الفهرس 
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Abstract
Liver is the largest internal organ (the skin being the largest organ overall) and the largest gland in the human body. It is located in the right upper quadrant of the abdominal cavity, resting just below the diaphragm. The liver lies to the right of the stomach and overlies the gallbladder.
It is connected to two large blood vessels, one called the hepatic artery and the other portal vein. The hepatic artery carries blood from the aorta, whereas the portal vein carries blood containing digested nutrients from the entire gastrointestinal tract and also from the spleen and pancreas. These blood vessels subdivide into capillaries, which then lead to a lobule. Each lobule is made up of millions of hepatic cells which are the basic metabolic cells. Lobules are the functional units of the liver.
Liver is responsible for the mainstay of protein metabolism, synthesis as well as degradation. It is also responsible for a large part of amino acid synthesis. The liver plays a role in the production of clotting factors as well as red blood cell production. Some of the proteins synthesized by the liver include coagulation factors I (fibrinogen), II (prothrombin), V, VII, VIII, IX, X and XI, as well as protein C, protein S and antithrombin. In the first trimester fetus, the liver is the main site of red blood cell production. By the 32nd week of gestation, the bone marrow has almost completely taken over that task. The liver is a major site of production for thrombopoietin, a glycoprotein hormone that regulates the production of platelets by the bone marrow. Liver plays a major role in carbohydrate, protein, amino acid, and lipid metabolism. Liver performs several roles in carbohydrate metabolism.
The liver synthesizes and stores approximately 100g of glycogen via glycogenesis, the formation of glycogen from glucose. When needed, the liver releases glucose into the blood by performing glycogenolysis, the breakdown of glycogen into glucose. The liver is also responsible for gluconeogenesis, which is the synthesis of glucose from certain amino acids, lactate or glycerol. Adipose and liver cells produce glycerol by breakdown of fat, which the liver uses for gluconeogenesis.
Parsley (Petroselinum crispum Mill.) is cultivated throughout the world and used as a spice, salad and herbal remedy. Use of parsley in food has a long history going back to ancients, Greeks and Romans. It has been reported to have possible medicinal attributes as an antioxidative, antimicrobial, anticoagulant, antihyperlipidemic and antihepatotoxic.
Parsley uses includes treatment of nose bleeding, hematoma, skin blemishes due to it’s bleaching properties, halitosis, ear ache, otitis, and as an emenagogue favouring menstruation and alleviating it’s pains. The myristicin and apiole contained in the plant have the properties to increase the production of oestrogen which make their use relevant in menopause. However, large amount can have uterotonic effect and therefore it’s use is contraindicated in pregnancy and ingestion of more than 10 drops a day of the oil may cause abortion. Parsley is also widely used as a galactofuge by lactating mothers to stop excessive milk production.
Although, the use of the plant is discouraged in heart and kidney disorders due to its water retention capabilities, however, its anti inflammatory and probable immune boosting properties make it relevant in the traditional treatment of urinary tract infection, nephritis, cystitis and prevention of renal stones formation. In addition, it is also a common home remedy for obesity and reduction of itching in insect bites.
So our study aimed to investigate the effect of parsley (fresh and dried) at three levels ( 5, 10 and 20%) compare with drug on hepatotoxic rats.
Materials and Methods:
Parsley was put on cotton mattress on table to get rid of out moisture for one day. Then cut parsley into small pieces and put on the table under fan in a dark room for 7 days. Finally parsley exposure to the sun light for a day and grinding. Eighty Male Albino rats (n = 80) of Sprague Dawley strain weighing (150±10g) were housed in well aerated individual wire cages under hygienic laboratory (Ophthalmology Institute in Giza).
Experimental Design:-
After five days, rats were divided into two main groups as follows:-
•First main group negative control (-ve) group (8 rats) was fed on basal diet during the period.
•Second main group (72rats) were injected subcutaneously a single dose of CCL4 was dissolved in paraffin oil (1:1) in dose 1ml / kg body weight for three days from the start of the experimental period for inducing rats liver injuries, after that, 8 rats were sacrificed to insure of injury according to the method.
Rats which injected by CCL4 were classified as following:
•First main group negative control (-ve) group (8 rats) was fed on basal diet during the period.
•Second main group (72rats) were injected subcutaneously a single dose of CCL4 was dissolved in paraffin oil (1:1) in dose 1ml / kg body weight for three days from the start of the experimental period for
inducing liver injuries, after that, 8 rats were sacrificed to insure of injury according to the method described by lee et al ., (2005).
Rats which injected by CCL4 were classified as following:
•The first subgroup was left as a positive control (+ve) fed on basal diet only.
