RESUMEN
BACKGROUND: The goal of this study was to investigate whether exogenous offer of L-arginine (LARG) modulates the gene expression of intestinal dysfunction caused by ischemia and reperfusion. METHODS: Eighteen Wistar-EPM1 male rats (250-300 g) were anesthetized and subjected to laparotomy. The superior mesenteric vessels were exposed, and the rats were randomized into 3 groups (n = 6): the control group (CG), with no superior mesenteric artery interruption; the ischemia/reperfusion group (IRG), with 60 minutes of ischemia and 120 minutes of reperfusion and saline injections; and the L-arginine group (IRG + LARG), with L-arginine injected in the femoral vein 5 minutes before ischemia, 5 minutes after reperfusion, and after 55 minutes of reperfusion. The total RNA was extracted and purified from samples of the small intestine. The concentration of each total RNA sample was determined by using spectrophotometry. The first-strand complementary DNA (cDNA) was synthesized in equal amounts of cDNA and the Master Mix SYBR Green qPCR Mastermix (SABiosciences, a Qiagen Company, Frederick, Md). Amounts of cDNA and Master Mix SYBR Green qPCR Mastermix were distributed to each well of the polymerase chain reaction microarray plate containing the predispensed gene-specific primer sets for Bax and Bcl2. Each sample was evaluated in triplicate, and the Student t test was applied to validate the homogeneity of each gene expression reaction (P < .05). RESULTS: The gene expression of Bax in IRG (+1.48) was significantly higher than in IRG-LARG (+9.69); the expression of Bcl2L1 in IRG (+1.01) was significantly higher than IRG-LARG (+22.89). CONCLUSIONS: The apoptotic cell pathway of 2 protagonists showed that LARG improves the gene expression of anti-apoptotic Bcl2l1 (Bcl2-like 1) more than the pro-apoptotic Bax (Bcl2-associated X protein).
Asunto(s)
Arginina/farmacología , Intestino Delgado/irrigación sanguínea , Intestino Delgado/metabolismo , Isquemia/metabolismo , Daño por Reperfusión/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Animales , Apoptosis , Intestino Delgado/patología , Isquemia/complicaciones , Isquemia/patología , Masculino , Arteria Mesentérica Superior , ARN Mensajero/genética , ARN Mensajero/metabolismo , Distribución Aleatoria , Ratas , Ratas Wistar , Daño por Reperfusión/etiología , Daño por Reperfusión/patología , Proteína X Asociada a bcl-2/genéticaRESUMEN
BACKGROUND: This study evaluated the morphology of the rat liver when hyperbaric oxygen (HBO) was used at various stages of ischemia and reperfusion. METHODS: Thirty-two male Wistar rats, subjected to 30 minutes of hepatic ischemia and 30 minutes of reperfusion, were randomly assigned as follows: GIR (n = 8), control without HBO; GHBO/I (n = 8), in which HBO was applied only during ischemia; GHBO/R (n = 8), HBO only during reperfusion; and GHBO/IR (n = 8), HBO during both ischemia and reperfusion. Feasibility scores of hepatocytes were determined by assessing 8 items related to liver injury. RESULTS: The histologic injury score of the hepatic specimens was significantly lower in the GHBO/I group (79.0 ± 0.1) compared with the GIR group (135.0 ± 0.1). HBO was not effective when applied during reperfusion (GHBO/R, 151.3 ± 0.1) or during the ischemia plus reperfusion period (GHBO/IR, 131.0 ± 0.1). The sum was significantly higher (P < .05) in HBO-treated animals during the reperfusion period (ie, in the GHBO/R group compared with any of the other groups). CONCLUSIONS: A favorable effect was obtained when HBO was administered early during ischemia. HBO given in later periods of reperfusion was associated with a more severe sum index percentage of liver damage.
