Effects of creatine supplementation in schemia-reperfusion injury after lung transplantation in rats

• Grant number: 13/20010-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2013
• End date: November 30, 2014
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Rogerio Pazetti
• Grantee: Katiusa de Abreu Alves
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Ischemia-reperfusion (IR) is a complication that can raise the risk of death after lung transplantation, by activating the innate immune system to induce inflammation. This occurs when the supplemental oxygen in the lungs is stopped (ischemia) followed by reperfusion period. During ischemia, oxygen supply is below metabolic needs, resulting in depletion of cellular reserves of ATP and increased production of reactive oxygen species (ROS) and nitrogen (RNS). ROS and ERNs are able to react and modify the molecular structures of lipids, carbohydrates, proteins and deoxyribonucleic acid, leading to structural and functional damage of the cells. Additionally, the IR also triggers an intense inflammatory process, characterized mainly by the presence of neutrophils and macrophages, which release numerous inflammatory mediators, perpetuating inflammation. The lock of each of these steps is an attempt to mitigate the injury, thereby preventing dysfunction of the organs involved in IR, especially the lungs.This knowledge has evolved along with the study of antioxidants capable of neutralizing the effects of ROS and RNS. Accordingly, supplementation with creatine (Cr) has been studied, and its benefits in cases of cerebral IR are assigned by favoring the increased levels of phosphocreatine (PCr), which facilitates the formation of adenosine triphosphate (ATP) cell, promoting the maintenance of intracellular Ca2 + levels and discourage formation of ROS and therefore the inflammatory process. Therefore, in this study we aimed to verify whether creatine supplementation has beneficial effects against IR injury in a model of lung transplantation in rats.