RESUMEN
Pain is one of the main symptoms of multiple sclerosis, a demyelinating disease of the central nervous system that affects millions of people worldwide. The experimental autoimmune encephalomyelitis (EAE) is considered an experimental model of multiple sclerosis, and besides motor weakness, hypernociception is one of the clinical signs of animals with EAE. In this study, we investigated the influence of some cytokines in the generation of the hypernociceptive response in a mouse model of EAE using MOG35-55. We measured some cytokines in the dorsal root ganglia (DRG), an important anatomical structure involved in pain. We found increased levels of the cytokines TNF-α, IL-1ß, and Kc in DRGs of animals with EAE. We used the antibody IL-1ra to antagonize the effects of IL-1ß, and animals presented a decrease in the hypernociceptive response. Thus, our results suggest that hypernociception in this experimental model of EAE may be a consequence of the increase in some cytokines in DRGs, especially IL-1ß.
Asunto(s)
Encefalomielitis Autoinmune Experimental/complicaciones , Encefalomielitis Autoinmune Experimental/metabolismo , Interleucina-1beta/metabolismo , Dolor/complicaciones , Dolor/metabolismo , Animales , Quimiocina CXCL1/metabolismo , Encefalomielitis Autoinmune Experimental/genética , Encefalomielitis Autoinmune Experimental/fisiopatología , Femenino , Ganglios Espinales/metabolismo , Ganglios Espinales/patología , Proteína Antagonista del Receptor de Interleucina 1/metabolismo , Ratones Endogámicos C57BL , Glicoproteína Mielina-Oligodendrócito , Canal de Sodio Activado por Voltaje NAV1.8/genética , Canal de Sodio Activado por Voltaje NAV1.8/metabolismo , Nocicepción , Dolor/genética , Dolor/fisiopatología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Médula Espinal/metabolismo , Médula Espinal/patología , Canales Catiónicos TRPV/genética , Canales Catiónicos TRPV/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
This study aimed to evaluate the effect of various extracts and fractions obtained from Echinodorus grandiflorus leaves on tumor necrosis factor-α release by lipopolysaccharide-stimulated THP-1 cells, as well as to look at the association between bioactivity and phytochemical composition. To this end, a high-performance liquid chromatography with diode-array detection method was developed and validated, enabling the quantification of seven compounds in E. grandiflorus extracts and fractions. All of these samples showed antitumor necrosis factor-α activity, however, extracts prepared from 50% EtOH, water and dichloromethane, and a flavonoid-rich fraction elicited the most potent responses. trans-Aconitic acid and isoorientin were the major compounds in some preparations. Polynomial regression analysis showed the association between the contents of swertiajaponin, swertisin, trans-aconitic, and chicoric acids with the antitumor necrosis factor-α activity of the extracts and fractions. None of the compounds tested alone abolished tumor necrosis factor-α release completely, however, some extracts and fractions reached this result, suggesting a synergistic effect between the constituents. Therefore, it is clearly shown that the species E. grandiflorus has significant in vitro antitumor necrosis factor-α activity, a promising characteristic that deserves further investigations in the search for new anti-inflammatory agents from plants.
Asunto(s)
Alismataceae/química , Antiinflamatorios no Esteroideos/farmacología , Extractos Vegetales/farmacología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Antiinflamatorios no Esteroideos/química , Línea Celular Tumoral , Cromatografía Líquida de Alta Presión , Humanos , Lipopolisacáridos/análisis , Fitoquímicos/análisis , Extractos Vegetales/química , Hojas de la Planta/químicaRESUMEN
BACKGROUND: The abdominal compartment syndrome (ACS) has been implicated in the pathogenesis of postinjury multiple organ failure. The ACS is defined as intra-abdominal hypertension causing adverse physiologic response. This study was designed to determine the effects of IAH on the production of interleukin-1b (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor (TNF-alpha), and the effects on remote organ injury. METHODS: IAH was induced in Sprague-Dawley rats which were divided into 5 groups, 10 animals each. Intra-abdominal pressure (IAP) was increased to 20 mm Hg for 60 and 90 minutes in two different groups. In a third group following IAP of 20 mm Hg the abdomen was decompressed for 30 minutes before samples were collected. The other animals were used as controls. Hemodynamic response was monitored throughout the procedure. Cytokine levels were assessed in the plasma. Remote organ injury was assessed by histopathology and myeloperoxidase activity. RESULTS: IAH caused a significant decrease in MAP. After abdominal decompression MAP returned to baseline levels. A significant decrease in arterial pH was also noted. Increase in the levels of TNF-alpha and IL-6 was noted 30 minutes after abdominal decompression. Plasma concentration of IL-1b was elevated after 60 minutes of IAH. Abdominal decompression, however, did not cause a significant increase in the levels of this cytokine. Lung neutrophil accumulation was significantly elevated only after abdominal decompression. Histopathological findings showed intense pulmonary inflammatory infiltration including atelectasis and alveolar edema. CONCLUSIONS: IAH provokes the release of pro-inflammatory cytokines which may serve as a second insult for the induction of MOF.