الفهرس 
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Abstract
Liver toxicity is one of the most common causes of the liver disfunction and it may induce by different pollutants. The aim of the present study is to explore the hepatoprotective activity of steroidal saponins against CCl4 induced hepatotoxicity in albino rats. Twenty five rats were divided equally into 5 groups, five rats for each group. The first group, (G1), received basal diets and drinking water and served as untreated control. The other groups were received CCl4 (400mg CC14 /kg body weight) twice a week, the second group (G2) acts as positive control and the remaining three groups were daily administrated saponins for 6 weeks with concentration of 50, 100 and 200 mg/kg body weight in groups G3, G4, and G5 respectively. The hepatoprotective activity of steroidal saponins was evaluated by measurement of liver enzymes (i.e AST, ALT and ALP), Kidney function (i.e creatinine, urea), oxidative stress marker (MDA), cardic enzyme (i.e creatine kinase), and antioxidant defensive enzymes including catalase, glutathione peroxidase, glutathione reductase and superoxide dismutase in serum. The obtained results indicated that the treatment with CCl4 induced liver disfunction, renal disfunction, hyperlipedimea, hypercholesterolemia, reduction in HDL cholesterol, significant increase in LDL cholesterol and VLDL cholesterol. Also, the results clearly showed that the treatment with CCl4 reduced total protein, albumin, and globulin in serum. Moreover, the treatment with CCl4 resulted in remarkable increase in MDA and cardiac enzyme, creatine kinase, and significant reduction of the activities of catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase by 38.3%, 47.3%, 40.6% and 65.2% respectively.
Saponins treatment with concentration of 50, 100, and 200 mg/Kg body weight in G3, G4, and G5 rats respectively led to significant reduction in ALT, AST, and ALP in a concentration dependent matter. Also, saponin treatments improved renal function however, urea content and serum craetinine were redced and reached their level in untreated control after 6 weeks of treatment with saponins (G4 and G5). The lipid profile results indicated that saponin showed hypocholesterolemic, hypotriglyceridemic effects in CCl4 intoxicated rats. Moreover, Saponin treatments caused significant increase in HDL cholesterol and significant reduction in LDL cholesterol and VLDL cholesterol. In addition, the Cardiac enzyme, creatine kinase (CK), was significant reduced by saponin treatments by 23%, 37.2%, and 48.5% in G3, G4 and G5 respectively. Serum protein profile significantly increased by saponin treatment and reached the level of untreated control in case of G5 treatment. Regarding the antioxidant characteristics of steroidal saponins, saponins was found to cause significant reduction in lipid peroxidation (MDA). To reach the level of untreated control after 6 weeks of treatment with 200 mg saponins /kg (G5). Also the treatment G3 and G4 reduced the level of MDA in serum by 9.3% and 25.2% respectively. The reductive effect of different concentrations of saponins on lipid peroxidation is associated with significant activation of antioxidant enzymes including SOD, CAT, GSH-Px, and GSH-Rd. To clarify whether saponin activate the antioxidant enzymes through its ability to interact with the active site of the enzymes or not, in siclo molecular docking was performed between the active site of GSH-Px and saponin. The result of molecular docking illustrate that saponins has no hydrophilic or hydrophobic interactions with the amino acid residue of the catalytic site of glutathione peroxidase 4.
The present study concluded that steroidal saponin mitigates CCl4 induced hepatoxicity through its ability to activate the antioxidant defensive enzymes and prevent CCl4 induced oxidative damage. The activation of antioxidant enzymes could be due to their up-regulation and increase their syntheses in rat’s organs and tissues. Further investigation are needed to understand the mechanism by which steroidal saponins activate the antioxidant defense system.