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

<p>Abstract</p> <p>Background</p> <p>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</p> <p>Methods</p> <p>Experiments were designed to examine the effect of <it>N</it>-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 1^stgroup was administered NDEA alone (NDEA-treated), the 2^ndgroup was treated simultaneously with NDEA and quercetin (NDEA+Q) and the 3^rdgroup was used as control (CON). Randomly amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) as well as <it>p53</it>-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.</p> <p>Results</p> <p>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 <it>P</it>⁵³gene 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.</p> <p>Conclusion</p> <p>This paper demonstrated that preventive effect of quercetin on hepatocarcinoma in rats by RAPD-PCR, tracing the effect on <it>p53 </it>gene and by histopathological evidence. Hereby, it was proved that quercetin exerted its preventive effect via decreased oxidative stress and decreased antioxidant activity.</p