Preventive effect of the flavonoid, quercetin, on hepatic cancer in rats via oxidant/antioxidant activity: molecular and histological evidences

BACKGROUND The incidence of hepatocellular carcinoma is increasing in many countries. The estimated number of new cases annually is over 500,000, and the yearly incidence comprises between 2.5 and 7% of patients with liver cirrhosis. The incidence varies between different geographic areas, being higher in developing areas; males are predominantly affected, with a 2:3 male/female ratio METHODS Experiments were designed to examine the effect of N-Nitrosodiethylamine (NDEA) as cancer-inducer compound and to confirm the preventive effect of the flavonoid quercetin on hepatocellular carcinoma in rats. Briefly, thirty six male albino rats of Wistar strain were divided into 3 groups: the 1st group was administered NDEA alone (NDEA-treated), the 2nd group was treated simultaneously with NDEA and quercetin (NDEA+Q) and the 3rd group was used as control (CON). Randomly amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) as well as p53-specifi PCR assays were employed to determine genomic difference between treated, and control animals. Histological confirmation as well as oxidant/antioxidant status of the liver tissue was done. RESULTS RAPD analysis of liver samples generated 8 monomorphic bands and 22 polymorphic bands in a total of 30-banded RAPD patterns. Cluster analysis and statistical analyses of RAPD data resulted in grouping control and NDEA+Q samples in the same group with 80% similarity cut-off value. NDEA-treated samples were clustered in a separate group. Specific PCR assay for polymorphism of P53 gene revealed a uniform pattern of allele separation in both control and NDEA+Q samples. Quercetin anticancer effect was exhibited in significant decrease of oxidative stress and significant decrease of antioxidant activity. Histopathological studies showed normal liver histology of the NDEA+Q samples. Meanwhile, several cancer-induced features were clearly observable in NDEA-treated samples. CONCLUSION This paper demonstrated that preventive effect of quercetin on hepatocarcinoma in rats by RAPD-PCR, tracing the effect on p53 gene and by histopathological evidence. Hereby, it was proved that quercetin exerted its preventive effect via decreased oxidative stress and decreased antioxidant activity.