الفهرس 
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Abstract
Effect of cholesterol induced hypercholesterolemia on some biochemical blood parameter and their modulation with L-carnitine in rabbits were investigated. This study investigated the harmful effects of cholesterol on several biochemical blood parameters in white male New-Zealand rabbits exposed to rich cholesterol diets for sixty days. Moreover, evaluation of the possible protective effects of L-carnitine administration on some blood constituents and heart in male rabbits exposed to rich cholesterol diet The study was conducted on fifty white male New Zealand rabbits of 2-3 months old and of average body weight ( 2.0-3.0 kg ). Rabbits were housed in separate metal cages and kept at constant environmental and nutritional conditions throughout the periods of the experiment.
The rabbits were randomly divided into five main equal groups one control and four experimental groups placed in individual cages and classified as follows:
Group I: ( Control group ).
Comprised ten rabbits, were fed on normal diet and received no drugs, served as control for all experimental groups.
Group II: (L-Carnitine treated group).
Included ten rabbits, were fed on normal diet and received of L-Carnitine was given orally and daily at a normal dose.
Group III: Cholesterol exposed group ).
Consisted of ten rabbits, received cholesterol rich diet.
Group IV: ( Cholesterol + normal dose of L-Carnitine ).
Comprised ten rabbits, exposed to cholesterol rich diet and administered daily with L-Carnitine at normal dose level.
Group V: ( Cholesterol + double dose L-Camitine ).
Included ten rabbits, fed with cholesterol rich diet and treated daily with double dose of L-Carnitine.
After overnight fasting, blood samples were collected by vein puncture of the marginal ear veins after pronning the rabbits from all animal groups (control and experiment groups) three times along the duration of experiment, at 30, 45 and 60 days from the onset of rabbits exposed to cholesterol and administered with L-Carnitine.
Approximately 6.0 ml of blood were obtained from all groups ( control and experimental groups ), and divided to two part:
1)1.0 ml taken in clean dry screw-capped tubes, then allowed to coagulate at room temperature for 30 minutes. then centrifuged at 3000 r.p.m for 10 minutes. The clean clear serum was separated and received in dry sterile sample tune using sterilized pipettes then kept at 2 to 5°C until used for
subsequent carry out lipoprotein electrophoresis.
2)Heparinized blood samples for plasma separation were collected in clean dry screw-capped tubes, and plasma was separated by centrifugation at 3000 r.p.m. for 10 minutes. The clean, clear plasma was separated and received in dry sterile sample tubes using sterilized pipettes and processed directly for determination of Lipoprotein Lipase (LPL) and Lecithin Cholesterol Acyltransferase ( LCAT ) activities, then kept in a deep freeze at —20°C until used for subsequent biochemical analysis.
All plasma samples were analyzed for the following biochemical parameters:
Total Lipids (TL), Total Cholesterol (TC) , Triacylglycerols (TGs), Phospholipids (PLs), Non esterifies Fatty Acids ( NEFA ), High-density lipoproteins cholesterol ( HDL-C ), Low-density lipoproteins cholesterol ( LDL-C ) and Very low-density lipoproteins cholesterol (VLDL-C ).
Moreover, after plasma separation, erythrocytes were washed for plasma membrane isolation and processed for determination of :
Total Cholesterol, Triacylglycerols, Phospholipids and Fatty acids composition of Erythrocyte membrane
Hearts were taken one time from each group of the rabbits after had been sacrificed at the end of the experiment, the hearts were immediately removed and washed several times with saline and blotted between two damp filter papers, and carefully examined by naked eye for detection of any abnormalities. and immediately fixed in 10% neutral buffered formaline for histopathological finding.
The obtained results summarized as follows:-
1- Plasma total lipds:
Rabbits fed on normal diet with L-carnitine showed a significant decrease in plasma total lipids concentration allover the periods of the experiment, While a significant increase in plasma total lipids concentration was observed in group fed on cholesterol rich diet during all the periods of the experiment when compared with the control group.
A significant decrease in plasma total lipids concentration was observed in group fed on cholesterol rich diets with normal dose of L-carnitine and cholesterol rich diet with double dose of L-carnitine during all the periods of the experiment, when compared with cholesterol rich diet group.
Plasma total lipids concentration in cholesterol rich diet supplied with double dose of L-carnitine was signficantly decreased during all the periods of the experiment, when compared with cholesterol rich diets supplied with normal dose of L-carnitine.
2-Plasma total cholesterol:
In cholesterol exposed rabbits plasma total cholesterol concentration showed a significant increase allover the periods of the expiremint, when compared with the control group.
While, administration of L-Carnitine by normal and double dose in cholesterol exposed rabbits exhibited a significant decrease in plasma total cholesterol concentration during all the periods of the experiment, when compared with cholesterol rich diet group.