Asunto(s)
Oxigenoterapia Hiperbárica/métodos , Hepatopatías/terapia , Hígado/irrigación sanguínea , Oxígeno/metabolismo , Daño por Reperfusión/terapia , Animales , Modelos Animales de Enfermedad , Precondicionamiento Isquémico , Hígado/patología , Hepatopatías/metabolismo , Hepatopatías/patología , Masculino , Ratas , Ratas Wistar , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patologíaRESUMEN
The aim of this study was evaluate the beta blocker atenolol (AT) and ischemic preconditioning (IPC) strategies for tissue protection against systemic effects of intestinal ischemia (I) and reperfusion (R) injury. Forty-two rats were pretreated with AT (1.5 mg · kg(-1)), 0.9% saline solution (SS; 0.1 mL), or IPC and then subjected to prolonged occlusion of the superior mesenteric artery for 60 minutes leading to I followed or not by 120 minutes of R, according to the group. For IPC, 5 minutes of I prior to 10 minutes of R were established. After this process of I or I-R, the right lung of each animal was adequately prepared for staining with hematoxylin and eosin and subsequent histologic analysis for quantification of inflammatory infiltrate was done. The left lung was frozen and prepared for assessment of oxidative stress by the quantification of thiobarbituric acid-reactivity substances (TBARS). Histologic analysis showed an important inflammatory infiltrate in the I-R + SS (I-R + SS = 4.5), which was significantly (P < .05) reduced by IPC (I-R + IPC = 3.0) or AT (I-R + AT = 3.0). Likewise, the TBARS levels were decreased by both strategies (I-R + SS = 0.63; I-R + IPC = 0.23; I-R + AT = 0.38; P < .05). Our results showed that AT and IPC attenuate pulmonary lesions caused by intestinal I and R process.
Asunto(s)
Atenolol/farmacología , Intestinos/irrigación sanguínea , Precondicionamiento Isquémico/métodos , Lesión Pulmonar/prevención & control , Pulmón/irrigación sanguínea , Daño por Reperfusión/prevención & control , Antagonistas de Receptores Adrenérgicos beta 1/farmacología , Animales , Modelos Animales de Enfermedad , Lesión Pulmonar/etiología , Masculino , Ratas , Ratas Wistar , Daño por Reperfusión/complicacionesRESUMEN
To study the role of heparin and ischemic preconditioning (IPC) in cardiac injury after intestinal ischemia (I) and reperfusion (R), 54 rats underwent 60 minutes of I, which was produced by occlusion of the superior mesenteric artery, and/or 120 minutes of R. The IPC group had the I procedure stimulation for 5 minutes and R for 10 minutes. The control group was subjected to sham surgery only, and the other groups were injected with saline solution (SS; 0.1 mL) or heparin (100 IU/kg) via the inferior cava vein 5 minutes before I and 5 minutes before R and 55 minutes after the R begins in I-R groups. In all animals, cardiac samples were stained with hematoxylin and eosin for optical microscopy analysis, and other sample was processed for lipid peroxidation determination. In I-R groups, both heparin and IPC showed significant protection compared to the SS group; conversely, in animals subjected only to I, no protection was observed. Moreover, when heparin was associated with IPC, I-R protection was compromised and the ischemic injury increased. Data showed that IPC and heparin attenuated cardiac dysfunction caused by intestinal I and I-R, but when used in association did not show beneficial effects.
Asunto(s)
Cardiomiopatías/prevención & control , Heparina/uso terapéutico , Intestinos/irrigación sanguínea , Precondicionamiento Isquémico/métodos , Daño por Reperfusión/prevención & control , Animales , Anticoagulantes/uso terapéutico , Cardiomiopatías/etiología , Modelos Animales de Enfermedad , Masculino , Ratas , Ratas Wistar , Daño por Reperfusión/complicacionesRESUMEN
Ionotropically crosslinked alginate beads suffer generally from poor drug loading, poor stability in biorelevant media and hence fast (i.e. uncontrolled) drug release profiles. Therefore, the present work aims at addressing these drawbacks by enhancing the stability of these metal ion-crosslinked alginate complexes via the incorporation of terephthalic acid which is proposed to act as a bridging crosslinking aid. In addition to the effect of terephthalic acid, we investigated the effect of curing temperature (4, 25 and 40 degrees C) and curing cross-linking metal ions (zinc, calcium and aluminum) on the characteristics of the resulting beads, i.e., drug loading and release profiles. Methylene blue (MB) was used as loaded drug model. The resulting beads were chemically and physically probed using infrared spectroscopy and differential scanning calorimetry. Interestingly, all prepared alginate-terephthalate beads (i.e., cured with zinc, calcium and aluminum) illustrated higher MB loadings and accessed controlled release profiles compared to their corresponding terephthalate-free alginate counterparts. Calcium-crosslinked alginate-terephthalate beads illustrated enteric release behavior regardless of their curing temperature. On the other hand, zinc-crosslinked alginate-terephthalate beads accessed enteric-like release profiles when only cured at 40 degrees C. However, aluminum-crosslinked alginate-terephthalate beads yielded interesting zero order release profiles regardless of their curing temperatures.