•The second subgroup fed on basal diet and administrated orally with dissolved drug in distilled water in adose 10 mg ∕ kg of rat intragastric .
•The third subgroup fed on basal diet contained fresh parsley at level 5%.
•The fourth subgroup fed on basal diet contained fresh parsley 10%.
•The fifth subgroup fed on basal diet contained fresh parsley at level 20%.
•The sixth subgroup fed on basal diet contained dried parsley at level 5%.
•The seventh subgroup fed on basal diet contained dried parsley at level 10%.
•The eighth subgroup fed on basal diet contained dried parsley at level 20%.
Food intake (FI), body weight gain (BWG), feed efficiency ratio (FER)and organs weight as a percent of total body weight were determined according to body weight gain was determined using the following equations:
Feed intake = Initial weight diet (gm) – Loss weight diet (gm)
Relative weight of organs = Organs weight/ Final body weight× 100
Body Weight Gain% = × 100
Initial weight (gm)
Final weight (gm) – initial weight (gm)
Feed Efficiency Ratio = Gain in body weight (g)/Feed intake(g).
Biochemical analysis:
Each sample was placed in a dry clean centrifuge tube, then centrifuged for 10 minutes at 3000 r.b.m /min to separate the serum. Serum was carefully separated into dry clean Ebendorf tubes by using Pasteur pipette and kept frozen till analysis.
Determination of liver function Serum (ALT , AST, ALK, Bilirubin) activity, Determination of kidney functions(HDL-c, VLDL-c, LDL-c, A/G) , Lipid profiles (Total Protien, Albumin, Globulin and Atherogenicindex and (T.colestrol, Triglycerides)
Histopathologicalexaminations:
The kidneys of sacrificed rats were taken and immersed in 10% formalin solution. The fixed specimens were then trimmed, washed and dehydrated in ascending grades of alcohol. They were then cleared in xylol, embedded in paraffin, sectioned at 4-6 microns thickness and stained with Heamtoxylin and Eosin.
Statistical analysis
Results and Discussion:
1- Body weight gain , FER and Food intake,
Results showed that there were no significant differences (P<0.05) between negative control with other all groups in body weight gain. Values of mean±SD for FER were 8.01 ±5.38, 6.53±3.10, 6.45±4.38 6.71±2.61, 7.94±3.60, 6.68±3.19, 6.68 ±2.32, 7.32±2.37and 6.70±3.78 (g/ day) for negative and positive control ,drug and fresh and dried parsley at three levels ( 5, 10 and 20 %) respectively. The above results showed that, there were no significant differences (P ≤0.05) between
negative control with other all groups. Concerning food intake results found that, Drug group was the lowest value while fresh parsley at level 5% was the highest value in food intake. On the other hand, results showed that, there were significant differences(P≤0.05) between fresh parsley at level 5% , negative and positive control and dried parsley at level 5% and other all groups. While, there were no significant differences (P<0.05) between all groups except fresh parsley at level 5% and drug group.
2-Relative weight of Organs:
Our results showed that there were decreased significant differences (P≤0.05) between negative control VS. fresh parsley at level 10% and drug group. On the other hand there were no significant differences (p<0. 05) between positive control with other all groups under study in relative weight of kidney. The results of relative weight for liver showed that, there were no significant differences (P<0.05) between negative control with other all groups. Values of mean±SD were 3.33 ±0.97, 2.92±0.47, 2.87±0.67 , 2.92±0.31, 2.87±0.46 , 2.85±0.47 , 3.07 ±0.57 , 3.18±0.47 and 3.15±0.63 g for negative and positive control , drug group and fresh and dried parsley at three levels (5,10 and 20 %) respectively.
3-Kidney and Liver Functions:
Our results found that, there were decreased significant differences (p≤0. 05) between positive control with other all groups except fresh parsley at level 20%. On the other hand, there were no significant differences (p<0.05) between negative control ,fresh parsley at two levels (5and 10 % ) dried parsley at levels (5,10 and 20%) and drug group for serum total protein Concerning serum Albumin results showed that, there were decreased significant differences (p≤0. 05) between positive control
VS. drug group. While, there were no significant differences (p<0. 05) between negative control with other all groups under study.
