الفهرس 
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Abstract
Human hepatocellular carcinoma is the fifth most commonly occurring cancer in the world and the third greatest cause of cancer mortality. In fact, 54% of hepatocellular carcinomas develop in China, where the major risk factors are hepatitis B infection and ingestion of foodstuffs contaminated with aflatoxins .
Plant material have been known to be used in the management of degenerative diseases (such as mental illness, microbial infection, cancer) so many people in developing countries depend on herbal medicine.
The experiments were carried out in Agricultural Chemistry Department, Faculty of Agriculture, Minia University. The animals were housed in plastic cages. The rats were kept under normal healthy laboratory conditions. Sixteen male wistar rats (Rattus norvegicus) weighting. The rats were randomly divided into ten experimental groups. 180-240 g were divided in to ten groups.
group (1) : served as the control group, orally received H2O/day.
group (2): rats were administrated orally daily with M. oleifera leaves ethanolic extract (250 mg/kg b.wt orally) for 9 weeks.
group (3): rats were administreated orally daily with ethanolic M. oleifera leaves ethanolic extract (500 mg/kg b.wt orally) for 9 weeks.
group (4): rats were administrated orally daily with methanolic S. officinalis leaves ethanolic extract (100 mg/kg b.wt orally) for 9 weeks.
group (5): rats were administrated orally daily with methanolic S. officinalis leaves extract (200 mg/kg b.wt orally) for 9 weeks.
group (6): rats were injected with AFB1 (0.4 µg / kg B.W i.p. once ), then after 30 min injected with CCl4 (1 ml/kg b. wt,1:1 mixture with paraffin oil i.p. Madkour et al., 2012), twice per week for 6 weeks to induce liver fibrosis.
group 7, 8 rats were administrated orally daily with M. oleifera leaves ethanolic extract (250 and 500 mg/kg b.wt orally) for 3 weeks before, injected with AFB1 (0.4 µg / kg B.W i.p. once ) and 6 weeks concurrently with CCl4. group 9, 10 rats were administrated orally daily with S. officinalis leaves methanolic extract (100 and 200 mg/kg b.wt orally) for 3 weeks before, injected with AFB1 (0.4 µg / kg B.W i.p. once ) and 6 weeks concurrently with CCl4.
Body weight was recorded weekly during the experimental period (9 weeks) and daily food intake was determined. Feed efficiency was calculated daily during the adaptation and the experimental pediods.
The following parameters were studied:
• Body growth including: average daily weight gain, organs weight and daily food efficiency.
• Some blood parameters including liver function (AST, ALT, total and direct bilirubin, total portion and albumin), kidney function (urea and creatinine), and lipid profile (total cholesterol, TG, HDL-c and LDL-c).
• Hematological investigation as RBC, WBC, HB, HCT, MCV, MCH, MCHC and differential leukocyte count.
• The liver tissues were homogenated and hepatic (MDA, CAT and GSH) were determined.
• Histopathological changes in liver, kidney, lung, spleen, brain, heart and testis.
Results.
1. Effect of M. oleifera , S. officinalis extracts and with AFB1 + CCl4 on changes body weight of rats:
The body weight gain was significantly decreased in the AFB1 + CCl4 intoxicated group about 45% compared with control group. Meanwhile, pretreated groups with ethanolic M. oleifera and S. officinalis extracts lowered significantly the reduction of body weight gain about 7% and 17% respectively in the low dose and 38% and 36% respectively in the high dose compared to intoxicated group (AFB1+CCl4). However, ethanolic M. oleifera and methanolic S. officinalis extracts alone at two doses significantly increased the body weight gain compared to control group.
Feed efficiency Ratio was increased in rats administrated with ethanolic M. oleifera and methanolic S. officinalis extracts alone but not significant whereas it was decreased in rats injected with AFB1 + CCl4 (i.p.). On the other hand, pretreated group with high dose ethanolic M. oleifera and methanolic S. officinalis extracts improved the feed efficiency Ratio.
2. Changes in organs weight index:
The weight of the liver, kidney and spleen in the intoxicated group significantly increased about 84, 28 and 51% respectively, comparing with control group. While, pretreated groups with M. oleifera and methanolic S. officinalis extracts at two doses, the weight of the liver was significantly decrease whereas, high dose more effective to returned the spleen weight to control. The lung, heart, testis and brain weights were not significantly different compared with control.