Asunto(s)
Alginatos/química , Preparaciones de Acción Retardada , Ácidos Ftálicos/química , Aluminio/química , Rastreo Diferencial de Calorimetría , Química Farmacéutica , Colorantes/farmacocinética , Reactivos de Enlaces Cruzados , Portadores de Fármacos , Azul de Metileno/farmacocinética , Solubilidad , Espectrofotometría Infrarroja , Espectrofotometría Ultravioleta , Zinc/químicaRESUMEN
To study whether treatment with heparin (HEP) attenuates intestinal dysfunction caused by ischemia (I) and reperfusion (R), rats were treated with HEP (100 U/kg intravenously) or saline solution (SS) before I (60 min), which was produced by occlusion of the superior mesenteric artery, and R (120 min). After I or I/R, we mounted 2-cm jejunal segment in an organ bath to study neurogenic contractions stimulated by electrical pulses or KCl, using a digital recording system. Thin jejunal slices were stained with hematoxylin and eosin for optical microscopy. Compared with the sham group, jejunal contractions were similar in the I + HEP and the I/R + HEP groups, but reduced in the I + SS and the I/R + SS groups. The jejunal enteric nerves were damaged in the I + SS and the I/R + SS, but not in the I + HEP and the I/R + HEP cohorts. These results suggested that HEP attenuated intestinal dysfunction caused by I and I/R.
Asunto(s)
Fármacos Gastrointestinales/farmacología , Heparina/farmacología , Yeyuno/irrigación sanguínea , Yeyuno/efectos de los fármacos , Daño por Reperfusión/prevención & control , Animales , Citoprotección , Modelos Animales de Enfermedad , Estimulación Eléctrica , Sistema Nervioso Entérico/efectos de los fármacos , Sistema Nervioso Entérico/fisiopatología , Motilidad Gastrointestinal/efectos de los fármacos , Yeyuno/inervación , Yeyuno/patología , Yeyuno/fisiopatología , Masculino , Cloruro de Potasio/farmacología , Ratas , Ratas Wistar , Daño por Reperfusión/patología , Daño por Reperfusión/fisiopatologíaRESUMEN
To study whether ischemic preconditioning (IPC) attenuated intestinal dysfunction caused by ischemia (I) and reperfusion (R), rats were underwent 60 minutes of I which was produced by occlusion of the superior mesenteric artery, and/or 120 minutes R. The IPC group had the I procedure previously stimulated for 5 minutes and the R for 10 minutes. IPC and sham groups were injected with saline solution (SS) via the femoral vein 5 minutes before the I and R, and for R. After I or I/R, 2-cm jejunal segments were mounted in an organ bath to study neurogenic contractions stimulated by electrical pulses or KCl using a digital recording system. Thin jejunal slices were stained with hematoxylin and eosin for optical microscopy. Compared with the sham group, jejunal contractions were similar in the IPC + I and the IPC + I/R groups, but reduced in the I + SS and the I/R + SS groups. The jejunal enteric nerves were damaged in the I + SS and the I/R + SS groups, but not in the IPC groups. These results suggested that ischemic preconditioning attenuated intestinal dysfunction caused by I and I/R.
