Investigation of metabolite alteration in dimethylnitrosamine-induced liver fibrosis by GC–MS

Abstract

Background: A metabolomic study of biomarkers associated with dimethylnitrosamine (DMN)-induced hepatic fibrosis in Sprague-Dawley rats was performed using GC–MS. The clinical chemistry of the collected blood and the histopathology of excised liver samples were examined, and urine samples were prepared by solvent extraction. Results: Through pattern analysis, the DMN-treated group was divided into two subgroups based on the aspartate aminotransferase (AST) levels compared with the control, a moderately higher group (DMN subgroup A) and a significantly higher group (DMN subgroup B). Uric acid, orotic acid, N-phenylacetylglycine and glutaric acid were biomarkers for DMN subgroup A, aminomalonic acid was a biomarker for DMN subgroup B, and arabitol level distinguished control versus DMN treatment regardless of AST level. Conclusion: This study suggests that the identification and profiling of AST level-related metabolites may be useful as a diagnostic tool and for the study of the mechanism of liver fibrosis induced by DMN.