Circulating Mir-122 And Mir-192 As Specific And Sensitive Biomarkers For Drug-Induced Liver Injury With Acetaminophen In Rats

Background: Acetaminophen (APAP) poisoning is the most common drug intoxication, which often leads to acute liver failure and necrosis of liver tissue following the use of its excessive amounts.Objectives: In this study, the effects of toxic and therapeutic doses of acetaminophen were assessed on miR-122 and miR-192 compared to aminotransferase (AST and ALT) and liver pathological lesions in rats at the first and third hours of injection.Methods: In this study, 32 male Sprague-Dawley rats were randomly selected and divided into eight groups (four groups for the first-hour and four groups for the third-hour injection). In the case groups, three groups after one hour and three groups after three hours of injecting with APAP doses (75,150, and 300 mg/kg bw) intraperitoneally were sampled and killed. Changes in necropsy and macroscopic features of the rat liver were recorded after staining. The plasma levels of miR-122 and miR-192 were evaluated using the real-time PCR method and plasma levels of liver enzymes such as AST and ALT were measured by using an automated analyzer.Results: The histopathological examination at the dose of 150 mg/kg revealed mild hyperemia and edema in the portal areas, as well as mild infiltration of inflammatory cells. Centrilobular necrosis was mild at 300 mg/kg. ALT and AST activities were not significantly different between the case and control groups at the first hour, but they were significant between the groups receiving APAP for three hours. Moreover, the results of miRNA were significant at different times and doses (P < 0.05).Conclusions: Due to the ability to induce a protective system against acetaminophen toxicity, the plasma level of miR-122 and miR-192 activity at the early hours will be more helpful than measuring ALT and AST levels (P < 0.05).