative stress (superoxide dismutase (SOD) and malondialdehyde (MDA)). Serum sodium, renal function (creatinine and cystatin (Cys)-C), and inflammatory response (tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and high mobility group protein box (HMGB)-1) were also examined as serum markers. RESULTS: Hypertonic saline resuscitation reduced the renal water content ratio and improved renal histopathology caused by severe burns. This effect was accompanied by reductions in serum creatinine and Cys-C as well as TNF-α, IL-1ß, and HMGB1. Serum sodium concentration and SOD activity were increased, whereas MDA content was decreased in the kidney tissue of the HS group. CONCLUSIONS: The data indicate that 400mEq/L HS solution reduces hyponatremia and renal edema, inhibits the release of inflammatory mediators, and alleviates oxidative stress injury, thus protecting against kidney injury induced by severe burns.


Assuntos
Lesão Renal Aguda/metabolismo , Queimaduras/metabolismo , Hidratação/métodos , Rim/efeitos dos fármacos , Solução Salina Hipertônica/farmacologia , Lesão Renal Aguda/imunologia , Animais , Queimaduras/imunologia , Creatinina/metabolismo , Cistatina C/efeitos dos fármacos , Cistatina C/metabolismo , Edema/imunologia , Edema/metabolismo , Proteína HMGB1/efeitos dos fármacos , Proteína HMGB1/imunologia , Hiponatremia/metabolismo , Interleucina-1beta/efeitos dos fármacos , Interleucina-1beta/imunologia , Rim/metabolismo , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ressuscitação , Lactato de Ringer/farmacologia , Sódio/metabolismo , Superóxido Dismutase/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA