Asarone and metformin delays experimentally induced hepatocellular carcinoma in diabetic milieu

Abstract

Aims: The evidence suggests that the hyperglycemia and hyperinsulinemia of diabetes mellitus (DM) are risk factors for the development of hepatocellular carcinoma (HCC). The aim of the present study was to examine the effect of streptozotocin (STZ)-induced DM on promoting diethylnitrosamine (DEN) induced HCC in male wistar rats. Further, we investigated the administration of (α)-and (β)-asarone and metformin HCl on experimentally induced diabetic-hepatocellular carcinoma.

Materials and methods: Diabetes was induced by single dose of STZ (55 mg/2 ml/kg b.w. i.p.) and HCC by single dose of DEN (200 mg/ml/kg b.w. i.p.). Another group received the STZ followed by DEN two weeks later to mimic diabetic-HCC. The combined dose of (α)-and (β)-asarone (50 μg/1.5 ml/kg b.w. p.o. in the ratio of 1:1) and metformin HCl (250 mg/1.5 ml/kg b.w. p.o.) treatment was compared with the STZ + DEN group. The blood and liver samples were collected at the end of 12 and 18-weeks to study biochemical and histopathological changes in liver.

Key findings: The STZ induced diabetes promoted the tumor progression due to administration of DEN. The treatment of asarones and metformin significantly reduced the levels of glucose, glycosylated hemoglobin, liver dysfunction markers and tumor biomarkers along with an increase in level of insulin when compared to diabetic-HCC group. Histopathological examination indicated that asarones and metformin attenuate the inflammation, fibrosis, cirrhosis and development of spontaneous HCC.

Significance: The STZ can be used to promote the DEN induced HCC. Treatment with (α)-and (β)-asarone attenuates the effect of STZ + DEN induced HCC akin to metformin.

Keywords: (α)-and (β)-asarone; Diabetes mellitus (DM); Diethylnitrosamine (DEN); Hepatocellular carcinoma (HCC); Metformin HCl; Streptozotocin (STZ).