RESUMEN
PURPOSE: Choline-containing dietary phospholipids, including phosphatidylcholine (PC), may function as anti-inflammatory substances, but the mechanism remains largely unknown. We investigated the effects of L-alpha-glycerylphosphorylcholine (GPC), a deacylated PC derivative, in a rodent model of small intestinal ischaemia-reperfusion (IR) injury. METHODS: Anaesthetized Sprague-Dawley rats were divided into control, mesenteric IR (45 min mesenteric artery occlusion, followed by 180 min reperfusion), IR with GPC pretreatment (16.56 mg kg⻹ GPC i.v., 5 min prior to ischaemia) or IR with GPC post-treatment (16.56 mg kg⻹ GPC i.v., 5 min prior to reperfusion) groups. Macrohaemodynamics and microhaemodynamic parameters were measured; intestinal inflammatory markers (xanthine oxidoreductase activity, superoxide and nitrotyrosine levels) and liver ATP contents were determined. RESULTS: The IR challenge reduced the intestinal intramural red blood cell velocity, increased the mesenteric vascular resistance, the tissue xanthine oxidoreductase activity, the superoxide production, and the nitrotyrosine levels, and the ATP content of the liver was decreased. Exogenous GPC attenuated the macro- and microcirculatory dysfunction and provided significant protection against the radical production resulting from the IR stress. The GPC pretreatment alleviated the hepatic ATP depletion, the reductions in the mean arterial pressure and superior mesenteric artery flow, and similarly to the post-treatments with GPC, also decreased the xanthine oxidoreductase activity, the intestinal superoxide production, the nitrotyrosine level, and normalized the microcirculatory dysfunction. CONCLUSIONS: These data demonstrate the effectiveness of GPC therapies and provide indirect evidence that the anti-inflammatory effects of PC could be linked to a reaction involving the polar part of the molecule.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Suplementos Dietéticos , Modelos Animales de Enfermedad , Enteritis/prevención & control , Glicerilfosforilcolina/uso terapéutico , Intestino Delgado/irrigación sanguínea , Daño por Reperfusión/prevención & control , Adenosina Trifosfato/metabolismo , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Enteritis/etiología , Fármacos Gastrointestinales/uso terapéutico , Glicerilfosforilcolina/administración & dosificación , Mucosa Intestinal/irrigación sanguínea , Mucosa Intestinal/inmunología , Mucosa Intestinal/metabolismo , Intestino Delgado/inmunología , Intestino Delgado/metabolismo , Hígado/irrigación sanguínea , Hígado/inmunología , Hígado/metabolismo , Masculino , Isquemia Mesentérica/fisiopatología , Microcirculación , Estrés Oxidativo , Distribución Aleatoria , Ratas Sprague-Dawley , Especies de Nitrógeno Reactivo/antagonistas & inhibidores , Especies de Nitrógeno Reactivo/metabolismo , Daño por Reperfusión/etiología , Daño por Reperfusión/inmunología , Daño por Reperfusión/fisiopatología , Factores de TiempoRESUMEN
PURPOSE: To detect the possible biochemical signs of inflammatory activation in the peripheral circulation in a rodent model of hippocampus irradiation, and to examine the effects of L-alpha-glycerylphosphorylcholine (GPC) in this experimental protocol. MATERIALS AND METHODS: Anesthetized Sprague-Dawley rats were subjected to 40 Gy cobalt irradiation of both hemispheres of the hippocampus, with or without GPC treatment (50 mg/kg intravenously (i.v.), 5 min before the irradiation, n = 6, each). A third group (n = 6) served as saline-treated control. Blood samples were obtained 3 h after the end of irradiation in order to examine the changes in plasma histamine, tumor necrosis factor-alpha (TNF-α), interleukin 1-beta, interleukin 6 (IL-6) and interleukin 10 (IL-10); liver tissue samples were taken to determine adenosine triphosphate (ATP) concentrations. RESULTS: The hepatic ATP levels were significantly declined, while plasma concentrations of circulating TNF-α, IL-6, IL-10 and histamine were significantly increased after hippocampus irradiation. GPC treatment significantly reduced the irradiation-induced release of cytokines and histamine, and the liver ATP level was maintained at the control value. CONCLUSIONS: Targeted brain irradiation produced measurable pro- and anti-inflammatory cytokine changes in the systemic circulation. GPC supplementation provides significant protection against irradiation-induced peripheral pro-inflammatory activation and ATP depletion.
