RESUMO
PURPOSE: To evaluate in vivo animal model of cardiac ischemia/reperfusion the cardioprotective activity of pancreatic lipase inhibitor of the orlistat. METHODS: Adult male Wistar rats were anesthetized, placed on mechanical ventilation and underwent surgery to induce cardiac I/R by obstructing left descending coronary artery followed by reperfusion to evaluation of ventricular arrhythmias (VA), atrioventricular block (AVB) and lethality (LET) with pancreatic lipase inhibitor orlistat (ORL). At the end of reperfusion, blood samples were collected for determination of triglycerides (TG), very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL), lactate dehydrogenase (LDH), creatine kinase (CK), and creatine kinase-MB (CK-MB). RESULTS: Treatment with ORL has been able to decrease the incidence of VA, AVB and LET. Besides that, treatment with ORL reduced serum concentrations of CK and LDL, but did not alter the levels of serum concentration of TG, VLDL and HDL. CONCLUSION: The reduction of ventricular arrhythmias, atrioventricular block, and lethality and serum levels of creatine kinase produced by treatment with orlistat in animal model of cardiac isquemia/reperfusion injury suggest that ORL could be used as an efficient cardioprotective therapeutic strategy to attenuate myocardial damage related to acute myocardial infarction.
Assuntos
Cardiotônicos/farmacologia , Lactonas/farmacologia , Infarto do Miocárdio/prevenção & controle , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Animais , Arritmias Cardíacas/prevenção & controle , Bloqueio Atrioventricular/prevenção & controle , Creatina Quinase/sangue , Eletrocardiografia , L-Lactato Desidrogenase/sangue , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Lipoproteínas VLDL/sangue , Masculino , Infarto do Miocárdio/sangue , Traumatismo por Reperfusão Miocárdica/sangue , Orlistate , Distribuição Aleatória , Ratos Wistar , Reprodutibilidade dos Testes , Fatores de Risco , Resultado do Tratamento , Triglicerídeos/sangueRESUMO
Abstract Purpose: To evaluate in vivo animal model of cardiac ischemia/reperfusion the cardioprotective activity of pancreatic lipase inhibitor of the orlistat. Methods: Adult male Wistar rats were anesthetized, placed on mechanical ventilation and underwent surgery to induce cardiac I/R by obstructing left descending coronary artery followed by reperfusion to evaluation of ventricular arrhythmias (VA), atrioventricular block (AVB) and lethality (LET) with pancreatic lipase inhibitor orlistat (ORL). At the end of reperfusion, blood samples were collected for determination of triglycerides (TG), very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL), lactate dehydrogenase (LDH), creatine kinase (CK), and creatine kinase-MB (CK-MB). Results: Treatment with ORL has been able to decrease the incidence of VA, AVB and LET. Besides that, treatment with ORL reduced serum concentrations of CK and LDL, but did not alter the levels of serum concentration of TG, VLDL and HDL. Conclusion: The reduction of ventricular arrhythmias, atrioventricular block, and lethality and serum levels of creatine kinase produced by treatment with orlistat in animal model of cardiac isquemia/reperfusion injury suggest that ORL could be used as an efficient cardioprotective therapeutic strategy to attenuate myocardial damage related to acute myocardial infarction.
Assuntos
Animais , Masculino , Cardiotônicos/farmacologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Lactonas/farmacologia , Infarto do Miocárdio/prevenção & controle , Arritmias Cardíacas/prevenção & controle , Triglicerídeos/sangue , Traumatismo por Reperfusão Miocárdica/sangue , Distribuição Aleatória , Reprodutibilidade dos Testes , Fatores de Risco , Resultado do Tratamento , Ratos Wistar , Creatina Quinase/sangue , Eletrocardiografia , Bloqueio Atrioventricular/prevenção & controle , L-Lactato Desidrogenase/sangue , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Lipoproteínas VLDL/sangue , Infarto do Miocárdio/sangueRESUMO
PURPOSE: To investigate the expression of nitric oxide synthase (NOS) and apoptosis associated with ischemic preconditioning (IPC) and pentoxifylline (PTX) in intestinal ischemia (I) and reperfusion (R) injury. METHODS: Thirty male rats were assigned to 5 groups: (CG), no clamping of the superior mesenteric artery (90 minutes); (IR-SS) saline + ischemia (30 minutes) + reperfusion (60 minutes); (IR-PTX) PTX + ischemia (30 minutes) + reperfusion (60 minutes); (IPC-IR-SS) 5 minutes of ischemia + 5 minutes of reperfusion (IPC) + saline + I(30 minutes)+R(60 minutes); and (IPC-IR-PTX) IPC + PTX + I(30 minutes)+ R(60 minutes). RESULTS: The application of IPC and PTX showed a significantly lower immunohistochemistry reaction for active caspase-3 (P<0.05) compared to IR+SS. The number of cells immunoreactive to BCL-2 was higher in the IR-PTX group (P>0.05). The NOS-2 expression (qRTPCR) in the IR-PTX group (P<0.05) was higher than the values for the IPC+IR-SS and IPC-IR-PTX groups. The NOS-3 expression was significantly upper in the IPC-IR-PTX group than in the CG (P<0.05), the IR-SS (P<0.05) and the IR-PTX (P<0.05) groups. CONCLUSIONS: The BCL-2 and active caspase-3 showed beneficial effects on PTX and IPC. The expression of NOS-2 and NOS-3 in the IPC and IPC-PTX groups showed no synergistic effect.
