Analysis of the effect of Tamoxifen on the liver function of Wistar rats subjected to the experimental model of hepatic ischemia and reperfusion

• Grant number: 24/23477-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2025
• End date: January 31, 2026
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Filipe Miranda de Oliveira Silva
• Grantee: Tainá Soares Leite Santos
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

INTRODUCTION: In liver transplantation, up to 10% of early liver failures are caused by ischemia and reperfusion (IR) injury, with a higher incidence of acute and chronic rejection, thus increasing the need for re-transplantation. Oxidative stress as well as the inflammatory process are important mechanisms of cell injury. In this context, drugs with anti-inflammatory, anti-fibrotic and anti-proliferative effects, such as Tamoxifen, may represent an interesting strategy. In other experimental models, it has been demonstrated that Tamoxifen acts by blocking Th1 cytokines. Apparently, most of the effects of this drug are due to the modulation of estrogen receptors. Therefore, experimental models that aim to understand the mechanisms involved in IR, such as the experimental model of hepatic IR, are extremely important. OBJECTIVE: The objective of the present study is to analyze the effects of tamoxifen on liver function in animals subjected to the experimental model of hepatic ischemia and reperfusion. METHODS: Twenty-four male Wistar rats will be studied and divided into three groups: SHAM group (n=8) - without IR; IR group - rats subjected to hepatic ischemia and reperfusion (1 hour of ischemia and 4 hours of reperfusion) (n=8); Tamoxifen group - animals pretreated with tamoxifen and subjected to the IR process. The animals will be subjected to partial hepatic ischemia (70%) for a period of 1 hour and a reperfusion period of 4 hours. The drug will be administered by gavage at a dose of 10mg/kg in two doses: 24 hours before and 2 hours before hepatic IR, considering the pharmacokinetics of the drug in which it reaches its maximum plasma concentration after 2 hours of oral administration and has an average half-life of 24 hours. Serum levels of the following biochemical markers will be evaluated: AST, ALT, Gamma GT, Serum Albumin and Alkaline Phosphatase.