الفهرس 
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Abstract
Exposure to environmental factors either biological e.g., bilharzial infection or chemical e.g., chlorpyrifos as an example of pesticides, has been associated with the production of reactive oxygen species (ROS). ROS are capable of producing lipid peroxidation and consequently can cause damage to cellular macromolecules e.g., protein, RNA and DNA. In this aspect, antioxidants play an important role in protecting cellular components against ROS-induced damages. The first antioxidant defence line is GSH and its related enzymes GPx and GRd. Thus, they play a very important role in protecting cellular macromolecules. Since exposure to ROS lead to GSH depletion, it is of great importance to enhance intracellular GSH level. Oxothiazolidine (OTC), a cysteine prodrug, has been found to increase intracellular GSH level. Furthermore, the level of TNF-α , a proinflammatory cytokine, has been affected by the redox status of the cell. Accordingly, its level is influenced by OTC which has been found to inhibit the production of some cytokines.
Accordingly , the present study was under taken to investigate the possible protective role of OTC against ROS-produced as result of chlorpyrifos exposure in S. mansoni infected mice.
Hepatic concentration levels of GSH and TNF-α. as well as the enzymatic activity levels were measured in control, oil control, CPS-Schisto and CPS-Schisto-OTC groups in different time intervals 24 hrs in addition to 2, 4, 8 and 12 weeks post CPS treatment. OTC treatment has started 24 hrs just before CPS treatment. Meanwhile histopathological studies were carried to correlate histopathological changes with biochemical changes.
The results of the present work showed that time intervals can be divided into 3 stages in which 24 hrs and 2 weeks-post CPS represent the first stage. In this stage, the depletion of GSH and the increased levels of TNF-α could be attributed mainly to the effect of CPS exposure rather than S. mansoni infection.
The second stage include 4 and 8 weeks post CPS treatment. In this stage the histopathological result revealed the formation of granuloma. This is accompanied by the production and liberation of ROS. Accordingly, this observed decrease in GSH levels could be attributed to its consumption by the produced ROS. Thus , the depletion of GSH and increased levels of TNF-α could be attributed mainly to S. mansoni infection.
The third stage include the 12 week post CPS treatment. In this time interval the observed biochemical changes could be attributed to both CPS treatment and S. mansoni infection.
Meanwhile, in OTC treated group, although the GSH level were lower than that in control group but higher than that in CPS-Schisto group. Inversely, the TNF-α levels were higher than that in control group but lower than that in CPS –Schisto group.
Histopathologically, the degree and the frequency of pathological changes in OTC treated group were slower than that in CPS –Schisto group. Thus, enhancement of intercellular GSH levels by OTC treatment lead to the observed low levels of TNF-α and slowed down the histopathological changes. Therefore, the data of the present study may support the suggestion that OTC can be useful in the treatment of toxicities due to exposure to hepatotoxic compound e.g. chlorpyrifos and in certain disease as in S. mansoni infection.