Assuntos
Apoptose/efeitos dos fármacos , Enteropatias/prevenção & controle , Intestinos/irrigação sanguínea , Precondicionamento Isquêmico , Óxido Nítrico Sintase/metabolismo , Pentoxifilina/uso terapêutico , Animais , Apoptose/fisiologia , Modelos Animais de Doenças , Humanos , Imuno-Histoquímica , Enteropatias/enzimologia , Intestinos/patologia , Masculino , RNA Mensageiro/análise , Ratos , Ratos Wistar , Vasodilatadores/uso terapêuticoRESUMO
Abstract Purpose: To investigate the expression of nitric oxide synthase (NOS) and apoptosis associated with ischemic preconditioning (IPC) and pentoxifylline (PTX) in intestinal ischemia (I) and reperfusion (R) injury. Methods: Thirty male rats were assigned to 5 groups: (CG), no clamping of the superior mesenteric artery (90 minutes); (IR-SS) saline + ischemia (30 minutes) + reperfusion (60 minutes); (IR-PTX) PTX + ischemia (30 minutes) + reperfusion (60 minutes); (IPC-IR-SS) 5 minutes of ischemia + 5 minutes of reperfusion (IPC) + saline + I(30 minutes)+R(60 minutes); and (IPC-IR-PTX) IPC + PTX + I(30 minutes)+ R(60 minutes). Results: The application of IPC and PTX showed a significantly lower immunohistochemistry reaction for active caspase-3 (P<0.05) compared to IR+SS. The number of cells immunoreactive to BCL-2 was higher in the IR-PTX group (P>0.05). The NOS-2 expression (qRTPCR) in the IR-PTX group (P<0.05) was higher than the values for the IPC+IR-SS and IPC-IR-PTX groups. The NOS-3 expression was significantly upper in the IPC-IR-PTX group than in the CG (P<0.05), the IR-SS (P<0.05) and the IR-PTX (P<0.05) groups. Conclusions: The BCL-2 and active caspase-3 showed beneficial effects on PTX and IPC. The expression of NOS-2 and NOS-3 in the IPC and IPC-PTX groups showed no synergistic effect.
Assuntos
Humanos , Animais , Masculino , Ratos , Pentoxifilina/uso terapêutico , Apoptose/efeitos dos fármacos , Óxido Nítrico Sintase/metabolismo , Precondicionamento Isquêmico , Enteropatias/prevenção & controle , Intestinos/irrigação sanguínea , Vasodilatadores/uso terapêutico , RNA Mensageiro/análise , Imuno-Histoquímica , Ratos Wistar , Apoptose/fisiologia , Modelos Animais de Doenças , Enteropatias/enzimologia , Intestinos/patologiaRESUMO
PURPOSE:: To investigate the role of ischemic preconditioning (IPC) and pentoxifylline (PTX) in intestinal mucosa ischemia/reperfusion injury (IR). METHODS:: Thirty rats were assigned to 5 groups (N=6): (CG): no clamping of the superior mesenteric artery (90 min.); (IR-SS): saline + ischemia (30 min.) + reperfusion (60 min.); (IR-PTX): PTX + ischemia (30min.) + reperfusion (60 min.); (IPC-IR-SS): 5 min. of ischemia + 5 minutes of reperfusion (IPC) + saline + ischemia (30 min.) + reperfusion (60 min.); (IPC-IR-PTX ): 5 min. of ischemia + 5 min. of reperfusion (IPC) + PTX + 30 min. of I + 60 minutes of R. RESULTS:: The IR-PTX, IPC-IR-SS and IPC-IR-PTX groups had significantly lower scores of mucosa damage than the IR-SS group. IR-PTX group showed higher scores than the IPC-IR-PTX group, in accordance with the hypothesis of a favorable effect of IPC alone or in association with PTX. Additionally, IPC-IR-SS had a higher damage score than the IPC-IR-PTX. The villi height and crypt depth were similar in all groups. The villi height in the IR-SS was significantly lower. CONCLUSION:: Ischemic preconditioning or pentoxifylline alone protect the intestinal mucosa from ischemia/reperfusion injury. However, they do not have a synergistic effect when applied together.
Assuntos
Intestinos/irrigação sanguínea , Intestinos/patologia , Pentoxifilina/uso terapêutico , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/prevenção & controle , Vasodilatadores/uso terapêutico , Animais , Modelos Animais de Doenças , Precondicionamento Isquêmico , Masculino , Ratos , Ratos Wistar , Traumatismo por Reperfusão/tratamento farmacológicoRESUMO
Abstract Purpose: To investigate the role of ischemic preconditioning (IPC) and pentoxifylline (PTX) in intestinal mucosa ischemia/reperfusion injury (IR). Methods: Thirty rats were assigned to 5 groups (N=6): (CG): no clamping of the superior mesenteric artery (90 min.); (IR-SS): saline + ischemia (30 min.) + reperfusion (60 min.); (IR-PTX): PTX + ischemia (30min.) + reperfusion (60 min.); (IPC-IR-SS): 5 min. of ischemia + 5 minutes of reperfusion (IPC) + saline + ischemia (30 min.) + reperfusion (60 min.); (IPC-IR-PTX ): 5 min. of ischemia + 5 min. of reperfusion (IPC) + PTX + 30 min. of I + 60 minutes of R. Results: The IR-PTX, IPC-IR-SS and IPC-IR-PTX groups had significantly lower scores of mucosa damage than the IR-SS group. IR-PTX group showed higher scores than the IPC-IR-PTX group, in accordance with the hypothesis of a favorable effect of IPC alone or in association with PTX. Additionally, IPC-IR-SS had a higher damage score than the IPC-IR-PTX. The villi height and crypt depth were similar in all groups. The villi height in the IR-SS was significantly lower. Conclusion: Ischemic preconditioning or pentoxifylline alone protect the intestinal mucosa from ischemia/reperfusion injury. However, they do not have a synergistic effect when applied together.