Abstract
MicroRNA-122 (miRNA-122), also known as liver-specific miRNA, has recently been shown to be a potent biomarker in response to liver injury in mammals. The objective of this study was to examine its expression in response to toxicant treatment and acute liver damage, using the zebrafish system as an alternative model organism. For the hepatotoxicity assay, larval zebrafish were arrayed in 24-well plates. Adult zebrafish were also tested and arrayed in 200 mL cages. Animals were exposed to liver toxicants (tamoxifen or acetaminophen) at various doses, and miRNA-122 expression levels were analyzed using qRT-PCR in dissected liver, brain, heart, and intestine, separately. Our results showed no significant changes in miRNA-122 expression level in tamoxifen-treated larvae; however, miRNA-122 expression was highly induced in tamoxifen-treated adults in a tissue-specific manner. In addition, we observed a histological change in adult liver (0.5 μM) and cell death in larval liver (5 μM) at different doses of tamoxifen. These results indicated that miRNA-122 may be utilized as a liver-specific biomarker for acute liver toxicity in zebrafish.
Highlights
During the process of drug development, many compounds fail somewhere along the pipeline due to drug-induced toxicity
We investigated the expression of miRNA-122 during the initiation and progression of acute liver injury induced by liver toxicants
In our previous report [20], severe cell death in zebrafish was visualized as a reduction of transparency following metronidazole treatment
Summary
During the process of drug development, many compounds fail somewhere along the pipeline due to drug-induced toxicity. Half of these compounds are removed due to hepatotoxicity, including necrosis, steatosis, cholestasis, proliferation, inflammation, and bile duct hyperplasia [1]. Drug-induced liver injury (DILI) has been established as a major cause of acute liver failure in the United States. Rapid and accurate detection of hepatotoxicity remains a vital issue in new drug development. Various model systems have been developed to enable detection of potential liver toxicity of chemicals and drugs [4]. In comparison to rodents and nonhuman primates, there are numerous advantages to the use of zebrafish as a toxicological model species
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