Asunto(s)
Precondicionamiento Isquémico , Yeyuno/irrigación sanguínea , Daño por Reperfusión/prevención & control , Animales , Modelos Animales de Enfermedad , Estimulación Eléctrica , Sistema Nervioso Entérico/fisiopatología , Motilidad Gastrointestinal , Yeyuno/efectos de los fármacos , Yeyuno/inervación , Yeyuno/patología , Yeyuno/fisiopatología , Masculino , Cloruro de Potasio/farmacología , Ratas , Ratas Wistar , Daño por Reperfusión/patología , Daño por Reperfusión/fisiopatologíaRESUMEN
To examine whether treatment with L-arginine (ARG), a substrate of nitric oxide biosynthesis, attenuated intestinal dysfunction caused by ischemia (I) and reperfusion (R), we treated rats with ARG (100 mg/kg intravenously) or saline solution (SS) before 60 minutes of I produced by occlusion of the superior mesenteric artery and/or during 120 minutes of R. After I or I/R, we isolated 2-cm jejunal segments for mounting in an organ bath to study neurogenic contractions stimulated by electrical pulses or KCl with the use of a digital recording system. Thin jejunal slices were stained with hematoxylin and eosin for optical microscopy. Jejunal contractions were similar in the sham and I+ARG, but reduced in I+SS, I/R+SS, and I/R+ARG groups. Jejunal enteric nerves were damaged in I+SS, IR+SS, and IR+ARG, but not in the I+ARG group, suggesting that ARG attenuate intestinal dysfunctions due to I but not to R.
Asunto(s)
Arginina/farmacología , Fármacos Gastrointestinales/farmacología , Yeyuno/irrigación sanguínea , Yeyuno/efectos de los fármacos , Daño por Reperfusión/tratamiento farmacológico , Animales , Citoprotección , Modelos Animales de Enfermedad , Estimulación Eléctrica , Sistema Nervioso Entérico/efectos de los fármacos , Sistema Nervioso Entérico/fisiopatología , Motilidad Gastrointestinal/efectos de los fármacos , Yeyuno/inervación , Yeyuno/patología , Yeyuno/fisiopatología , Masculino , Cloruro de Potasio/farmacología , Ratas , Ratas Wistar , Daño por Reperfusión/patología , Daño por Reperfusión/fisiopatologíaRESUMEN
To study whether treatment with adenosine (ADO), an agonist of adenosine receptors, attenuates intestinal dysfunction caused by ischemia (I) and reperfusion (R), we treated rats with ADO (15 mg/kg or saline solution (SS) intravenously before 60 minutes occlusion of the superior mesenteric artery (I) and/or 120 minutes after its release (R). After I or I/R, isolated jejunal segments (2 cm) were mounted in an organ bath to study nerve-mediated contractions stimulated by electrical pulses or KCI with the use of a digital recording system. Thin jejunal slices were stained with hematoxylin and eosin for optical microscopy. Compared with the sham group, jejunal contractions were reduced in I+SS and IR+SS but similar after treatment with ADO (I+ADO and IR+ADO groups). We concluded that rat jejunal enteric nerves were damaged in I+SS and IR+SS but not in the I+ADO and IR+ADO groups. These results suggested that ADO attenuated intestinal dysfunction due to I and R.
Asunto(s)
Adenosina/farmacología , Fármacos Gastrointestinales/farmacología , Yeyuno/irrigación sanguínea , Yeyuno/efectos de los fármacos , Daño por Reperfusión/prevención & control , Animales , Citoprotección , Modelos Animales de Enfermedad , Estimulación Eléctrica , Sistema Nervioso Entérico/efectos de los fármacos , Sistema Nervioso Entérico/fisiopatología , Motilidad Gastrointestinal/efectos de los fármacos , Yeyuno/inervación , Yeyuno/patología , Yeyuno/fisiopatología , Cloruro de Potasio/farmacología , Ratas , Ratas Wistar , Daño por Reperfusión/patología , Daño por Reperfusión/fisiopatologíaRESUMEN
To study whether treatment with the beta-blocker atenolol (AT) attenuates intestinal dysfunction caused by ischemia (I) and reperfusion (R), rats were treated with AT (1.5 mg · kg(-1), intravenously) or saline solution (SS) prior to I (60 minutes), which was produced by occlusion of the superior mesenteric artery, and/or R (120 minutes). After I or I/R, 2-cm jejunal segments were mounted in an organ bath to study neurogenic contractions stimulated by electrical pulses or KCl using a digital recording system. Thin jejunal slices were stained with hematoxylin and eosin for optical microscopy analysis. Compared to the sham group, jejunal contractions were similar in the I + AT and the I/R + AT groups, but reduced in the I + SS and the I/R + SS groups. The jejunal enteric nerves were damaged in the I + SS and the I/R + SS groups, but not in the I + AT and the I/R + AT. These results suggest that AT may attenuate intestinal dysfunction caused by I and I/R.
