“Involvement of reactive oxygen species (ROS) on the apoptotic mechanism induced by IFN-á2b in rat preneoplastic liver.”

ARIEL D. QUIROGA; MARÍA DE LUJÁN ALVAREZ; JUAN P. PARODY; MARÍA TERESA RONCO,; DANIEL E. FRANCÉS; GERARDO B. PISANI; CRISTINA E. CARNOVALE; MARÍA CRISTINA CARRILLO

BIOCHEMICAL PHARMACOLOGY

Elsevier

Año: 2007 vol. 73 p. 1776 - 1785

0006-2952

Interferon-a2b (IFN-a2b) is an important component in the preventive treatment of patients who have severe hepatic illness such as hepatitis B or C and hepatocarcinomas. In a previous work, using a rat liver preneoplastic model, we have demonstrated that IFN-a2b reduces the number and volume of altered hepatic foci (AHF) inducing apoptosis through a mechanism mediated by TGF-b1. In this study, the implication of hepatocytes redox status of IFN-a2btreated preneoplastic liver in the TGF-b1-induced apoptotic death was analyzed. Results indicate that IFN-a2b induces hepatocytic TGF-b1 production and secretion by induction of reactive oxygen species (ROS) formation through the activation of a membrane bound NADPH oxidase complex. TGF-b1, in turn, reduces hepatocytes antioxidant defenses and induces programmed cell death. On the other hand, it was also demonstrated that treatment of rats with IFN-a2b plus a ROS scavenger such as ascorbic acid, abolishes the apoptotic effect of IFN-a2b in rat preneoplastic livers, leading to an increase of the foci volume. In conclusion, these findings strongly suggest that ROS have a fundamental role as signaling and/or regulator molecules in the IFN-a2b-induced apoptosis in hepatic preneoplastic cells.a2b (IFN-a2b) is an important component in the preventive treatment of patients who have severe hepatic illness such as hepatitis B or C and hepatocarcinomas. In a previous work, using a rat liver preneoplastic model, we have demonstrated that IFN-a2b reduces the number and volume of altered hepatic foci (AHF) inducing apoptosis through a mechanism mediated by TGF-b1. In this study, the implication of hepatocytes redox status of IFN-a2btreated preneoplastic liver in the TGF-b1-induced apoptotic death was analyzed. Results indicate that IFN-a2b induces hepatocytic TGF-b1 production and secretion by induction of reactive oxygen species (ROS) formation through the activation of a membrane bound NADPH oxidase complex. TGF-b1, in turn, reduces hepatocytes antioxidant defenses and induces programmed cell death. On the other hand, it was also demonstrated that treatment of rats with IFN-a2b plus a ROS scavenger such as ascorbic acid, abolishes the apoptotic effect of IFN-a2b in rat preneoplastic livers, leading to an increase of the foci volume. In conclusion, these findings strongly suggest that ROS have a fundamental role as signaling and/or regulator molecules in the IFN-a2b-induced apoptosis in hepatic preneoplastic cells.a2b reduces the number and volume of altered hepatic foci (AHF) inducing apoptosis through a mechanism mediated by TGF-b1. In this study, the implication of hepatocytes redox status of IFN-a2btreated preneoplastic liver in the TGF-b1-induced apoptotic death was analyzed. Results indicate that IFN-a2b induces hepatocytic TGF-b1 production and secretion by induction of reactive oxygen species (ROS) formation through the activation of a membrane bound NADPH oxidase complex. TGF-b1, in turn, reduces hepatocytes antioxidant defenses and induces programmed cell death. On the other hand, it was also demonstrated that treatment of rats with IFN-a2b plus a ROS scavenger such as ascorbic acid, abolishes the apoptotic effect of IFN-a2b in rat preneoplastic livers, leading to an increase of the foci volume. In conclusion, these findings strongly suggest that ROS have a fundamental role as signaling and/or regulator molecules in the IFN-a2b-induced apoptosis in hepatic preneoplastic cells.b1. In this study, the implication of hepatocytes redox status of IFN-a2btreated preneoplastic liver in the TGF-b1-induced apoptotic death was analyzed. Results indicate that IFN-a2b induces hepatocytic TGF-b1 production and secretion by induction of reactive oxygen species (ROS) formation through the activation of a membrane bound NADPH oxidase complex. TGF-b1, in turn, reduces hepatocytes antioxidant defenses and induces programmed cell death. On the other hand, it was also demonstrated that treatment of rats with IFN-a2b plus a ROS scavenger such as ascorbic acid, abolishes the apoptotic effect of IFN-a2b in rat preneoplastic livers, leading to an increase of the foci volume. In conclusion, these findings strongly suggest that ROS have a fundamental role as signaling and/or regulator molecules in the IFN-a2b-induced apoptosis in hepatic preneoplastic cells.b1-induced apoptotic death was analyzed. Results indicate that IFN-a2b induces hepatocytic TGF-b1 production and secretion by induction of reactive oxygen species (ROS) formation through the activation of a membrane bound NADPH oxidase complex. TGF-b1, in turn, reduces hepatocytes antioxidant defenses and induces programmed cell death. On the other hand, it was also demonstrated that treatment of rats with IFN-a2b plus a ROS scavenger such as ascorbic acid, abolishes the apoptotic effect of IFN-a2b in rat preneoplastic livers, leading to an increase of the foci volume. In conclusion, these findings strongly suggest that ROS have a fundamental role as signaling and/or regulator molecules in the IFN-a2b-induced apoptosis in hepatic preneoplastic cells.a2b induces hepatocytic TGF-b1 production and secretion by induction of reactive oxygen species (ROS) formation through the activation of a membrane bound NADPH oxidase complex. TGF-b1, in turn, reduces hepatocytes antioxidant defenses and induces programmed cell death. On the other hand, it was also demonstrated that treatment of rats with IFN-a2b plus a ROS scavenger such as ascorbic acid, abolishes the apoptotic effect of IFN-a2b in rat preneoplastic livers, leading to an increase of the foci volume. In conclusion, these findings strongly suggest that ROS have a fundamental role as signaling and/or regulator molecules in the IFN-a2b-induced apoptosis in hepatic preneoplastic cells.b1, in turn, reduces hepatocytes antioxidant defenses and induces programmed cell death. On the other hand, it was also demonstrated that treatment of rats with IFN-a2b plus a ROS scavenger such as ascorbic acid, abolishes the apoptotic effect of IFN-a2b in rat preneoplastic livers, leading to an increase of the foci volume. In conclusion, these findings strongly suggest that ROS have a fundamental role as signaling and/or regulator molecules in the IFN-a2b-induced apoptosis in hepatic preneoplastic cells.a2b plus a ROS scavenger such as ascorbic acid, abolishes the apoptotic effect of IFN-a2b in rat preneoplastic livers, leading to an increase of the foci volume. In conclusion, these findings strongly suggest that ROS have a fundamental role as signaling and/or regulator molecules in the IFN-a2b-induced apoptosis in hepatic preneoplastic cells.a2b in rat preneoplastic livers, leading to an increase of the foci volume. In conclusion, these findings strongly suggest that ROS have a fundamental role as signaling and/or regulator molecules in the IFN-a2b-induced apoptosis in hepatic preneoplastic cells.a2b-induced apoptosis in hepatic preneoplastic cells. # 2007 Elsevier Inc. All rights reserved.2007 Elsevier Inc. All rights reserved.