3-Plasma Triacylglycerols:
Adminstration of L-Carnitine in normal diet feeding rabbit resulted in a significant decrease in plasma triacylglycerols concentration after 30 and 45 days of experiment. While, a significant increase in plasma triacylglycerols concentration was observed in cholesterol rich diet group during all the periods of the experiment, when compared with the control group.
On the other hand a significant decrease in plasma triacylglycerols concentration was recorded in group fed on cholesterol rich diet supplied with normal dose and that supplied with double dose of L-Carnitine compard with cholesterol rich diet group.
Moreover, plasma triacylglycerols concentration in cholesterol rich diet with double dose of L-carnitine supplemented group was signficantly decreased during all the periods of the experiment when compared with cholesterol rich diet with normal dose of L-carnitine.
4-Plasma Phospholipids:
A significant increase in plasma phospholipids concentration was observed in group fed on cholesterol rich diet as compared to the control group.
A significant decrease in plasma phospholipids concentration was observed in cholesterol rich diet with normal and double dose of L-carnitine supplemented groups allover the periods of the experiment, when compared
with cholesterol rich diet group.
Plasma phospholipids concentration in rabbit fed on cholesterol rich diet supplied with double dose of L-carnitine was signficantly allover the periods of the experiment, when compared with rabbits fed on cholesterol rich diet supplied with normal dose L-carnitine.
5- Plasma non esterfied fatty acid ( NEFA) :
L-Carnitine supplementation in normal diet fed rabbits showed significat increase in plasma NEFA concentration. While, in cholesterol rich diet supplemented group a significant decrease in plasma NEFA concentration was observed during all the periods of the experiment, when compared with
the control group.
A significant increase in plasma NEFA concentration was observed in cholesterol rich diet with normal dose of L-carnitine supplemented group and that with double dose of L-carnitine during all the periods of the experiment, when compared with cholesterol rich diet group.
Plasma NEFA concentration in cholesterol rich diet with double dose of L-carnitine supplemented group was signficantly increased allover the periods of the experiment. when compared with cholesterol rich diet with normal dose
of L-carnitine.
6- Plasma High-density lipoproteins cholesterol ( HDL-C ):
A significant increase in plasma HDL-C concentration was observed in cholesterol rich diet group after 60 days of the experiment, when compared
with the control group.
7-Plasma Low-density lipoproteins cholesterol (LDL-C ):
A significant increase in plasma LDL-C concentration was observed in group fed on cholesterol rich diet allover the periods of the experiment, when compared with the control group.
A significant decrease in plasma LDL-C concentration was recorded in cholesterol rich diets supplied with normal dose of L-carnitine and cholesterol rich diet with double dose of L-carnitine supplemented groups during all the periods of the experiment, when compared with cholesterol rich diet group.
Plasma LDL-C concentration in rabbits fed on cholesterol rich diet supplied with double dose of L-carnitine was signficantly decreased during all the periods of the experiment, when compared with cholesterol rich diets with normal dose of L-carnitine supplemented group.
8-Plasma Very low-density lipoproteins cholesterol (VLDL-C ):
A significant decrease in plasma VI,DL-C concentration in normal diets with L-carnitine supplemented group after 30 and 45 days of the experiment. On the other hand a significant increase in plasma VLDL-C concentration was observed in cholesterol rich diet group during all the periods of the experiments when compared with the control group.
A significant decrease in plasma VLDL-C concentration was observed in cholesterol rich diet with normal dose of L-carnitine and that with double dose of L-carnitine supplemented groups during all the periods of the experiment, as compared with cholesterol rich diet group.
Plasma VLDL-C concentration in cholesterol rich diet with normal dose of L-carnitine supplemented group was significantly decreased during all the periods of the experiments when compared with cholesterol rich diets with normal dose of L-carnitine supplemented group
9- Lipoprotein Electrophorisis : Alpha-Lipoprotein percentage ( HDL):
A significant decrease in serum alpha-lipoprotein (HDL) percentage was observed in cholesterol rich diet group allover the periods of the experiment when compared with the control group.
Pre-Beta Lipoprotein percentage (VLDL):
A significant decrease in serum pre-beta lipoprotein (VLDL) percentage was observed in cholesterol rich diet group during all the periods of the experiment, when compared with the control group.
A significant deccrease in serum pre-beta lipoprotein (VLDL) percentage was observed in cholesterol rich diet with normal dose of L-carnitine supplemented group and cholesterol rich diet with double dose of L-carnitine supplemented group during all the periods of the experiment, as compared with cholesterol rich diet group.
Beta Lipoprotein percentage:
In cholesterol exposed rabbits a significant increase in serum beta lipoprotein (LDL) percentage was observed allover the periods of the expermint, in comparison with the control group.