Asunto(s)
Antagonistas de Receptores Adrenérgicos beta 1/farmacología , Atenolol/farmacología , Fármacos Gastrointestinales/farmacología , Yeyuno/irrigación sanguínea , Yeyuno/efectos de los fármacos , Daño por Reperfusión/prevención & control , Animales , Citoprotección , Modelos Animales de Enfermedad , Estimulación Eléctrica , Sistema Nervioso Entérico/efectos de los fármacos , Sistema Nervioso Entérico/fisiopatología , Motilidad Gastrointestinal/efectos de los fármacos , Yeyuno/inervación , Yeyuno/patología , Yeyuno/fisiopatología , Masculino , Cloruro de Potasio/farmacología , Ratas , Ratas Wistar , Daño por Reperfusión/patología , Daño por Reperfusión/fisiopatologíaRESUMEN
BACKGROUND: Dysfunction of the liver after transplantation may be related to the graft size and ischemia/reperfusion (I/R) injury. N-Acetylcysteine (NAC) exerts beneficial effects on livers undergoing ischemia reperfusion. We sought to evaluate NAC modulation on reduced livers associated with I/R injury. METHODS: Male C57BL/6 mice of 8 weeks of age were divided into groups: 50% hepatectomy (G-Hep); NAC (G-Hep + NAC [150 mg/kg]) via vena cava 15 minutes before hepatectomy; ischemia (G-Hep + IR); NAC with hepatectomy (G-IR + Hep + Nac); and IR using 30 minutes selective hepatic occlusion and reperfusion for 24 hours. After 24 hours, the remaining liver was removed, for staining with hematoxylin and eosin or labeling by proliferating cell nuclear antigen. Blood was collected for biochemical evaluations. Significance was considered for P ≤ .05. RESULTS: Aspartate aminotransferase was high in all studied groups reflecting the hepatectomy and intervention. injuries. However, when assessing alanine aminotransferase, which depicts liver function, induction of IR promoted a greater increase than hepatectomy (P = .0003). NAC decreased ALT activity in all groups, even in association with I/R (P < .05), reflecting a modulation of the injury. Necrosis resulting from IR was mitigated by NAC. The experimental model of 50% reduced live promoted regeneration of the hepatic remnant, which was accentuated by NAC, according to the total number of hepatocytes and PCNA values. CONCLUSION: NAC preserved the remnant liver in mice and stimulates regeneration even after IR injury.
Asunto(s)
Acetilcisteína/farmacología , Proliferación Celular/efectos de los fármacos , Hepatectomía , Regeneración Hepática/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/cirugía , Daño por Reperfusión/tratamiento farmacológico , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Biomarcadores/sangre , Biomarcadores/metabolismo , Citoprotección , Modelos Animales de Enfermedad , Inmunohistoquímica , Hígado/irrigación sanguínea , Hígado/metabolismo , Hígado/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Necrosis , Antígeno Nuclear de Célula en Proliferación/metabolismo , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Factores de TiempoRESUMEN
To study whether treatment with L-arginine (ARG), a substrate of nitric oxide biosynthesis, attenuates intestinal dysfunction caused by ischemia (I) and reperfusion (R), rabbits treated with ARG (100 mgxkg(-1), intravenously) or saline solution (SS) prior to I (60 minutes) by occlusion of superior mesenteric artery and/or during R (120 minutes). After I or I/R, 2-cm jejunal segments were isolated and mounted in an organ bath to study of neurogenic contractions stimulated by electrical pulses or KCl using a digital recording system. Thin jejunal slices were stained (hematoxylin and eosin) for analysis by optical microscopy. Compared to the sham group, jejunal contractions were similar in I + ARG, but reduced in I + SS, I/R + SS, and I/R + ARG groups. The jejunal enteric nerves were damaged in I + SS, I/R + SS, and I/R + ARG, but not in I + ARG group, suggesting that ARG can attenuate intestinal dysfunctions due to I, but not to R.
