الفهرس 
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Abstract
Today, Food additives play important role to meet the requirements of growing population during production and presentation of plentiful, tasty and nutritious food Synthetic color is added to foods to replace natural color lost during production or processing. It causes health problems specifically: Carcinogenicity leading to cancer development, genotoxicity leading to mutations or damaging chromosomes in bacteria, fungi, insects and mammalian cells in vivo and in vitro and neurotoxicity leading to the damage of nerve tissue. Some studies indicated that medicinal plants play vital roles in reduced hazardous of using synthetic coloring and flavor.
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.
one hundred and sixty healthy rats, weighing 130-190 g were divided into 20 groups. (1) Control group; in which animals were received distilled water (2)
C . citratus group; in which animals were received C . citratus methanolic extract 200mg / kg . (3) S.offcinalis group; in which animals were received S.offcinalis ethanolic extract 200mg / kg.(4) C. citratus + S.offcinalis group (MIX); in which animals treated with half concentration of both C .citratus and S.offcinalis extracts .(5) stra ; in which animals treated with synthetic flavor strawberry 3% .(6) Stra+c; in which animals treated with synthetic flavor of strawberry3% and C. citratus extracts 200mg / kg.(7) Stra+ s; in which animals treated with synthetic flavor of strawberry 3% and S.offcinalis extracts200mg / kg (8) Stra+ mix; in which animals treated with synthetic flavor strawberry 3% and mixture extracts (9)Mango; in which animals treated with synthetic flavor of mango 3%.(10) Mango+ s; in which animals treated with synthetic flavor of mango3%and S.offcinalis extract 200mg / kg (11) Mango+ c; in which animals treated with synthetic flavor mango3%and C. citratus extract 200 mg / kg (12) Mango+ m; in which animals treated with synthetic flavor of mango 3%and mixture extract (13)Allura; in which animals treated with synthetic colorant allura red 400mg/kg diet (14) Allura+ c; in which animals treated with synthetic colorant allura red400mg/kg diet and C.citratus extracts200 mg / kg.(15) Allura+ s; in which animals treated with synthetic colorant allura red400mg/kg diet and S.offcinalis extracts 200 mg / kg (16) Allura+ Mix; in which animals treated with synthetic colorant allura red 400mg/kg diet and mixture extract (17) Brilliant; in which animals treated with synthetic colorant Brilliant blue 400mg/kg diet (18) Brilliant+ c; in which animals treated with synthetic colorant brilliant blue 400mg/kg diet and C.citratus extract 200 mg / kg (19) Brilliant+ s; in which animals treated with synthetic colorant brilliant blue400mg/kg diet and S.offcinalis extract 200 mg / kg (20) Brilliant + mix; in which animals treated with synthetic colorant brilliant blue400mg/kg diet and mixture extract. The experimental lasted two months.
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, ALP total and direct bilirubin, total protein and albumin), kidney function (urea and creatinine and uric acid), and lipid profile (TC, TG, HDL-c and LDL-c).
• Hematological investigation as RBC, WBC, HB, MCV, MCH and MCHC
• Histopathological changes in liver, kidney, lung, brain and heart .
Body weight
Body weight gain was significantly decreased in group treated with synthetic flavor of strawberry and mango in addition to allura red and brilliant blue by about 31.3% ,26.9% respectively compared to the control group. Pretreated groups with C.citratus and S.officinalis extracts and their mixture reduced body weight gain compared to group treated with strawberry, mango, allura and brilliant blue, but not return to control.
Feed efficiency ratio was decreased in group treated with strawberry, mango, allura and brilliant blue by about 27.08%,20.8%,33.3% and 23.9% respectively comparing with normal control. pretreated group with C.citratus and S.officinalis extracts and their mixture showed slight improve in the feed efficiency ratio compared with groups treated with synthetic flavor strawberry, mango, synthetic coloring allura red and brilliant blue.
