1H-NMR-based serum metabolomic study to evaluate the effect of asarone and metformin on experimentally induced diabetic hepatocellular carcinoma in rats

Abstract

BackgroundThe increased prevalence of hepatocellular carcinoma (HCC) in diabetic patients has focused on the need to characterize the role of altered metabolites in liver carcinogenesis. In this study, together with the serum biochemistry and histopathological observation, 1H nuclear magnetic resonance (1H-NMR)-based metabolomics was carried out to study the effect of asarone and metformin in diabetic HCC rats. Intraperitoneal administration of streptozotocin (STZ; 55 mg/kg b.w.) was used to induce diabetes in male Wistar rats. Further, 2 weeks later, after confirmation of diabetes, another group received diethylnitrosamine (DEN; 200 mg/kg b.w.) to simulate the diabetic HCC condition. The combined dose of α-and β-asarone (50 µg/kg b.w. in the ratio of 1:1) and metformin HCl (250 mg/kg b.w.) treatment was orally given to the diabetic HCC rats for 18 weeks. The serum samples were subjected to 1H-NMR-based metabolomics analysis to explore the metabolite changes at the end of the study.Results1H-NMR study quantitatively distinguished the metabolites, such as pyruvate, lactate, creatine, acetate, glutamine, valine, and alanine, which varied between the diabetic HCC and normal rats. Furthermore, compared to the diabetic HCC group, the administration of asarone and metformin resulted in a substantial change in metabolite levels. Histopathological examination indicated that treatment attenuates the magnitude of the toxic effect of STZ + DEN.ConclusionsThe aberrant glucose, lipid, and amino acid metabolisms were associated with developing hepatocarcinogenesis in rats during the diabetic condition. Treatment with asarone and metformin attenuated the metabolic changes due to STZ + DEN-induced diabetic HCC.