Asunto(s)
Arginina/farmacología , Intestinos/irrigación sanguínea , Óxido Nítrico/biosíntesis , Daño por Reperfusión/prevención & control , Animales , Arginina/uso terapéutico , Circulación Sanguínea , Vena Femoral/fisiología , Motilidad Gastrointestinal/efectos de los fármacos , Motilidad Gastrointestinal/fisiología , Isquemia/fisiopatología , Yeyuno/irrigación sanguínea , Yeyuno/efectos de los fármacos , Yeyuno/patología , Arteria Mesentérica Superior/fisiología , Conejos , Reperfusión/efectos adversos , Daño por Reperfusión/fisiopatologíaRESUMEN
To study whether treatment with the beta-blocker atenolol (AT) attenuates intestinal dysfunction caused by ischemia (I) and reperfusion (R), rabbits were treated with AT (1 mg.kg(-1), introvenously) or saline solution (SS) prior to I (60 minutes), which was produced by occlusion of the superior mesenteric artery, and/or R (120 minutes). After I or I/R, 2-cm jejunal segments were mounted in an organ bath to study neurogenic contractions stimulated by electrical pulses or KCl using a digital recording system. Thin jejunal slices were stained hematoxylin and eosin for analysis by optical microscopy. Compared to the sham group, the jejunal contractions were similar in the I + AT and the I/R + AT groups, but reduced in the I + SS and the I/R + SS groups. The jejunal enteric nerves were damaged in the I + SS and the I/R + SS groups, but not in the I + AT and the I/R + AT. These results suggest that AT may attenuate intestinal dysfunction caused by I and I/R.
Asunto(s)
Atenolol/uso terapéutico , Enfermedades Intestinales/tratamiento farmacológico , Intestinos/irrigación sanguínea , Yeyuno/fisiología , Daño por Reperfusión/tratamiento farmacológico , Animales , Circulación Sanguínea , Estimulación Eléctrica , Enfermedades Intestinales/etiología , Yeyuno/irrigación sanguínea , Yeyuno/efectos de los fármacos , Masculino , Arteria Mesentérica Superior/fisiología , Contracción Muscular/efectos de los fármacos , Contracción Muscular/fisiología , Cloruro de Potasio/farmacología , ConejosRESUMEN
To study if the treatment with adenosine (ADO), an agonist of adenosine receptors, attenuates intestinal dysfunction caused by ischemia (I) and reperfusion (R), we treated rabbits with ADO (15 mg x kg(-1), intravenously) or saline solution (SS) to I (60 minutes) before occlusion of superior mesenteric artery and/or R (120 min). After I or I/R, isolated jejunal segments (2 cm) were mounted in an organ bath to study nerve-mediated contractions stimulated by electrical pulses or KCl using a digital recording system. Thin jejunal slices were stained (hematoxylin and eosin) for analysis by optical microscopy. Compared to the sham group, the jejunal contractions were similar in I + ADO, but reduced in I + SS, I/R + SS, and I/R + ADO groups. We concluded that the jejunal enteric nerves were damaged in I + SS, I/R + SS, and I/R + ADO, but not in I + ADO group. These results suggested that ADO attenuated intestinal dysfunction due to I, but not to R.
Asunto(s)
Adenosina/farmacología , Intestinos/irrigación sanguínea , Daño por Reperfusión/tratamiento farmacológico , Animales , Circulación Sanguínea , Estimulación Eléctrica , Vena Femoral/efectos de los fármacos , Vena Femoral/fisiología , Yeyuno/irrigación sanguínea , Yeyuno/efectos de los fármacos , Yeyuno/fisiología , Masculino , Arteria Mesentérica Superior/fisiología , Contracción Muscular/efectos de los fármacos , Contracción Muscular/fisiología , Cloruro de Potasio/farmacología , Agonistas del Receptor Purinérgico P1 , Conejos , Cloruro de Sodio/farmacologíaRESUMEN
To study whether treatment with L-nitro-arginine methyl ester (L-NAME), an inhibitor of nitric oxide biosynthesis, attenuates intestinal dysfunction caused by ischemia (I) and/or reperfusion (R), rabbits were treated with L-NAME (15 mgxkg(-1), intervenously) or saline olution (SS) prior to I (60 minutes) induced by occlusion of superior mesenteric artery and/or R (120 minutes). After I or I/R, isolated jejunal segments (2 cm) were mounted in an organ bath to study nerve-mediated contractions stimulated by electrical pulses or KCI using a digital recording system. Thin jejunal slices were stained (hematoxylin and eosin) for analysis by optical microscopy. Compared with a sham group, the jejunal contractions were similar in the I/R + L-NAME, but reduced in I + SS, I/R + SS, and I + L-NAME groups. The jejunal enteric nerves were damaged in the I + SS, I/R + SS, and I + L-NAME cohorts, but not among the I/R + L-NAME cohort. These results suggested that L-NAME attenuated intestinal dysfunction caused by R but not by I.
