EFFECT OF STREPTOZOTOCIN-INDUCED HYPERGLYCEMIA ON THE PROGRESSION OF HEPATOCARCINOGENESIS IN RATS

Abstract

Diabetes mellitus and hepatocellular carcinoma both have detrimental impact on health worldwide. Type II diabetes and liver cancer share many causative fact ors, but biological correlation between the two dis eases still remains elusive. The study was aimed to evalu ate the effect of induction of diabetes during the development of hepatocarcinogenesis in rats. Rats w ere divided into four groups namely, normal control , diabetic control, carcinogen control and carcinogen treated rats treated with streptozotocin (to make them diabetic). Hepatocarcinogenesis was initiated in ra ts by diethylnitrosamine (200 mg kg -1 body weight, single i.p. injection on day 0 only). Then 2-acetyl aminoflourene (0.5% w/w) was given daily in diet fo r 18 weeks to promote the carcinogenesis. On the 16th week, streptozotocin (65 mg kg -1 body weight, single i.p. injection) was administered to initiate diabetes in rats. On the 20th week, animals were sacrificed an d various biochemical changes and histopathological a lterations in liver were investigated. Carcinogen t reated rats made diabetic had significantly lower cytochro me P-450 content as compared to diabetic control ra ts and had slightly elevated cytochrome P-450 level as compared to that of carcinogen control rats. Marke d enhancements of UDP-glucuronosyl transferase, glutathione S-transferase activities and lipid peroxidat ion levels were observed in carcinogen treated rats mad e diabetic as compared to those activities and leve ls in diabetic control and carcinogen control rats. Histo pathological investigation of hepatic tissue has fa voured the rapid progress of development of hepatocellular carcinoma in carcinogen treated rats made diabetic . In conclusion, induction of diabetes during the develo pment of hepatocellular carcinogenesis inevitably promotes the progression of the later disease.