Study on the mechanism of cantharidin‐induced hepatotoxicity in rat using serum and liver metabolomics combined with conventional pathology methods. Issue 9 (28th May 2020)

• Record Type: Journal Article
• Authors: Zhang, Jianyong; Chen, Qihong; Wang, Le; Chen, Kuan; Mu, Wenbi; Duan, Cancan; Li, Xiaofei
• Is Part Of: Journal of applied toxicology. Volume 40:Issue 9(2020)
• Page Start: 1259
• Page End: 1271
• Publication Date: 2020-05-28
• Subjects: Cantharidin -- conventional evaluation -- hepatotoxicity -- metabolomics -- rats model; Toxicology -- Periodicals; Industrial toxicology -- Periodicals; Environmentally induced diseases -- Periodicals; Toxicology -- Periodicals; 615.9005
• DOI: 10.1002/jat.3983
• Languages: English
• ISSNs: 0260-437X

Abstract

Abstract: Cantharidin (CTD), a compound secreted from Mylabris species, exhibits strong antitumor properties; however, hepatotoxicity restricts its clinical application. The mechanism by which CTD induces toxicity remains unclear. In the present study, the hepatotoxicity of CTD in the rat was investigated using a metabolomic approach combined with conventional pathology methods. A total of 30 rats were intragastrically treated with two doses of CTD (0.75 and 1.5 mg/kg) for 15 days to evaluate hepatotoxicity. Serum and liver samples were collected for biochemical dynamics analyses, histopathological examination and metabolomic analysis. It was found that liver index and serum biochemical indices were significantly increased. Furthermore, the pathology results showed that hepatocytes and subcellular organelles were damaged. Metabolomics analysis found 4 biomarkers in serum and 15 in the liver that were associated with CTD‐induced hepatotoxicity. In addition, these were responsible for CTD hepatotoxicity by glycerophospholipid metabolism, sphingolipid metabolism, and steroid hormone biosynthesis. In conclusion, conventional pathology and metabolomics for exploring hepatotoxicity can provide useful information about the safety and potential risks of CTD. Abstract : Metabolomics combined with conventional methods were used to explore cantharidin (CTD)‐induced hepatotoxicity in rat. Using serum and liver metabolomics, 4 biomarkers in the serum and 15 in the liver were found to be associated with CTD hepatotoxicity. The hepatotoxicity of CTD appears to involve three metabolic pathways: glycerophospholipid metabolism, sphingolipid metabolism, and steroid biosynthesis.