الفهرس 
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Abstract
Liver fibrosis is the progressive accumulation of connective tissue in the liver, which can be caused by chronic liver injury of various etiologies.
Moringa oleifera, or the horseradish tree, is a pan-tropical species that is known by such regional names as benzolive, drumstick tree, marango it belongs to the species of Moringaceae family. Its leaves are rich of macro- and micronutrients, including polyphenols, phenolic acids, vitamins, carotenoids, flavonoids, and alkaloids. Therefore, Moringa oleifera plant is used in nurturing both animal and human as an excellent nutritive supplement. It has also, used as antioxdant, anticancer, anti-inflammatory, hepato-protective and antifungal activities. On the other hand, previous studies showed that ethanolic extract of Moringa oleifera leaves can effectively protect hepatic tissue from tissue damage induced by thioacetamide.
Colchicine is a plant alkaloid. It is effective against gouty arthritis and other forms of rheumatic diseases (rheumatoid arthritis, familial Mediterranean fever, Bechet´s disease, etc). Colchicine inhibits the migration of granulocytes into the inflamed area and inhibits the metabolic and phagocytic activity of granulocytes. Further, colchicine is anti-mitotic and anti-fibrotic. Colchicine retards the microtubule-mediated transport of pro-collagen and enhances collagenase activity. Colchicine decreased liver fibrosis in rats with TAA induced liver fibrosis.
Our study thrown light on the hepatoproticitve effect of moringa olifera ethanolic extract and colchicine on thioacetamide induced liver fibrosis in rats through determination of the following parameters:
8. Liver function tests (serum ALT, AST, ALP, GGT, BILIRUBIN).
9. Serum proteins ( total protein, Albumin, Globulin, Alb/glob ratio)
10. Serum lipid profiles.
11. Molecular genes (BAX, Bcl2).
12. Antioxidant capacity ( total antioxidant, MDA,GSH)
13. Liver weight, bodyweight.
14. Histopathological examination of the liver.
Preparation of Moringa oleifera ethanolic leaves extract
(MOEL)—Leaf extract was prepared according to amethods previously described by Nilanjan et al.; 2012 with some modifications. Leaves of Moringa oleifera were purchased from Alexandria Farmers Association for Rural Development. Leaves were thoroughly washed in distilled water and dried in a vacuum oven at 50 °C for 10 h. Clean, dry leaves were crushed and 5 g of the powder was mixed with 50 mL of 90% ethanol. The mixture was stood in a container for approximatly 24h and filtered afterward. The resulting filtrate was evaporated in a rotary evaporator to remove alcohol (adjustment bath: 40-45 °C, rotation: 50 rpm, pressure: ” ” ” " ~ " ” ” ”15 psi, condenser: 4 °C) to avoid denaturation of the active ingredients. The alcohol residue of sample was weighted (” ” ” " ~ " ” ” ”500 mg) and dissolved in 100 mL distilled water to constitute the final extract solution (5 mg/mL).
Determination of Yield of Extract
The percentage yield of the extract was determined by weighting the coarse Moringa oleifera leaf before extraction and the Moringa oleifera ethanol leaf extract after concentration and then calculated using the formula.
Percentage(%) yield = Weight (g) of the concentrated X100
Weight (g) of the ground Moringa leaves
This study was carried out on a total number of 105 male albino rats weighting 150± 20 g and about 90 ± 10 days old were collocated into seven groups (15 rats per each group). The experiment lasted for two months, through which all groups except for control and control positive were given moringa olifera ethanolic leaves extract (MOLE) and colchicine (col). Liver fibrosis was induced by intraperotineal injection of thioacetamde (150 mg/kg) in groups II, V, VI VII while other groups were injcted with 0.9% normal saline of the same volume as flow:
group I: Control group : kept on basal ration and water ad libitum
group II: Thioacetamide (TAA) (control +ve) group: kept on basal ration and liver fibrosis was induced via intraperotineal injection of thioacetamide dissolved in 0.9 NaCl solution a dose of 150 mg/kg body weight three times a week for 8 weeks.
group III: colchicine (COL) 50µg/kg that given by stomach tube in a dose of (50 μ/kg day) was dissolved in 0.9 normal salin for 8 weeks+ kept on basal ration .
group IV: moringa olifera ethanolic leaves extract (MOEL) 400mg/kg. That given by stomach tube.
group V: Thioacetamide (TAA)150 mg/kg + colchicine (COL) 50µg/kg (TAA +Col).
group VI: Thioacetamide (TAA) 150 mg/kg +moringa olifera ethanolic leaves extract (MOLE) 400mg/kg (TAA + MOLE)
group VII: Thioacetamide (TAA) 150mg/kg +moringa olifera ethanolic leaves extract (MOLE) 400mg/kg+ colchicine (COL) 50µg/kg (TAA +COL+ MOLE).
The same previous dose by the same route + TAA injection (at the same previous dose by the same route for the same period). Body weight was measured three times a week to detect the dose for each rat.
This study concluded that:
1- The administration of TAA leading significant increase in serum liver enzyme level ALT, AST, ALP, GGT, Bilirubin as compared to control group, while treatment with COL, MOLE causing significant decreased serum liver enzyme level by (P<0.05) than induced hepatic group. In general there are no a fundamental difference between groups V, VI, VII
2- Also revealed that, the injection of thioacetamide (TAA) 150mg/kg induced liver fibrosis characterized by drastic decrease in total protein and albumin and non-significant to globulin as compared to control group by (p <0.05). The COL or MOEL was able to restore dysfunction by increased globulin, albumin and significant increase in total protein as compared to liver induced fibrosis group. While their combination only increased globulin than hepatic group.
3- Injection of thioacetamide induced liver fibrosis characterized by drastic decrease in serum levels of triacylglycrol (TG) and vLDL , also illustrated that (TAA) significantly increased total cholesterol and LDL while HDL still unchanged as compared to control group. That due to TAA alters fatty acid composition in tissues, thus decline fatty acid biosynthesis in the liver and lowering serum T-triglyceride. On the other hand oral administration with colchicine and moringa olifera ethanolic leaves extract improvement significantly liver function that due to their ability to suppress levels of inflammatory mediators and prevent cholesterol crystal–induced neutrophil-mediated inflammation implicated in liver fibrosis.
4- The demonstrated data also revealed that, the injection of thioacetamide induced liver fibrosis characterized by drastic decrease in total anti-oxidant capacity (TAC) and reduced glutathione (GSH) with significant increase in malondehyde (MDA) as compared to control group.
5- Treatment of hepatic rats with COL or MOEL and their combination leading to significant restores to oxidative stress results as compared to injected thioacetamide only group.
6- Moreover the induction of liver fibrosis and apoptosis by thioacetamide were detected by significant increase in BAX pro-apoptotic gene expiration and significant decrease in Bacl2 anti apoptotic gen expiration. Our study showed that when rats given COL or MOEL or their combination that resulted that significant increase in Bacl2- and significant decrease in BAX which lead to improvement in liver function and in general improvement in immunohistochmesrty of the liver.
7- Liver weight was significantly increased in thioacetamide group and body weight was significantly decreased as compared to control group these effects were revealed by administration of COL and MOEL.
In general the treatment with colchicine and moringa olifera showed good restore in chemical, molecular and histopathological function of liver. Also we detected that there are no differences between them.