Moreover, our results showed that, there were decreased significant differences (p≤0.05) between positive control Vs negative control, fresh parsley at two levels (5and10%) and dried parsley at level 5%. Besides that, there were no significant differences (p<0. 05) between dried parsley at two levels (10 and 20 %) and drug group with other all groups under study. Concerning of serum urea The above results showed that, there were decreased significant differences (p≤0. 05) between positive control with other all groups. Also, there were no significant differences (p<0. 05) between negative control, fresh parsley at two levels 5, 10 % and drug group . Also, between fresh parsley at level 20% and dried parsley at three levels (5, 10 and 20%).
oncerning of G ratio results dried parsley at level 5% is the highest group while, positive control is the lowest one there were decreased significant differences (P ≤0.05) between dried parsley at level 5% with other all groups. Values of mean ±SD were 1.50 ±0.98, 1.06±0.37, 0.89±0.60, 2.07±1.78, 1.91±1.57, 3.87 ±3.08, 1.86±0.91 and 1.42±0.51 mg/dl for negative and positive control, drug group and fresh and dried parsley at three levels (5, 10 and 20 %) respectively.
4- Liver Enzymes
Results of liver functions showed the effect of type of parsley (fresh and dried) at different levels (5, 10 and 20%) on liver functions (ALP, ALT, AST and Bilirubin). Results for serum ALP showed that, there were decreased significant differences (p≤0.05) between control positive and fresh parsley at level 5% VS. negative control, drug group and fresh and dried parsley at level 20%. On the hand, there were no
significant differences (p 0.05) between all groups except positive control and fresh parsley at level 5%. Values of mean ±SD were 128.70±5.39, 150.13±8.05, 120.97±8.29 ,143.67±15.66, 131.60±4.72, 120.16±13.19, 130.33±19.03, 130.61±6.14and 125.70±3.89 mg/dl for negative and positive control, drug group and fresh and dried parsley at three levels (5, 10 and 20 %) respectively.
Results of serum ALT showed that, there were decreased significant differences (p≤0.05) between positive control VS. negative control, fresh parsley at two levels (5and 10 %), dried parsley at two levels (5 and 20 % )and drug group. Besides that, there were no significant differences (p<0.05) between fresh parsley at level 20% and dried parsley at level 10% with other all groups.
Results of serum AST showed that, there were decreased significant differences (p≤0.05) between positive control VS. negative control, fresh parsley at three levels (5, 10 and 20 %) and dried parsley at level 5%. On the other hand, there were no significant differences (p<0.05) between fresh parsley at three levels (5, 10 and 20%) , dried 5% and negative control. Also, between dried parsley at level 20% with all groups under study except negative control and fresh parsley at level 10%.
Results for serum Bilirubin showed that, there were decreased significant differences (p≤0.05) between positive control and dried parsley at level 20% with other all groups. Values of mean±SD were 0.71±0.04, 1.25±0.26, 0.78±0.07, 0.69±0.13, 0.77±0.15, 0.83±0.09, 0.87±0.09, 0.84±0.09 and 1.27±0.44mg/dlfor negative and positive control, drug group and fresh and dried parsley at three levels (5, 10 and 20%) respectively.
5- Lipid Profiles:
Our results showed the effect of type (fresh and dried) of parsley at different levels (5,10 and 20%) on Lipid profile (HDL-c ,LDL-c VLDL-c and Atherogenic index). Results for serum HDL-c showed that, there were increased significant differences (P≤0.05) between positive control with other all groups. On the other hand, there were no significant differences (p<0.05) between negative control, drug group and fresh and dried parsley at level 5% . Also, between fresh and dried parsley at two levels (10 and 20%). Also, between dried parsley level 5% with other all groups. The values of mean±SD were 60.90±5.02, 41.40±6.59, 61.25±8.53, 59.85±6.82,52.20±6.42,50.43±7.72, 53.16±5.92, 51.25±4.91 and 49.06±5.40 mg/dl for negative and positive control, drug group and fresh and dried parsley at three levels (5, 10 and 20 %) respectively.
Results showed that, there were decreased significant differences (P ≤0.05) between positive control with other all groups except fresh parsley at level 5%. On the other hand there were no significant differences (P<0.05) between negative control, drug group and dried parsley at level 20%. Also, between dried parsley at level 10% and fresh parsley at level 5% with other al groups under study.
from our results it could be notice that, there were decreased significnt differences (P≤0.05) between positive control and dried parsley at level 5% VS. negative control , fresh parsley at level 20% and dried parsley at two levels (10 and 20%). Besides that, there were no significant differences (P <0.05) between fresh parsley at level 5% with other all groups under study for VLDL-c.
Concerning our results for AI showed that there were decreased significant differences (P ≤0.05) between positive control with other all groups under study. Also, between dried parsley at level 5% VS. negative and positive control, drug group and dried parsley at level20%. While,
there were no significant differences(p<0.05) between fresh parsley at level 5% with other all groups under study except positive control. Values of mean±SD were1.07±0.76, 2.62±0.52, 1.20±0.25, 1.44±0.47, 1.65±0.28, 1.75±0.40, 1.93±0.62, 1.72±0.34and 1.35±0.33mg/dl for negative and positive control, drug group and fresh and dried parsley at three levels (5, 10 and 20 %) respectively.
