Influence of pentoxifylline in cellular and biochemical changes in rats exposed to tobacco smoke

• Grant number: 12/00104-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): April 01, 2012
• Effective date (End): March 31, 2013
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Paula Schmidt Azevedo Gaiolla
• Grantee: Fernando Rodrigues da Camara Oliveira
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Smoking is considered one of the most important risk factors that affect the heart. Among the possible mechanisms that participate in cardiac remodeling induced by cigarette smoke are increased oxidative stress, inflammation, and apoptosis. Pentoxifylline (PTX) is a phosphodiesterase inhibitor with immunomodulatory properties. Evidence indicates that the modulation of inflammation is a mechanism by which PTX may attenuate cardiac remodeling. However, these mechanisms may not be likely related to the inhibition of TNF-±. The beneficial effects of PTX in the heart through inhibition of TNF-± are controversial. On the other hand, inhibition of apoptosis by PTX seems to be an important mechanism in the attenuation of cardiac remodeling. In addition, PTX has an antioxidant role by inhibiting, for example, superoxide dismutase and heme oxygenase. Therefore, it is possible that inflammation (assessed by methods other than the cytokine), apoptosis, and oxidative stress participate in cardiac abnormalities induced by tobacco smoke exposure. Moreover, these alterations may be reduced by pentoxifylline. The objectives of this study are to evaluate the participation of a) inflammation by quantification of the inflammatory infiltrate in the heart, b) analysis of apoptosis by caspase-3, c) and oxidative stress in the hearts of rats previously exposed to tobacco smoke. To this end, we will study the serum and storage tissues of 32 animals that were previously allocated to four groups of animals: nonsmoking controls (C) and smokers (EFC / C), and animals treated with pentoxifylline, non-smokers (PTX), and smokers (EFC / PTX). Smoking is considered one of the most important risk factors that affect the heart. Among the possible mechanisms that participate in cardiac remodeling induced by cigarette smoke are increased oxidative stress, inflammation, and apoptosis. Pentoxifylline (PTX) is a phosphodiesterase inhibitor with immunomodulatory properties. Evidence indicates that the modulation of inflammation is a mechanism by which PTX may attenuate cardiac remodeling. However, these mechanisms may not be likely related to the inhibition of TNF-±. The beneficial effects of PTX in the heart through inhibition of TNF-± are controversial. On the other hand, inhibition of apoptosis by PTX seems to be an important mechanism in the attenuation of cardiac remodeling. In addition, PTX has an antioxidant role by inhibiting, for example, superoxide dismutase and heme oxygenase. Therefore, it is possible that inflammation (assessed by methods other than the cytokine), apoptosis, and oxidative stress participate in cardiac abnormalities induced by tobacco smoke exposure. Moreover, these alterations may be reduced by pentoxifylline. The objectives of this study are to evaluate the participation of a) inflammation by quantification of the inflammatory infiltrate in the heart, b) analysis of apoptosis by caspase-3, c) and oxidative stress in the hearts of rats previously exposed to tobacco smoke. To this end, we will study the serum and storage tissues of 32 animals that were previously allocated to four groups of animals: nonsmoking controls (C) and smokers (EFC / C), and animals treated with pentoxifylline, non-smokers (PTX) and smokers (EFC / PTX).(AU)