Administration of L-carnitine in normal and double dose in cholesterol exposed rabbits caused significant deccrease in serum pre-beta lipoprotein (LDL) percentage allover the periods of the experiment, This when compared
with cholesterol rich diet.
10- Plasma Lipase Activity:
Administration of L-Carnitine to normal rabbits resulted in a significant increase in plasma lipase activity after 30 and 60 days of the experiment. While in cholesterol exposed animals plasma lipase activity
showed a significant decrease during all the periods of the experiment, as compared with the control group.
On the other hand, treatment of cholesterol exposed rabbits with L-Carnitine in normal and double dose exhibited significant an increase in
plasma lipase activity allover the periods of the experiment, when compared with the control group.
Plasma lipase activity in cholesterol rich diet with double dose of L-carnitine supplemented group was signficantly increased during all the periods
of the experiment, when compared with cholesterol rich diet with normal dose of L-carnitine.
11- Plasma Lecithin Cholesterol Acyl Transferase ( LCAT) activity:
A significant decrease in plasma LCAT activity was observed in L-Carnitine administered rabbits during all the periods of the experiment. On the other hand in cholesterol exposed rabbits plasma LCAT activity showed a
significant increase allover the period of the expermint in comparison with the control group.
A significant decrease in plasma LCAT activity was observed in group fed on cholesterol rich diet with normal dose of L-carnitine supplemented group and cholesterol rich diet with double dose of L-carnitine during all the
periods of the experiment, when compared with the cholesterol rich diet group.
On the other hand, Treatment of cholesterol exposed rabbits with double dose L-Carnitine exhibited significant decrease in plasma LCAT activity allover the period of the experiment, when compared with the normal dose of L-carnitine supplemented group .
In cholesterol exposed rabbits a significant increase in erythrocyte membrane cholesterol concentration was observed allover the periods of the
expermint, when compared with the control group.
A significant decrease of erythrocyte membrane cholesterol was observed in cholesterol rich diet with normal dose of L-carnitine supplemented group and cholesterol rich diet with double dose of L-carnitine supplemented group during all the periods of the experiment, when compared
with cholesterol rich diet group.
13- Triacylglycerols Concentration of Erythrocyte membrane:
In L-carnitine exposed rabits a significant decrease in triacylglycerols concentration of erythrocyte membrane after 30 and 45 days of the experiment, While, a significant increase in triacylglycerols concentration of erythrocyte membrane was observed in cholesterol rich diet group during all the periods of the experiment, when compared with the
control group.
L- Carnitine treatment of cholesterol exposed rabbits caused significant decrease in triacylglycerols concentration of erythrocyte membrane allover the periods of the experiment, when compared with cholesterol rich diet group. On the other hand Triacylglycerols concentration of erythrocyte membrane in cholesterol rich diet with double dose of L-carnitine supplemented group was signficantly decreased during all the periods of the experiment when compared with cholesterol rich diet with normal dose of L-carnitine
supplemented group.
14- Phospholipids Concentration of Erythrocyte membrane:
A significant increase in phospholipids concentration of erythrocyte membrane was observed in cholesterol rich diet group during all the periods of the experiment, when compared with the control group.
While, treatment of cholesterol exposed rabbits by normal and double dose L-Carnitine exhibited a significant decrease in phospholipids concentration of erythrocyte membrane during all the periods of the experiment, when compared with cholesterol rich diet group.
Phospholipids concentration of erythrocyte membrane in cholesterol rich diet with double dose of L-carnitine supplemented group was signficantly decreased during all the periods of the experiments, when compared with cholesterol rich diet with normal dose of L-carnitine supplemented group.
15 — Fatty acid composition percentage iin erythrocyte membrane: Saturated Fatty acids:
Rabbits fed on normal diet with L-Carnitine showed a significant decrease in total percentage of saturated fatty acids in erythrocytes membrane compared with the control group, especially Lauric acid, Myristic acid, Palmitic acid and Stearic acid during all the periods of the experemint. While a significant increase in percentage of Myristic acid and Palmitic acid at all the periods of the experiment as well as an increase in Lauric acid and Stearic acid at 45 and 60 days and increase in Pentadecylic acid at 60 days of the experiment, in rabbits fed with cholesterol rich diet, when compared with the control group. This lead’s to increase the total saturated fatty acids percentage in all periods of the experiment of this group.
On the other hand a significant decrease in total saturated fatty acids percentage was recorded in groups fed on cholesterol rich diet supplied with normal dose and that supplied with double dose of L-Carnitine compard with cholesterol rich diet group. especially, Myristic acid and Palmitic acid
Moreover, total saturated fatty acids percentage in cholesterol rich diet with double dose of L-carnitine supplemented group was signficantly decreased during all the periods of the experemint when compared with cholesterol rich diet with normal dose of L-camitine supplemented group. due to decrease of Palmitic acid percentage.