Effect of creatine on liver normothermic ischemia and reperfusion injury in rats

• Grant number: 17/20759-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2018
• End date: May 31, 2019
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Fernando Silva Ramalho
• Grantee: Diego Forti
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Liver injury secondary to ischemia and reperfusion (I/R) occurs in clinical situations in which there is a temporary and complete interruption of blood flow in the hepatic pedicle, as in severe hepatic trauma, major hepatectomies and liver transplantation. In the pathogenesis of this lesion there is the participation of acute inflammatory response, microcirculatory deficit and hepatic oxidative stress resulting from the generation of reactive oxygen and nitrogen species by phagocytic cells. Creatine is an important source of energy for hepatocellular metabolism, in addition to exhibiting anti-inflammatory and antioxidant properties. The present study aims to evaluate the effect of oral supplementation with creatine on liver injury following normothermic I/R in rats. Male Wistar rats will be submitted to oral treatment with saline (control) or creatine (0.25, 0.5 or 1.0 g/kg of body weight/day) for 5 consecutive days, followed by the surgical procedure for induction of hepatic normothermic ischemia for 60 minutes. The animals will then undergo euthanasia six hours after hepatic reperfusion. The degree of hepatocellular damage (serum level of aminotransferases and histological score of tissue damage), hepatic oxidative stress intensity (malondialdehyde concentrations), hepatic levels of transcription factor NRF2 and reduced glutathione (GSH), and intensity of liver acute inflammatory response (hepatic neutrophil accumulation, activation of the transcription factor NFºB, and gene expression of cytokines IL-1beta and TNF-alpha).