6-Triglycerides and Total Cholesterols:
Results of serum T. cholestrol showed that, there were decreased significant differences (p≤0. 05) between positive control VS. negative control, drug group, fresh parsley at level 20% and dried parsley at two levels (10 and 20 %). On the other hand, there were no significant differences (P<0.05) between positive control, fresh parsley at two levels (5and10%) and dried parsley at level 5%. Also, between negative control , fresh parsley at level 5% , dried parsley at two levels (10 and 20%) and drug group.
Concerning results for serum Triglycerides showed that, there were decreased significant differences (p≤0.05) between positive control with other all groups except fresh and dried parsley at level 5%. On the other hand, there were no significant differences (P<0.05) between fresh parsley at level 5% with other all groups. Also, between negative control, drug group and fresh parsley at two levels (10 and 20 %). Values of mean± SD were 60.43±3.52, 86.83±9.52, 66.53±20.83, 73.72±7.53, 66.06±16.53, 64.60±15.65, 81.42±8.37, 65.47±9.59 and 60.88±8.87 mg/dl for negative and positive control, drug group and fresh and dried parsley at three levels (5, 10 and 20%) respectively.
7.Effect of time on lipid profile
Results showed the effect of time(0,4 and8 weeks) on kidney functions (Total protein, Albumin, Globulin , Urea and AI).The values of
means ± SD were 6.40±0.08, 7.38±7.78and 7.11±7.41 mg/dl for (0 ,4 and 8) weeks respectively. There were increased significant differences (P≤ 0.05) between (4and 8 weeks) VS. zero time of total protein.
Results for serum albumin showed that, there were increased significant differences (P≤0.05) between (4 and 8 weeks ) VS zero time .
Concerning the same table (20) results showed that, there were no significant differences (P>0.05) between (0,4 and 8 weeks) for serum globulin.
The values of Mean ±SD serum urea were 19.8±0.12, 34.54±0.30 and 34.22±0.14 mg/dl for (0, 4 and 8) weeks respectively. from the above results found that, there were increased significant differences (P≤ 0.05) between (4 and 8 weeks) VS. zero time .
Results for A/G ratio showed that, there were no significant differences (P< 0.05) between groups (0, 4 and 8 weeks).
8. Effect of time on liver functions
Concerning the effect of time (0,4 and 8 weeks ) on liver function (ALK, ALT , AST and Bilirubin). The results showed that, there were decreased significant differences (P≤0.05) between all groups in serum ALK at (4 and 8 weeks) VS. zero time .
Moreover, the effect of time results for ALT there were decearsed significant differences (P≤ 0.05) between ( 0, 4 and 8 weeks). The values of mean ± SD were117.66±0.487, 23.51±6.26, 26.89±6.51mg/dl respectively.
Concerning serum AST results in the same table(21) showed that, there were decreased significant differences (P≤ 0.05) between ( 4and 8 weeks) VS. zero time.
The effect of time on serum bilirubin there was increased significant differences (P≤ 0.05) between (4and 8 weeks) VS. zero time.
9. Effect of time on kidney functions
The results showed the effect of time (0, 4 and 8 weeks) on Lipid profiles (HDL-c, LDL-c, VLDL-c and Atherogenicindex ) . The results for HDL-c showed that, there were no significant differences (P>0.05) between (0,4 and 8 weeks) time wasn,t affect on results. Values of mean±SD were 53.00±0.00, 50.00±5.94 and 53.40±10.33 mg/dl respectively.
Concerning results for LDL-c serum showed that, there were increased significant differences (P≤ 0.05) between (4 and 8weeks) VS. zero time.
Results for VLDL-c showed that there were increased significant differences (P≤ 0.05) between (4 and 8 weeks) VS. zero time.
Moreover results showed that, there were increased significant differences (P≤ 0.05) between (4 and 8 weeks) VS. zero time for Atherogenic index.
10. Effect of time on T. Cholestrol and Triglycerides
Results showed the effect of time (0, 4 and 8 weeks) on T. cholesterol and triglycerides. Concerning results of serum T. cholesterol found that, there were increased significant differences (P≤0.05) between (4 and 8 weeks) VS. zero time.
Results for serum triglycerides showed that, there were increased significant differences (P≤ 0.05) between (4 and 8 weeks) VS. zero time, the values of mean± SD 71.41±11.16 and 67.25±15.38 VS. 50.33±1.27 mg/dl respectively.