الفهرس 
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Abstract
The present study was conducted to investigate the potential valorization of the environmentally polluting solid residue produced after olive oil extraction, olive pomace (OP), by solid state fermentation (SSF) using the safe yeast Kluyveromyces marxianus with assement of fermentation-enhanced qualitative and quantitative phenolic content, antioxidant activity, and chemo-preventive and chemotherapeutic rols against chemically induced hepatocellular carcinoma (HCC) in rats. Fermented OP (FOP) was developed by SSF of OP by K. marxianus. Both unfermented OP (UFOP) and FOP were extracted using methanol. Preliminary phytochemical screening of UFOP methanolic extract (UFOPME) and FOP methanolic extract (FOPME) indicated identical profiles. HPLC results confirmed alteration of phenolic profile of OP after fermentation with reinforcing its content of rutin, vanillin, cinnamic acid, quercetin, catechin and syringic acid. However, fermentation decreased OP gallic, caffeic and p-coumaric acids contents. FOPME showed higher antioxidant than UFOPME in ABTS radical scavenging, metal chelating, H2O2 scavenging, lipid peroxidation inhibition activities, reducing power and total antioxidant capacity. On the other hand, UFOPME showed slightly higher superoxide anion radical scavenging and RBCs protecting activities than FOPME. The anticancer activity of UFOPME and FOPME was assessed in vivo against diethylnitrosamine (DENA)-induced HCC in rats. A total of 80 adult male albino Wistar rats were randomly divided into 8 groups: normal control group, HCC group, UF control group, F control group, pre-UF group, pre-F group, post-UF group, and post-F group. The experiment extended for 16 weeks. Biochemical analyses results indicated that compared to normal group, administration of DENA/CCl4 in HCC group resulted in hepatic and nephro-toxicity (indicated by a significant increase in serum liver enzymes activities and kidney function markers), oxidative stress (indicated by a significant increase in NO and MDA, and a significant decrease in total antioxidant concentration in liver homogenate), in addition to significant increases in serum level of AFP, and liver concentrations of CYP450, uPA, VEGF, MMP-2, MMP-9, and Bcl-2. UF and F control groups showed non-significant differences compared to normal group in all examined biochemical parameters indicating the safety of both extracts for in vivo application. Biochemical analyses results indicated that both UFOPME and FOPME can protect against and relieve DENA/CCl4-induced HCC in rats acting as anti-angiogenic, anti-metastatic, and pro-apoptotic agents with relieving the oxidative stress. UFOPME and FOPME (at the studied concentration) are the same in their effect since both can restore normal levels of different biomarkers as indicated by insignificant difference between pre-UF and pre-F groups as well as between post-UF and post-F groups. However, UFOPME may be better than FOPME in targeting uPA and FOPME is better than UFOPME in targeting angiogenesis. Improvement in biochemical parameters agreed with liver macroscopic and histological examinations.