The Role of Micrornas as a Diagnostic Biomarkers in the Early Prediction of Acetaminophen-Induced Liver Injury

Abstract

Toxic liver injury can vary from asymptomatic increases in biochemical parameters (hepatic function tests) to acute hepatitis and acute liver failure or death. Because this parameters changes only after the hepatocellular necrosis and changes are not proportional to the extension of the hepatic injuries, we need new biological markers to facilitate an early diagnosis, allowing a rapid and targeted therapeutical intervention. Our study aimed to analyse the changes in serum levels of some miRNAs after acetaminophen exposure in mice and their correlation with the severity of liver histopathological lesions. The serum level of miRNA-122 and miRNA-192 and the histopathological aspects were assessed at 30 minutes, 2 hours, and 24 hours after intraperitoneal administration of acetaminophen. Thirty minutes post-exposure, there were no significant differences regarding the necrosis score between the acetaminophen and control groups, but the miRNA-122 values varied significantly. The level of miRNA-122 had the highest increase after 2 hours, long before any change in the serum level of the usual markers. Regarding the expression miRNA-192, at 30 minutes post-exposure, there was an increase compared to the controls, but with a magnitude inferior to that recorded for miRNA-122 (0.62 vs. 2.1). Also, after 2 and 24 hours, the increase was much less significant than for miRNA-122. With a high specificity for hepatocytes and increased stability, the serum level of miRNA-122 is modified during the early stages, even before the histopathologic changes. All of these are the necessary attributes to be a biomarker of toxic hepatic injury. miRNA-192 cannot be considered a sensitive and specific enough biomarker to toxic liver injury. RezumatBoala hepatică toxică variază de la creșteri asimptomatice ale parametrilor biochimici (teste funcționale hepatice) la hepatită acută, insuficiență hepatică acută sau deces. Deoarece acești parametri se modifică numai după necroza hepatocelulară și modificările nu sunt proporționale cu extinderea leziunilor hepatice, avem nevoie de noi markeri pentru un diagnostic precoce și o intervenție terapeutică rapidă și țintită. Studiul nostru a analizat modificările nivelurilor serice ale unor microARN (miARN) după expunerea la acetaminofen la șoareci și corelația acestora cu severitatea leziunilor histopatologice hepatice. Modificările miARN-122 și 192 și aspectele histopatologice au fost evaluate la 30 de minute, 2 ore și 24 de ore după administrarea intraperitoneală de acetaminofen. La treizeci de minute după expunere, nu au existat diferențe semnificative ale scorului de necroză între lotul expus și martor, dar valorile miARN-122 au variat semnificativ. Nivelul miARN-122 a avut cea mai mare creștere după 2 ore, cu mult înainte de orice modificare a markerilor obișnuiți. În ceea ce privește miARN-192, la 30 de minute după expunere, a existat o creștere comparativ cu lotul martor, dar cu o magnitudine inferioară celei înregistrate pentru miARN-122 (0,62 față de 2,1). De asemenea, după 2 și 24 de ore, creș...

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