الفهرس 
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Abstract
The present study was designed to investigate whether zinc oxide nanoparticles has a possible protective and curative effect against DENA-induced HCC.
For the fulfillment of this concept, sixty male Swiss Albino rats were randomly divided into six groups, (n=10) as follows:
group 1: Rats didn’t receive any medication for 16 consecutive weeks and served as a control group.
group 2: Rats were administered DENA in their drinking water (100 mg/L) for 8 weeks and administered tap water for another 8 consecutive weeks.
group 3: Rats were injected of ZnONPs in a dose of (10 μg/kg) once weekly.
group 4: Rats were administered DENA orally daily for 8 consecutive weeks and ZnONPs (i.v.) in a dose of (10 μg/kg) once weekly for 4 weeks starting from a 13th week.
group 5: Rats were administered DENA orally daily for 8 consecutive weeks and ZnONPs (i.v.) in a dose of (10 μg/kg) once weekly for 16 weeks starting from first week.
group 6: Rats were administered DENA in their drinking water (100 mg/L) for 8 consecutive weeks with ZnONPs (i.p.) in a dose of (10 μg/kg) once weekly for 16 weeks starting from first week.
At the end of the experimental period, animals were lightly anesthetized using ether and retro-orbital plexus blood samples were collected and processed as in methodology in order to determine liver function parameters. Then the animals were euthanized by cervical dislocation and their livers were rapidly isolated for biochemical analysis and histopathological investigations. Biochemical analysis includes, tumor markers as [alpha fetoprotein (AFP) and alpha-L- fucosidase (AFU)] , liver function tests as, [serum Alanine aminotransferase (ALT), serum Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), serum - Glutamyltransferase (-GT), lactate dehydrogenase (LDH) and serum Total bilirubin (T.BIL)] and determination of liver contents of oxidative stress parameter as, [malondialdehyde (MDA), reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transverase (GST), catalase and as well as enzymatic activities of superoxide dismutase (SOD)]. Furthermore, apoptotic marker as caspase- 3 in liver tissue homogenate was also assessed.
Data in the present study showed that administration of DENA given in their drinking water (100 mg/L) for 8 weeks revealed significant increases in serum ALT (184.6%), AST (226%), ALP (352.3%), -GT (750%), LDH (228.7%) and T.BIL (640%). It also induced significant increases serum AFP (551%) and AFU (360.3%) as compared with the control group.
Moreover, DENA (100 mg/L) produced a significant increase in the content of caspase-3 (320%) and MDA (658%). It also induced significant decreases in GSH liver contents (6.16 %), GR (5.98 %), GST (15.44%), GPx (25.5 %) and the enzymatic antioxidant SOD & CAT activities (14.5% and 17.3%, respectively) in comparison with the control group. Furthermore, histopathological findings of liver tissue showed area of anaplastic hepatocyte, fibrosis degeneration in hepatocytes with multibiliary cysts.
The present study revealed that ZnONPs curative and protective effects against DENA-induced hepatocellular carcinoma (HCC) by abrogation of oxidative stress, apoptosis and tumor markers in rats. These effects were represented by significant reduction in the elevated serum levels of AFP and AFU with concomitant significant decrease in the serum liver enzyme activities in comparison with DENA-treated group. Further, they decreased the content of caspase-3 and MDA and increased GSH, GR, GST, GPx content as well as SOD & CAT activities in liver tissue, in comparison with DENA-treated group. In addition, treatment of rats with ZnONPs obviously mitigated the histopathological changes induced by DENA.
Based on the obtained results, the following conclusions could be drawn:
1) The results highlighted that DENA administration induced HCC. The toxicity was assessed by both biochemical and histological procedures.
2) ZnONPs could be ameliorated DENA-induced cellular apoptosis and oxidant / antioxidant in balance by decreasing liver cellular contents of caspase-3 and MDA and increasing their contents of GSH as well as activities of SOD & CAT enzymes with reduction in the elevated serum level of tumor markers (AFP and AFU) and extents of liver function parameters.
3) The obtained results may stimulate a future research work towards the possibility of using ZnONPs as an approach (as, a curative therapy and /or as, adjunctive therapy) for the abatement of experimental HCC.
4) The use of ZnONPs as alternative drug for treatment HCC should be considered. However, identification of more mechanistic pathways is needed for further exploring.