Background: Toosendan Fructus is traditionally used as an insecticide or digestive tract parasiticide for treating digestive parasites in China. It is recorded to have little toxicity in Chinese Pharmacopoeia and has been found to cause severe liver injury during clinical practice. Purpose: This study aims to identify candidate serum microRNAs (miRNAs) as potential toxicological biomarkers for reflecting the hepatotoxicity induced by toosendanin (TSN), which is the main toxic compound isolated from Toosendan Fructus
Methods: Alanine/aspartate aminotransferase (ALT/AST) activities detection and liver histological observation were performed to evaluate the liver injury induced by TSN or other hepatotoxicants in mice. miRNAs chip analysis and Real-time PCR assay were conducted to identify the altered miRNAs in serum from TSN-treated mice
Results: The results of serum ALT/AST and liver histological evaluation showed that TSN (10 mg/kg) induced hepatotoxicity in mice. The results of miRNAs chip showed that the expression of 81 serum miRNAs was obviously altered in mice treated with TSN for 12 h, and 22 of them have passed the further validation in serum from mice treated with TSN for both 6 h and 12 h. These 22 miRNAs were supposed to be the candidate toxicological biomarkers for TSN-induced hepatotoxicity with more sensitivity as compared to the alteration of AST or ALT activity. Moreover, the expression of miRNA-122-3p and mcmv-miRNA-m01-4-3p was not only increased in TSN-treated mice, but also increased in mice treated with other hepatotoxicants including acetaminophen (APAP), monocrotaline (MCT) and diosbuibin B (DB). Only the expression of serum miRNA-367-3p was increased in TSN-treated mice but not changed in the liver injury induced by APAP, MCT or DB
Conclusion: miR-122-3p and mcmv-miRNA-m01-4-3p may be two commonly sensitive biomarkers for reflecting the hepatotoxicity induced by exogenous hepatotoxicants, and miR-367-3p may be a specific biomarker for reflecting the liver injury induced by TSN.
[1]Shanghai Univ Tradit Chinese Med, Inst Chinese Mat Med, MOE Key Lab Standardizat Chinese Med, Shanghai Key Lab Compound Chinese Med, Shanghai 201203, Peoples R China.
[2]Shanghai Univ Tradit Chinese Med, Inst Chinese Mat Med, SATCM Key Lab New Resources & Qual Evaluat Chines, Shanghai 201203, Peoples R China.
[3]Shanghai Univ Tradit Chinese Med, Innovat Res Inst Tradit Chinese Med, Ctr Drug Safety Evaluat & Res, 1200 Cailun Rd, Shanghai 201203, Peoples R China.
[4]Nanjing Univ Med Sch, Affiliated Hosp, Nanjing Drum Tower Hosp, Nanjing 210008, Jiangsu, Peoples R China.
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