3. Hematological Determinations:
The hematological studies of the animals administrated with the ethanolic M. oleifera and methanolic S. officinalis leaves extracts alone at two doses for 9 weeks showed no significant differences in the Hb, PCV, WBCs and RBCs levels when compared with control. Intoxicated AFB1 + CCl4 rats, Hb, PCV and RBCs were significantly decreased compared to control group about 29, 12 and 26% respectively, while WBCs was increased about 48.6 % relative to normal control.
On the other hand, pretreated groups with M. oleifera and methanolic S. officinalis extract caused significant increased in blood Hb, PCV and RBCs level. Meanwhile, WBCs was decreased significantly comparing with the mean value of intoxicated group.
4. Liver biomarkers of rats:
ALT, AST and ALP levels were used as biochemical markers for evaluation of hepatic injury. A significant elevation in serum AST, ALT and ALP levels about 1.7, 2.1 and 1.6 fold respectively was observed in AFB1 + CCl4 -treated rats compared with control group. However, the serum levels of these biomarkers revealed significant decrease in pretreated rats with ethanolic M. oleifera extracts and methanolic S. officinalis extracts comparing with AFB1+ CCl4 -treated group. Nevertheless, treatment with ethanolic M. oleifera and methanolic S. officinalis extracts alone did not show any significant changes in all markers when compared to control group.
Also, the data of serum total and direct bilirubin levels revealed no significant changes in groups treated with ethanolic M. oleifera and methanolic S. officinalis extract alone compared with control group. While a significant increase in total and direct bilirubin levels in rats injected with AFB1 + CCl4 about 100 and 115 % respectively when comparing with normal control group. While, significantly decreased were recorded for groups treated with two doses ethanolic M. oleifera and methanolic S. officinalis extract before administration of AFB1+ CCl4 about 19, 38, 15 and 29 % respectively for total bilirubin and 14, 22, 7 and 10 % respectively for direct bilirubin compared to intoxicated rats.
5. Total Protein, Albumin:
Treatment with ethanolic M. oleifera and methanolic S. officinalis extracts alone revealed no significant changes in total protein, albumin levels relative to control group. While, intoxicated rats with AFB1+ CCl4 induced significant decreased in total protein, albumin and globulin levels about 30, 33 and 28 % respectively, compared with normal control.
While, pre-treated groups with both doses of ethanolic M. oleifera and methanolic S. officinalis extracts caused significantly elevated in total protein, albumin and globulin compared with AFB1 + CCl4 group.
6. Urea and Creatinine:
AFB1 + CCl4 groups showed significant increase in serum urea and creatinine levels about 1.4 fold compared with control group. Meanwhile, pretreated groups with ethanolic M. oleifera and methanolic S. officinalis extracts reduced the elevation of serum urea and creatinine compared with intoxicated group (AFB1+CCl4).
Whereas two doses of ethanolic M. oleifera and methanolic S. officinalis extracts alone have no effect on renal function markers compared to control.
7. Estimation of lipid profile:
Treated rats with ethanolic M. oleifera and methanolic S. officinalis leaves extract alone appeared no significant changes in TC, TG, HDL, LDL and VLDL levels compared with control group. Rats treated with AFB1+CCl4, the levels of TC, TG, LDL and VLDL were significantly increased about 35, 42, 222 and 42% respectively, while, significant decreased in HDL level about 26% compared with control group. The pretreated groups with ethanolic M. oleifera and methanolic S. officinalis appeared significant decreased in TC (11, 17, 7 and 13 % respectively), TG (8, 19, 5 and 14 %), LDL (31, 42, 21 and 35 %) and VLDL (8, 19, 5 and 14 %). While, HDL was a significantly increased about 13, 18, 11 and 17 % respectively comparing with AFB1+CCl4-intoxicated group.
8. Oxidative enzymes:
AFB1+CCl4 significantly increased lipid peroxides level about 44% and significantly decreased CAT, GSH levels about 49 and 39 % respectively, as compared with control group. Whereas, pretreatment of rats with either low dose of ethanol M. oleifera and methanol S. officinalis extract or high dose afforded significant protection against AFB1 + CCl4 -intoxication and maintained level of lipid peroxides at near basal level with significant increase in GSH level when compared with AFB1 + CCl4 treated group. Furthermore, animal’s treated with ethanol M. oleifera and methanol S. officinalis extract alone did not show any significant alterations in oxidative stress markers as compared to the control group.
9. Histological examination
Histological changes were screened to support the tested biochemical markers of organs injury. The histopathological results showed that M. oleifera and S. officinalis alone was found to be safe and did not induce any histopathological changes in all organs. While, pretreated groups with M. oleifera and S. officinalis leave extract was partially prevented and markedly reduced as a protective or therapeutic agent.