The liver injury following ischemia and reperfusion is worse in experimental knockout heterozygote mouse model for expression of connexin 431.

Alexandre Maximiliano Trevisan,Thiago Pinheiro Arrais Aloiav,Bruno Cogliati,Jairo Marques Moreira,Adriana Ribeiro Homem,Nelson De Aquino Neto,Wellington Andraus,Leonardo Da Cruz Reno,Alexandre Moulin Naumann,Flavio Henrique Ferreira Galvão,Luiz Augusto Carneiro D'Albuquerque

doi:10.1590/s0102-865020190100000003

Alexandre Maximiliano Trevisan, Thiago Pinheiro Arrais Aloiav + Show 9 more

Open Access

https://doi.org/10.1590/s0102-865020190100000003

Copy DOI

Abstract

Purpose:To evaluate that Connexin (Cx43) plays a role in lesions after hepatic ischemia/reperfusion (IR) injury.Methods:We use Cx43 deficient model (heterozygotes mice) and compared to a wild group. The groups underwent 1 hour ischemia and 24 hours reperfusion. The heterozygote genotype was confirmed by PCR. We analyzed the hepatic enzymes (AST, ALT, GGT) and histology.Results:The mice with Cx43 deficiency showed an ALT mean value of 4166 vs. 307 in the control group (p<0.001); AST mean value of 7231 vs. 471 in the control group (p<0.001); GGT mean value of 9.4 vs. 1.7 in the control group (p=0.001); histology showed necrosis and inflammation in the knockout group.Conclusions:This research demonstrated that the deficiency of Cx43 worses the prognosis for liver injury. The topic is a promising target for therapeutics advancements in liver diseases and procedures.

Highlights

The number of liver surgeries such as transplantation and resection has increased exponentially over recent decades
When Aspartate transaminase (AST) was used to assess hepatic IR injury, a difference similar to that found with Alamine transaminase (ALT) was observed, with a p near zero (Fig. 6)
Animals lacking Cx43 have significantly larger risk of hepatic injury when submitted to this model of liver injury

Summary

Introduction

The number of liver surgeries such as transplantation and resection has increased exponentially over recent decades. It is important to control bleeding through the complete or partial impediment of blood flow to the liver[1]. This procedure leads to oxygen deprivation in the remaining tissue, causing tissue injury[2]. At the same time as minimizing bleeding during surgery, is known to induce hepatocellular stress. Patients are more able to withstand hepatic ischemia than the deleterious effects of large hemorrhages and subsequent blood transfusions and products[4]

Methods

Results

Conclusion