الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
 |  | from | 141 |  |  |
| | | from | 141 | | |
Abstract
The jaundice is a condition caused by the release of a large amount of bilirubin in the
blood, which accumulate in the tissue under the skin, and the outer fibrous cover of the
eye, which leads to yellowing of the skin and eyes.
Symptoms of jaundice
The jaundice has several signs, the most common of which are the yellowing of the
skin and the eyes, and the membranes become mucosal to yellow. The stool becomes pale.
The urine becomes dark.
Types of jaundice
There are three types of jaundice:
Pre-hepatic jaundice: This type of disorder occurs before the transfer of bilirubin
from blood to the liver. Causes of this type are sickle cell anemia and hemolytic anemia.
Hepatocellular jaundice: This type is also called hepatic jaundice, in this case ,the
disorder or malfunction is within the liver, the most prominent cause of this type is Gilbert
syndrome, or cirrhosis.
Post-hepatic jaundice: It is also called obstructive jaundice. It is a type of jaundice
resulting from obstruction of bile flow from the liver to the stomach leading to a
redirection of excess bile to the blood. Its causes are Gallstones - inflammation - tumors -
trauma - pancreatic cancer - narrowing of the bile duct - congenital malformations
There is no drug treatment for jaundice, but appropriate antibiotics can be used if the
cause of the inflammation is not to coexist with the disease. It is advisable to take an
appropriate amount of fluids, usually given by vein, in addition to the use of antibiotics
when needed.
Summary
102
The disease leads to many complications if not treated immediately so it is advised
to correct the disease before the occurrence of complications as well. These complications
include: - Liver and gallbladder damage - Blood clots - Cirrhosis of the liver - Septicemia -
Malabsorption syndrome.
Previous studies have focused on avoiding the occurrence of the disease where it is
recommended to treat any narrowing of the channels of gallbladder and liver before a
complete blockage.
Inflammation and oxidative stress play an important role in obstructive jaundice
associated complications where Obstructive jaundice (OJ) produces profound changes in
other organ systems, including the liver, kidneys, heart, brain, blood coagulation and
altered body immunity.
The aim of this study is to examine the effect of alpha lipoic acid and n-acetyl
cysteine alone or in combination on the oxidative stress, inflammation and apoptosis
caused by obstructive jaundice in the blood, as well as their effect on the heart and liver
tissues.
The present work was carried out on 48 male albino rats 55 days old, weighing
between (110 to 130 g). Rats were obtained from the animal house of Medical Research
Institute and were kept under standard conditions of light and temperature for minimum of
one week prior to experimentation for acclimatization and to ensure normal growth and
behavior. They were allowed free access to water and food. Use of experimental animals in
the study protocol was carried out in accordance with the ethical guidelines of the Medical
Research Institute, Alexandria University.
Drugs
The following drugs were used in the present study:
1- N-acetyl cysteine (sigma Aldrich chemical cost Louis. USA)
2- Alpha lipoic acid (sigma Aldrich chemical cost Louis. USA)
Summary
103
Experimental design
The rats were randomly divided into groups
group I (Normal control): Eight normal male rats were received saline at alkaline
pH 7.8
group II (Bile duct ligated): Thirty-two normal male rats had bile duct ligation, which
were performed under anesthesia. A central upper abdominal incision was made, and the
common bile duct was identified, doubly ligated with 410 silk ligatures and was divided. At
the end of the procedure, the abdomen was closed, and the animals could recover.
group III (sham operated): Eight animals were operated on as above, but the
common bile duct was identified and freed from the surrounding tissue without ligation
and division.
Once animals of group II were developed abdominal jaundice, they were randomly
divided to the following groups:
group ΙV: Eight rats were received the solvent (saline at alkaline pH 7.8).
group V: Eight rats were treated with N-acetyl cysteine dissolved in saline in a
dosage of 100 mg/kg/day orally.
group VI: Eight rats were treated with Alpha lipoic acid in a dosage of 25mg/kg
/day SC. The drug was diluted in saline at alkaline pH 7.8
group VII: Eight animals were received combination of both N-acetyl cysteine in a
dosage of 100 mg/kg/day and Alpha lipoic acid in a dosage of 25 mg/kg/day.
Tested drugs will be administered for fourteen days, starting seven days after the bile
duct ligation.
At the end of the treatment period, rats were anesthetized, and blood samples were
collected to determine the following parameters of the serum:
Liver enzymes, bilirubin and alkaline phosphate
Summary
104
After collecting the blood directly, the liver and heart were separated and washed
with a cold salt solution. The samples were stored to measure the following:
Malondialdehyde as an indicator of lipid peroxidation, reduced glutathione level,
glutathione peroxidase activity and superoxide dismutase activity to evaluate the
antioxidant defense capacity, tumor necrosis factor representing inflammatory
cytokines, caspase-3 activity as indicator of apoptosis.
The results of this study showed clearly that the incidence of obstructive jaundice
was accompanied by a statistically significant increase in hepatic enzymes, bilirubin and
alkaline phosphatase. These results indicate the harmful effects of obstructive jaundice in
hepatic and cardiac tissues.
The results also revealed that experimental obstructive jaundice was accompanied by
an oxidative condition that showed increased of malondialdehyde in the liver and heart,
reduced levels of glutathione, and decreased in both glutathione peroxidase and superoxide
dismutase activities in the liver and heart. Moreover, signs of inflammation such as tumor
necrosis factor increased significantly, and this was accompanied by a significantly
increase of caspase-3 activity as a sign of apoptosis.
Alpha lipoic and N-acetyl cysteine alone showed statistically significant
improvement in liver enzymes, decreased bilirubin level, decreased alkaline phosphatase
activity. When combined, both achieved significant therapeutic progress by reducing the
risk oxidative stress, inflammation and apoptosis in hepatic and cardiac tissues of
obstructive jaundiced rats. However, the effect of N-acetyl-cysteine was superior to that of
Alpha lipoicacid.
In conclusion, the present study provided the first evidence for the potential
protective effect of combination the Alpha lipoic acid with N-acetyl cysteine against
obstructive jaundice-induced inflammation, oxidative stress, and apoptosis.
However, the anti-inflammatory, anti-oxidative and anti-apoptotic effects of the
combination therapy were more substantial than those offered by each drug alone. More
comprehensive studies are needed to evaluate and clarify usefulness of this combined
therapy in clinical situations.