Therapeutic Role of Quercetin against Experimentally Induced Hepatocellular Carcinoma in Female Albino Rats and their offspring

Abstract

Aim: To evaluate the potential role of quercetin against N-methyl nitrosourea (MNU)-induced hepatocellular carcinoma (HCC) in pregnant rats and their offspring. Material & Methods: Twenty-four female rats were used in this study. Six rats were preserved without treatment and the other eighteen female rats were induced by a single dose of MNU (50 mg /kg B wt). After confirmation of the positive tumor marker test, female rats were placed with the males for mating. The pregnant rats were divided into four groups (n=6). Group1: control rats, group2: Quercetin supplemented rats (20 mg/kg B.Wt, group3: MNU-induced rats, and group4: MNUtreated rats followed by supplementation with quercetin. At the end of the weaning period, the mothers and their offspring (at 21 days old postnatal) of all groups were sacrificed, the liver was removed immediately for histological and immunohistochemical investigations. Also, blood samples were collected, centrifuged, and processed for the estimation of antioxidants. Results: In the control and quercetin groups, the histological investigation of the liver of mother rats and their offspring appeared with normal architecture. In Group3 (MNU-induced group) the liver sections of mother's rats revealed degenerated hepatic lobules with pronounced cellular hyperplasia (HCC) especially around the central vein and portal area as well as numerous Kupffer cells and fat droplets. However, the liver sections of offspring displayed little cellular hyperplasia but the central and portal veins appeared damaged and congested with blood. Immunohistochemically, the liver sections of MNU-induced mother's rats and their offspring appeared strongly stained with α-FP antibody and negatively stained with caspase-3 antibody. Furthermore, the levels of serum antioxidants; SOD, CAT&GSH were significantly decreased however the levels of MDA and NO were significantly increased in MNU-induced mother rats and their offspring if compared with control. In group 4, quercetin was able to restore the histological and immunohistochemical changes in the liver induced by MNU. Also, the levels of antioxidants, as well as MDA and NO, were markedly restored near to the normal level as in control. Conclusion: Quercetin has a powerful therapeutic role against MNU-induced HCC in pregnant rats and their offspring.