الفهرس 
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Abstract
Summary
MTX is achemotherapeutic widely used in the treatment of several types of cancer, such as leukemia, rheumatoid arthritisand systemic lupus erythematosus. Silymarinpossess strong antioxidant, anti-inflammatory, and anti-fibrotic properties. It has strong hepatoprotective and neuroprotective effects. BBR plays an important role in metabolic diseases and many other inflammatory diseases. It has antioxidant, anti-inflammatory, hepatoprotective, anti-diabetic and cardioprotective properties.
The current work provided a clue of the possible therapeutic role of BBR and silymarin on MTX induced histopathological changes in the liver. Concomitant treatment of male albino rats with antioxidants has been recently shown to exert a protective effect against MTX-induced hepatotoxicity.
This study, therefore, aimed to investigate, characterize, and compare between the potential protective effect of BBR and silymarin against MTX-induced hepatic dysfunction.
The rats were randomly divided into six groups of five animals each (n=5)
• Control group (group I): (n=5) rats injected 0.5 ml saline as a single IP injection on the first day and 1ml carboxymethylcellulose (CMC-0.5%) by oral gavage daily for 7 days.
• BBR-treated group (group II): (n=5) given 1ml BBR by oral gavage daily.
• Silymarin group (group III): (n=5) given 1 ml of Silymarin by oral gavage daily.
• MTX-treated group (group IV): given 0.5 ml of MTX single IP injection.
• MTX+ BBR-treated group (group V): (n=5) given 0.5 ml of MTX single IP injection and 1ml BBR by oral gavage daily.
• MTX+ Silymarin-treated group (group VI): (n=5) given 0.5 ml of MTX single IP injectionand 1 ml of Silymarin by oral gavage daily.
After 7 days of therapy, the animals were sedated with urethane, sacrificed and their livers were obtained. Each liver was processed for histological and ultrastructural examinations.
The results of examination of the liversections of group I, group II and group III by light microscope and transmission electron microscope were like the normal structure.
Resultsof group IVshowedsignificant histopathological changes in the liver. H and E-stained sections showed loss of the normal architecture of the liver. There were dilatation and congestion of central vein and portal vein. There were thickened connective tissue septa and dilated congested blood vessels. Apoptotic hepatocytes were distinguished by dense eosinophilic cytoplasm and pyknotic nucleus. Hepatocytes showed cytoplasmic vacuolations and signet ring appearance.Mononuclear cellular infiltration was detected. Masson trichome’s stained liver sections showed massive collagen deposition around central vein and in the portal area. At the ultrastructural levelhepatocyte showed dilatation of rough endoplasmic reticulum cisternae, dark pyknotic irregular nucleus, cytoplasmic vacuolations andan extensive bundle of collagen fibrils.
In group V and group VI, concomitant treatmentwith BBR and silymarineffectively inhibited the MTX inducedliver damage and succeeded inrestoring the liver architecture. H and E-stained sections showedrestoration of the normal histological architecture of the liver. Hepatocytes were radiating from the central vein.Masson trichome’s stained liver sections showed moderate collagen deposition around central vein and in the portal area. At the ultrastructural level hepatocytes showed nearly normal hepatocyte ultrastructure with superiority of silymarin over BBR.