Changes in relative weight of some organs
There were no significant differences among groups in all relative weight organs except the liver in group treated with brilliant blue which was decreased significantly (P < 0.05) by about 35.2%comparing with control .While brain weight in group treated with brilliant blue decreased significantly (P < 0.05) by about 31.8% comparing with control.
Hematological parameters
Hemoglobin level in groups treated with synthetic flavor strawberry, mango, synthetic coloring allura red and brilliant blue were decreased about 22%, 26.9 % , 23% and 27.7% ,respectively comparing to normal control. Whereas, the treatment with C.citratus and S.officinalis extracts and their mixture plus synthetic flavorings or colorants restored hemoglobin level to nearly normal control. In addition, the treatment with strawberry, mango flavors , allura red and brilliant blue caused a reduction in red blood cell count by about 12.5%, 18.7%, 18.7% and 24.4% respectively comparing with normal control. Whereas, the treatment with C. citratus and S.officinalis extracts or their mixture extracts plus synthetic flavorings or colorants restored hemoglobin level to nearly normal control.White blood cell count was significantly (P < 0.05) increased in the groups treated with strawberry, mango flavors, allura and brilliant blue by about 1.8,1.7,1.3 and 1.6fold compared to normal control. While the treatment with C.citratus, S.officinalis and their mixture extract plus strawberry decreased WBCs by about 13.2%,20.6% and 13.3% respectively compared to group treated with strawberry alone. In addition, the presence of S.officinalis, C. citratus and their mixture extract plus mango decreased WBCs by about 17.3%,13.7%,and38% respectively comparing with group treated with mango alone.whereas groups treated with C. citratus, S.officinalis and their mixture extract plus allura decreased WBCs about 9.6%.23.8% and14.7% respectively comparing with group treated with allura alone .on the other hand, concomitant treatment with C.citratus and S.officinalis extracts and their mixture plus brilliant blue decreased WBCs about 28.6%,27.1%and 29.6% respectively comparing with group treated with brilliant blue alone.
Liver function
The serum AST ,ALT and ALP activity increased in groups treated with allura red and brilliant blue .Whereas groups treated with strawberry ,mango, allura red and brilliant blue plus C. citratus extract, S. Officinalis extract, mixture extracts decreased AST ,ALT and ALP activity compared with group treated with strawberry ,mango, allura red or brilliant blue alone .
Bilirubin
The treatement with strawberry ,mango flavors , allura red and brilliant blue increased significantly the serum TB1.4,3.7,2.9 and 2.1 fold and DB 2.3,3.9,4.8 and 2.6 respectively comparing with control. Whereas the treatement with strawberry ,mango, allura red or brilliant blue plus C. citratus , S. Officinalis , mixture extracts decreased TB and DB comparing with groups treated with strawberry ,mango, allura red or brilliant blue alone .
Kidney function
The serum urea levels were significantly increased about 8.3,7.9,8.8 and 8.3 fold in group treated with strawberry ,mango, allura red and brilliant blue.whereas creatinine was increased by about 2.7,2.7,2.7 and 2.6 fold.while uric acid levels were increased by about 4.1,3.8,3.3and 3.3 fold compared with the control group. However, the serum levels of the urea, uric acid and creatinine revealed a significant decrease in a treatment with C. citratus , S.Officinalis or their mixture extract .
Total Protein and Albumin
Treated with synthetic strawberry ,mango, allura red and brilliant blue increased significantly the serum protien, albumin and globulin comparing with control . However, the serum levels of the protien, albumin and globulin revealed a significant decrease in a treatment with C. citratus , S. Officinalis or their mixture extract.
Lipid profile parameters
Treated with synthetic strawberry ,mango, allura red and brilliant blue increased significantly in the serum TC, TG and LDL-c comparing with control .while treated with strawberry ,mango, allura red and brilliant blue plus C. citratus extracts, S. Officinalis extracts, mixture extracts decreased TC, TG and LDL-c comparing with group treated with synthetic strawberry ,mango, allura red and brilliant blue alone.