Pathophysiological Changes During Ischemia-reperfusion Injury in Rodent Hepatic Steatosis

Abstract

Background/Aim: Ischemia and reperfusion injuries may produce deleterious effects on hepatic tissue after liver surgery and transplantation. The impact of ischemia-reperfusion injury (ΙRΙ) on the liver depends on its substrate, the percentage of liver ischemic tissue subjected to IRI and the ischemia time. The consequences of IRI are more evident in pathologic liver substrates, such as steatotic livers. This review is the result of an extended bibliographic PubMed search focused on the last 20 years. It highlights basic differences encountered during IRI in lean and steatotic livers based on studies using rodent experimental models. Conclusion: The main difference in cell death between lean and steatotic livers is the prevalence of apoptosis in the former and necrosis in the latter. There are also major changes in the effect of intracellular mediators, such as TNFα and IL-1β. Further experimental studies are needed in order to increase current knowledge of IRI effects and relevant mechanisms in both lean and steatotic livers, so that new preventive and therapeutic strategies maybe developed.

The Immunological Basis of Liver Allograft Rejection

“…Steatotic livers are being increasingly utilized for transplantation. Steatosis is associated with increased PRI as measured by molecular markers of inflammation ( 14 ) and reflected histologically as increased hepatocyte necrosis ( 15 ). Clinically, the sequelae of PRI in DCD livers include an increased risk of primary non-function and ischemic-type biliary lesions and overall reduced graft survival ( 16 ).…”

Ischemia/Reperfusion Injury of Fatty Liver Is Protected by A2AR and Exacerbated by A1R Stimulation through Opposite Effects on ASK1 Activation

“…In recent decades, several methods, mostly targeting singular IR-induced alterations, were found to be able to reduce the IRI in both lean and fatty livers in animal models [2,4]. Among them, ischemic preconditioning (IP), which is induced by a short interruption of blood flow followed by re-perfusion [30], emerged due to its powerful and multifaced beneficial effects [18,19,31,32].…”

“…Several pathogenic mechanisms might contribute to the increased hepatic IRI that is induced by fatty infiltration [4]. Among them, the upregulation of the mitochondrial uncoupling protein-2 with the increased production of oxidative species (OS) [5], the induction of endoplasmic reticulum stress (ERS) and the activation of inflammatory reactions play critical roles [6].…”

d-Pinitol protects against endoplasmic reticulum stress and apoptosis in hepatic ischemia-reperfusion injury via modulation of AFT4-CHOP/GRP78 and caspase-3 signaling pathways

“…Hepatic IRI is a major clinical problem associated with patients who undergo liver surgery, transplantation, and circulatory shock. 28 , 29 Studies demonstrate that IRI-induced insult, which stimulates the generation of ROS, the release of inflammatory cytokines, microvascular modification, and induction of apoptosis, results in hepatocellular dysfunction. 29 , 30 Furthermore, treatment options are very limited for the clinical management of hepatic IRI.…”

“… 28 , 29 Studies demonstrate that IRI-induced insult, which stimulates the generation of ROS, the release of inflammatory cytokines, microvascular modification, and induction of apoptosis, results in hepatocellular dysfunction. 29 , 30 Furthermore, treatment options are very limited for the clinical management of hepatic IRI. Thus, many researchers have investigated the antiapoptotic potential of various therapeutic moieties for the treatment of hepatic IRI.…”