الفهرس 
? INTRODUCTION AND AIM OF THE WORKOnly 14 pages are availabe for public view
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Abstract
he liver is the major organ responsible for biotransformation of drugs and toxic compounds. It is more vulnerable to toxic and chemical injury than many other organs.
The present study is conducted to investigate the possible protective and curative effects of a natural licorice extract, GL, on Lipopolysaccharide (LPS) and D-galactosamine (D-GAIN) induced hepatotocellular injury in rats as a well-established experimental model of acute hepatitis. The model takes advantage of the ability of a transcriptional inhibitor, DDGAIN, to potentiate the toxic effects of LPS, producing typical hepatocellular necrosis and apoptosis followed by acute fulminant hepatitis. Not only the study investigated the effect of glycyrrhizin on acute hepatic injury, but also the different mechanisms of protection, and the effect of glycyrrhizin on both apoptosis and inflammation.
To display the role of GL in this liver injury model, thirty male albino rats, weighing 150-200g at the age of 8-10 weeks, were kept in plastic cages and given free access to food and water. Rats were divided equally and randomly in five groups. Group one was the control group, Group two, was the hepatitis model that was injected intravenously with LPS/D-GAlN in a dose of (50 !lg/kg body weight for LPS and 300 mg/kg body weight for D-GAlN). Group three was treated intravenously with GL in a dose of 100 mg /kg body weight, half an hour before LPS/D-GAlN injection. Group four and five were also intravenously injected with GL, with the same dose, but half an hour and four hours after LPS/D-GAlN administration respectively. Then these animals were killed by decapitation under light halothane anesthesia, 8 hours after LPS/D-GAlN injection. Blood samples were taken by cardiac puncture to measure the serum level of liver enzymes (aminotransferases), and livers were rapidly removed intact and processed differently for, histological and immunohistochemical studies.
• In hematoxylin-eosin sections, LPS/D-GAlN administration caused marked
hepatocellular degeneration, hemorrhage, congestion and inflammatory cell infiltration. Many hepatocytes also exhibited apoptosis-like features. Pretreatment with GL significantly improved this microscopic picture as livers were appeared morphologically with nearly
normal structure. While post-treatment with GL also reduce the effects of LPS/D-GAIN, but this reduction decreased with the time of administration.
• By using charcoal for labeling the liver macrophages, hematoxylin-eosin
sections showed that GL attenuated the marked increase in the charcoal labeled cells induced by LPS/D-GAIN administration. With maximum decrease on GL pretreatment and little difference between the two groups ofGL post-treatment.
• Immunohistochemical studies showed obvious high immunoreactivity for
activated caspase 3 and TNF-a in liver sections on administration of LPS/D-GAIN that was attenuated by GL co-treatment. GL pretreatment showed the least immunoreactivity for both followed by GL half an hour post-treatment. GL four hours post-treatment caused only some decrease in the immunoreactivity for TNF-a in comparison to LPS/D-GAIN group.
• The results of serum liver enzymes (AL T and AST) were in harmony with the
light microscopic pictures. Their level highly increased by LPS/D-GAIN injection, indicating hepatocellular damage, but markedly lowered by GL especially when injected half an hour before LPS/D-GAIN administration.
Consequently, the above data indicated the role of GL in the treatment of the acute hepatitis model (LPS/D-GAIN) by its lowering effect on serum liver enzymes. It seems that GL pretreatment is more effective than post-treatment where the .efficacy of GL decrease with time (group four better than group five). Various mechanisms ofliver protection against liver injury, including LPS/D-GAIN induced hepatitis, were known. The current results attributed GL hepatoprotective effect mainly to the suppression of hepatic TNF-a and active caspase 3, leading to inhibition of apoptosis, necrosis and damage induced by inflammatory cell infiltration, in addition to GL lowering effect on macrophage recruitment and activity.
It is fairly to mention that one study is not capable of interpretating the hepatoprotective effect for such substance, with multiple mechanisms and diverse actions that are not completely elucidated till now. Thus, other possible mechanisms can not be ruled out and further studies are still required to clarifY this point in further details.
In conclusion, the results of the present study provide evidence for the protective and curative effect of GL against LPS/D-GAIN -induced hepatotoxicity in rats. The anti-
inflammatory and anti-apoptotic effects of GL were also evident in this study. These results should thus provide a new insight in treating patients with acute hepatitis and paves the future for a new rationale in the treatment of liver diseases. However further experimental studies are still needed for more details about GL as a drug for acute hepatitis.