Asunto(s)
Motilidad Gastrointestinal/efectos de los fármacos , Enfermedades Intestinales/prevención & control , NG-Nitroarginina Metil Éster/farmacología , Daño por Reperfusión/prevención & control , Daño por Reperfusión/fisiopatología , Animales , Estimulación Eléctrica , Isquemia/fisiopatología , Yeyuno/efectos de los fármacos , Yeyuno/inervación , Yeyuno/fisiología , Masculino , Contracción Muscular/efectos de los fármacos , Contracción Muscular/fisiología , Conejos , Cloruro de Sodio/farmacologíaRESUMEN
To study whether treatment with 5'-adenosine triphosphate (ATP), an agonist of P2 purine receptors, attenuated intestinal dysfunction caused by ischemia (I) and/or reperfusion (R), rabbits were treated with ATP (15 mgxkg(-1), intravenously) or saline solution (SS) 60 minutes before I by occlusion of the superior mesenteric artery and/or R (120 minutes). After I or I/R isolated 2-cm jejunal segments were mounted in an organ bath to study nerve-mediated contractions stimulated by electrical pulses or KCl using a digital recording system. Thin jejunal slices were stained (hematoxylin and eosin) for optical microscopy. Compared to a sham group, the jejunal contractions were similar to sham hosts among I + ATP, but reduced in I + SS, I/R + SS, and I/R + ATP groups. The jejunal-enteric nerves were damaged in I + SS, I/R + SS, and I/R + ATP, but not the I + ATP group. These results suggested that ATP attenuated intestinal dysfunction produced by I, but not that caused by R.
Asunto(s)
Adenosina Trifosfato/farmacología , Intestinos/irrigación sanguínea , Isquemia/fisiopatología , Yeyuno/irrigación sanguínea , Daño por Reperfusión/fisiopatología , Animales , Circulación Sanguínea/efectos de los fármacos , Circulación Sanguínea/fisiología , Isquemia/tratamiento farmacológico , Yeyuno/efectos de los fármacos , Yeyuno/inervación , Masculino , Arteria Mesentérica Superior/efectos de los fármacos , Arteria Mesentérica Superior/fisiopatología , Conejos , Cloruro de Sodio/farmacologíaRESUMEN
BACKGROUND: Hard-to-heal wounds present a major medical problem. The anticonvulsant drug phenytoin has been shown to have prohealing effects in various types of wounds. In this study we evaluated the effect of phenytoin on some phases of wound healing in a rat excision wound model. METHODS: A total of 98 adult male Wistar rats were used in this study. The effect of phenytoin ointment on the time for complete wound closure, as well as its biochemical and histological effects were evaluated in an excision wound. In addition, mechanical effect of phenytoin was evaluated in an incision wound rat model. RESULTS: Phenytoin hastened the healing and increased protein and hydroxyproline contents as well as histological collagenization of excision wounds. In addition, it increased the tensile strength in incision wound model. CONCLUSION: This study is the first to profile in detail the effects of phenytoin on morphology and biochemistry of excision wounds. We have shown that phenytoin not only shortens the time for wound healing but also improves the quality of the healing tissue. These effects are sought for in various clinical settings in which unaided healing is inconveniently prolonged or where the forming scar is not fully developed, allowing relapse of the wound.