Asunto(s)
Citocinas/sangre , Glicerilfosforilcolina/administración & dosificación , Hipocampo/efectos de la radiación , Inflamación/sangre , Inflamación/prevención & control , Traumatismos por Radiación/sangre , Traumatismos por Radiación/prevención & control , Animales , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Masculino , Tolerancia a Radiación/efectos de la radiación , Protectores contra Radiación/administración & dosificación , Radioterapia Conformacional/efectos adversos , Ratas , Ratas Sprague-DawleyRESUMEN
This study was designed to follow the time course of inflammatory activation in a rodent model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis. We hypothesized that oral phosphatidylcholine (PC) pretreatment regimens may influence leukocyte-mediated microcirculatory reactions in this condition. In series I, Wistar rats were monitored 1 day after colitis induction (n = 24), and in series II (n = 24) on day 6 following a TNBS enema. The PC-pretreated animals received a 2% PC-enriched diet for 6 days before the TNBS enema (series I), or for 3 days before and 3 days after TNBS treatment (series II). The macrohemodynamics, serosal microcirculation (visualized by intravital videomicroscopy), colonic xanthine oxidoreductase, myeloperoxidase and nitric oxide end products, and changes in proinflammatory cytokine levels in plasma were measured. The mucosal structural injury was monitored in vivo by means of confocal laser scanning endomicroscopy. The TNBS enema induced a systemic hyperdynamic circulatory reaction with increased serosal capillary blood flow and significantly elevated colonic inflammatory enzyme activities, levels of nitric oxide production, and cytokine concentrations. Acute colitis caused disruption of the capillary network, whereas the morphologic damage was less severe in series II. The PC pretreatment protocols led to significant decreases in the serosal hyperemic reaction, the cytokine levels, and the inflammatory enzyme activities. The objective signs of tissue damage were reduced in both series, and the number of mucus-producing goblet cells in the resolving phase of colitis was increased. Dietary PC efficiently decreases the cytokine-mediated progression of inflammatory events and preserves the microvascular structure in the large intestine.
Asunto(s)
Colitis/dietoterapia , Suplementos Dietéticos , Fosfatidilcolinas/administración & dosificación , Animales , Colitis/patología , Colon/irrigación sanguínea , Colon/enzimología , Colon/patología , Hemodinámica/fisiología , Interleucina-6/metabolismo , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Masculino , Microcirculación/fisiología , Óxido Nítrico/metabolismo , Peroxidasa/metabolismo , Fosfatidilcolinas/farmacología , Distribución Aleatoria , Ratas , Ratas Wistar , Ácido Trinitrobencenosulfónico/toxicidad , Factor de Necrosis Tumoral alfa/metabolismo , Xantina Deshidrogenasa/metabolismoRESUMEN
Our goal was to characterize the neuroprotective properties of orally administered phosphatidylcholine (PC) in a rodent model of systemic inflammation. Sprague-Dawley rats were killed at 3 h, 1 day, 3 days, or 7 days after i.p. administration of lipopolysaccharide (LPS) to determine the plasma levels of tumor necrosis factor α (TNF-α) and interleukin 6 cytokines. The control group and one group of LPS-treated animals were nourished with standard laboratory chow, whereas another LPS-treated group received a special diet enriched with 1% PC for 5 days before the administration of LPS and thereafter during the 7-day observation period. Immunohistochemistry was performed to visualize the bromodeoxyuridine and doublecortin-positive neuroprogenitor cells and Iba1-positive microglia in the hippocampus, whereas the degree of mucosal damage was evaluated on ileal and colon biopsy samples after hematoxylin-eosin staining. The activities of proinflammatory myeloperoxidase and xanthine-oxidoreductase and the tissue nitrite/nitrate (NOx) level were additionally determined, and the cognitive functions were monitored via Morris water maze testing. The inflammatory challenge transiently increased the hippocampal NOx level and led to microglia accumulation and decreased neurogenesis. The intestinal damage, mucosal myeloperoxidase, xanthine-oxidoreductase, and NOx changes were less pronounced, and long-lasting behavioral alterations were not observed. Phosphatidylcholine pretreatment reduced the plasma TNF-α and hippocampal NOx changes and prevented the decreased neurogenesis. These data demonstrated the relative susceptibility of the brain to the consequences of transient peripheral inflammatory stimuli. Phosphatidylcholine supplementation did not reduce the overall extent of peripheral inflammatory activation, but efficiently counteracted the disturbed hippocampal neurogenesis by lowering circulating TNF-α concentrations.