Romanian Society of Pharmaceutical Sciences

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THE ROLE OF MICRORNAS AS A DIAGNOSTIC BIOMARKERS IN THE EARLY PREDICTION OF ACETAMINOPHEN-INDUCED LIVER INJURY

DORA BOGHITOIU 1#*, ALINA GRAMA 2, TUDOR POP 2, ANCA SIMIONESCU 3, ISABEL
GHITA 4, CORIOLAN EMIL ULMEANU 1#, VIORELA NITESCU 1#

1Emergency Clinic Hospital for Children “Grigore Alexandrescu”, University of Medicine and Pharmacy “Carol Davila”,
Bucharest, Romania
22nd Paediatric Discipline, Department of Mother and Child, University of Medicine and Pharmacy “ Iuliu Hațieganu”, ClujNapoca, Romania
3Filantropia Hospital, University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
4Pharmacology and Pharmacotherapy Department, University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania

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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.