الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Schistosomiasis, is a disease caused by parasitic worms of the genus Schistosoma, it is a significant cause of illness and death in the developing world and its global burden has been significantly underestimated. More than 779 million of people in 76 countries of the world were considered to be at risk of acquiring schistosomiasis and 207 million individuals were infected. More than half of them had some kind of morbidity and approximately 20 million people suffered from severe consequences of chronic infection.
Most pathology is attributed to the CD4+ Th2-driven, granulomatous response to schistosome eggs and their antigens. As granulomas evolve, collagen fibers are deposited around the eggs, a process that leads to fibrosis, which is characterized by net accumulation of an extracellular matrix, including collagen, glycoproteins and proteoglycans. Consequently the Th2 cytokines dominate and liver fibrosis increases dramatically. Cytokines induce Kupffer cells to produce TGFβ 1, furthermore the granulomatous inflammatory process induce activation of adjacent hepatic stellate cells which play important roles in the pathogenesis of liver fibrosis.
Liver fibrosis is a disease characterized by excessive deposition of extracellular matrix in the liver during chronic injury. This disease has many causes such as parasitic infection, viruses, chronic alcohol consumption, ischemia, toxins and nonalcoholic steatohepatitis.
HSCs are the main ECM producing cells in the injured liver, following chronic injury, HSCs activate or transdifferentiate into myofibroblast like cells, acquiring contractile, proinflammatory, and fibrogenic properties. HSCs activation consists of 2 major phases: (1) initiation (also called a pre-inflammatory stage) and (2) perpetuation which include proliferation, chemotaxis, fibrogenesis, contractility, matrix degradation, release of pro-inflammatory cytokines and retinoid loss.
Damaged hepatocytes and activated Kupffer cells not only secrete reactive oxygen species, but also produce pro-inflammatory and profibrogenic cytokines such as tumor necrosis factor-α, interleukins and transforming growth factor-β1. Paracrine signaling of HSC by these stimuli results in the conversion of quiescent HSC into proliferative, fibrogenic and contractile myofibroblasts which begin to secrete large amounts of ECM proteins including fibronectin, collagen (types I, III and IV), undulin, elastin, laminin and desmin.
Resveratrol (3, 4′, 5- trihydroxy-trans-stilbene), a natural polyphenol found mainly in grapes and peanut, has been reported to have a wide range of biological properties. The potent antioxidant activity of Resveratrol is well established in the literature, however, evidence has demonstrated that this compound also possesses anti-inflammatory, antiaggregant and neuroprotective properties. The mechanisms underlying the beneficial effects of Resveratrol are not totally elucidated, but have been related mainly to its antioxidant activity that has demonstrated to protect tissues against a variety of damage caused by oxidative stress.
The present experimental study was carried out to investigate the protective effect of Resveratrol as anti-oxidant, anti-inflammatory through improvement of liver enzymes, lipid peroxidation, serum TNFα and morphological histology of the liver in schistosomal fibrosis liver in murine model.
This study was conducted on 60 male albino mice CD1 species; with a body weight ranging from 18-22 g. Throughout the experimental period (10 weeks), animals had free access to food and water. They were divided into four main groups:
Group Ι: Included 15 mice represented as (Normal Untreated group).
Group ΙΙ: Included 15 mice represented as (Normal treated group).
These mice injected intraperitoneally with Resveratrol (20mg/kg twice/week), treatment started by the end of the fourth week till the end of the study.
Group Ш: 15 mice, each mouse infected percutaneously with ± 80 schistosoma mansoni cercariae. Then coninuoued untreated till the end of the study, represented as (Infected untreated group).
Group IV: Consisted of 15 mice, each mouse infected percutaneously with ± 80 schistosoma mansoni cercariae and treated with Resveratrol (20mg/kg twice/week) which started by the end of the fourth week and continued till the end of the study, represented as ( Infected treated group).
At the end of the experimental period: 1- Blood samples were collected and serum was separated by centrifugation for measuring: serum aspartate aminotransferase, alanine aminotransferase, and serum TNFα using ELISA kit.
2- Liver sampling: After removal of the liver from each mouse, the ventral median lobe of the liver was fixed in 10% neutral buffered formalin for histopathological study. The remaining portion was homogenized and used for measuring MDA level and PCR for gene expression of Fibronectin.
Regarding liver enzymes levels, there was significant increase in the infected untreated group as compared to the normal control group and treatment of Resveratrol significantly reduced the enzymatic elevation. There was no significant difference between the infected treated and normal control groups and so the normal treated group showed no significant difference as compared to the normal group.
Tumor necrosis factor alpha levels, measured by enzyme immunoassay, in the infected untreated group there were significantly increased compared to the normal control group, while administration of Resveratrol in the infected treated group resulted in a significant decrease of TNFα level, meanwhile, the levels of TNFα in the normal treated group showed no significant difference as compared to the normal control group.
Histological studies of the liver, revealed that S.mansoni infection caused multiple granulomas surrounded with laminated layers of fibrosis, with hepatocytes necrosis as compared with normal architecture of the normal control group, Resveratrol treatment improved the histopathological alterations caused by infection in the infected group. In addition the normal treated group showed no differences as compared to the normal control group.
Infection of mice with S.mansoni resulted in a significant increase in lipidperoxidation as measured by MDA level in liver homogenate, however Resveratrol when administrated to the infected treated group, MDA levels significantly decreased back to the normal control mice. In addition to this, there was significant decrease of MDA level in normal treated mice as compared to the normal control group which suggested the potent anti-oxidant capabilities of this natural polyphenolic Resveratrol.
As regard the gene expression of Fibronectin, there was significant increase of Fibronectin expression in the infected untreated group, and this elevation was significantly decreased nearly to the normal control group after Resveratrol treatment. There were no significant differences in Fibronectin expression between infected treated and normal control groups, which suggested antifibrotic activity of Resveratrol.