Asunto(s)
Colágeno/metabolismo , Fenitoína/farmacología , Cicatrización de Heridas/efectos de los fármacos , Heridas y Lesiones/patología , Animales , Fenómenos Biomecánicos , Tejido de Granulación/efectos de los fármacos , Hidroxiprolina/metabolismo , Masculino , Pomadas , Vaselina , Proteínas/metabolismo , Ratas , Ratas Wistar , Resistencia a la TracciónRESUMEN
In this work, we evaluate the effects of adenosine 5' triphosphate (ATP) on hepatic lesions caused by ischemia/reperfusion (I/R) in liver rabbit. Rabbits were pretreated with ATP (15 mg/kg IV) or saline solution 0.9% (SS), before the hepatic I/R procedure. We evaluated the effects of ATP on hepatic injury before and after I/R. The warm hepatic I/R procedure caused profound acute liver injury, as indicated by elevated serum aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase levels, as well as a high apoptotic cell count. All these changes were attenuate by ATP treatment before the hepatic I/R procedure. These results suggested that ATP exerted protective effects on hepatic I/R lesions in the rabbit. This ATP effect may be related to improved energy metabolism during reperfusion in ischemic livers protecting against functional damage of cellular and subcellular membranes during lipid peroxidation.
Asunto(s)
Hepatopatías/fisiopatología , Purinas/metabolismo , Daño por Reperfusión/fisiopatología , Adenosina Trifosfato/uso terapéutico , Alanina Transaminasa/efectos de los fármacos , Alanina Transaminasa/metabolismo , Animales , Aspartato Aminotransferasas/efectos de los fármacos , Aspartato Aminotransferasas/metabolismo , Isquemia/fisiopatología , L-Lactato Deshidrogenasa/efectos de los fármacos , L-Lactato Deshidrogenasa/metabolismo , Hígado/efectos de los fármacos , Hígado/fisiopatología , Hepatopatías/prevención & control , Masculino , Mitocondrias Hepáticas/efectos de los fármacos , Mitocondrias Hepáticas/metabolismo , Conejos , Daño por Reperfusión/prevención & controlRESUMEN
We evaluated the effects of a substrate in the biosynthesis of nitric oxide (NO)-l-arginine (LARG)-on hepatic lesions caused by ischemia/reperfusion (I/R) injury in rabbit livers. Rabbits were pretreated with LARG (150 mg/kg IV) or saline solution 0.9% (SS) before the hepatic I/R procedure. The effects of LARG on hepatic injury were evaluated before and after I/R. The warm hepatic I/R procedure produced profound acute liver injury, as indicated by elevated values of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactic dehydrogenase (LDH), as well as a high apoptotic cell count. All changes were attenuated by treatment with LARG before the hepatic I/R procedure. These results suggested that LARG produced protective effects on hepatic I/R lesions. This protective effect of LARG was probably associated with blocking generation of superoxide anions during the hepatic I/R procedure.
Asunto(s)
Arginina/uso terapéutico , Hepatopatías/prevención & control , Daño por Reperfusión/prevención & control , Alanina Transaminasa/sangre , Alanina Transaminasa/efectos de los fármacos , Animales , Aspartato Aminotransferasas/sangre , Aspartato Aminotransferasas/efectos de los fármacos , L-Lactato Deshidrogenasa/sangre , L-Lactato Deshidrogenasa/efectos de los fármacos , Circulación Hepática/efectos de los fármacos , Masculino , Óxido Nítrico/metabolismo , Conejos , Daño por Reperfusión/enzimología , Daño por Reperfusión/patología , Vasoconstricción/efectos de los fármacosRESUMEN
Because the role of heparin (HEP) in hepatic ischemia/reperfusion (I/R) injury is still not fully understood, we investigated the effects of treatment with HEP on hepatic I/R injury in rabbits. For I/R procedures, the portal vein and hepatic artery were occluded by a metallic clamp to promote ischemia. The clamp was removed after 30 minutes to allow reperfusion. Rabbits undergoing the I/R procedure were treated with HEP (100 U/kg) or saline solution 0.9% (SS). When compared with levels before I/R, the serum aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase, levels were increased by the hepatic I/R procedure, among rabbits treated with SS or HEP. However, the increase in these enzymes was lower among rabbits treated with HEP. Histologic analysis of hepatic tissue of rabbits undergoing I/R and treated with SS showed marked lesions in the central lobule with significant inflammatory infiltration. In contrast, a significant reduction in lesions caused by I/R was observed in the livers of rabbits treated with HEP. After starting reperfusion, we visualized apoptotic cells with nuclear staining among rabbits submitted to I/R and treated with SS, but not those treated with HEP. These results suggested that HEP was able to attenuate hepatic lesions caused by I/R in the livers of rabbits.