Polyol profile as an early diagnostic and prognostic marker in natural product chemoprevention of hepatocellular carcinoma in diabetic rats

Aim: Diabetes mellitus (DM) is a risk factor for hepatocellular carcinoma (HCC). It directs glucose to sorbitol and fructose in polyol pathway (PP). To pursue contribution of PP in hepatocarcinogenesis. Methods: We utilized ascorbic acid (AA) and diallyl sulfide (DAS) in experimental DM and HCC against control. HCC was induced by diethyl nitrosamine (DENA, one intraperitoneal (IP) dose 125 mg/kg), DM, by streptozotocin (STZ, IP dose 65 mg/kg). AA was given as 7.4 g/kg/d, I.P., DAS 200 mg/kg/d, orally. All animals were killed after 10 weeks. Results: DENA elevated serum AFP, erythrocyte sorbitol (ES), neoplastic changes in liver, lowered blood glucose, increased hepatocyte aldose reductase (AR) and sorbitol dehydrogenase (SDH), significantly alleviated by DAS/AA combination. DM elevated ES activating AR, inhibiting SDH, improved by DAS and AA. Conclusion: Co-induction of DM and HCC increased liver tissue lesion, serum AFP, ES, liver AR and SDH. Co-administration of DAS/AA reduced ES, AR without changing SDH. DAS/AA co-therapy lowered ES by depressing AR without affecting SDH, meaning that AR is activated by cancer and DM in different ways. PP is early marker for HCC detection and response to chemoprevention. DAS/AA combination is promising cost effective chemopreventive and anti-diabetic combination. Crown Copyright (C) 2011 Published by Elsevier Ireland Ltd. All rights reserved.