الفهرس 
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Abstract
” Renal ischemic reperfusion (I/R) is a common clinical event that disrupts the homeostasis of kidney cell function, which is leading to unacceptable high morbidity and mortality. There is evidence that heterogeneity of blood flow plays an important role in the pathophysiology of l/R. During I/R injury, there is an intense and persistent renal vasoconstriction that reduces overall kidney blood flow to approx. 50% of normal. Thalidomide was first introduced in the late 1950s for the prevention of morning sickness in pregnant women, recently thalidomide has been found to have anti-angiogenesis and ante-inflammatory properties, and based on these observations thalidomide has been used as a therapeutic reagent in some malignant tumor including liver cancer, renal cell carcinoma, and breast cancer. The main task of this study was investigated the effect of pretreatment with thalix and thalixisosteres 3a-f on renal function, angiogenesis VEGF, MDA (Malondialdehyde) (a marker of lipid peroxidation), SOD (Superoxide dismutase) (a marker of antioxidant enzyme), and GSH (Glutathione) (a marker of non-enzymatic antioxidant). Experimental design This study was carried out on Fifty-four male Sprague-Dawley rats 180-200 gm.; 3-4 months old. Rats were housed in separate metal cages under the same constant environmental and nutritional condition through the period of investigation. Rats were classified as follows: 1) Negative control group. 2) Positive ischemic/reperfusion control group mice suffered 45 min left renal ischemia tracked by clamp relief 3) thalix treated ischemic/ reperfusion group, rats obtained thalidomide (thalix) (1000 IU/kg, SC) 24 h before the operative method and continued daily till the day of sacrifice. and from 4) to 9) thalixisostere from 3a to 3f treated ischemic/ reperfusion group rats received thalixisostere from 3a to 3f (1000 IU/kg, SC) 24 h before the operative method and continued every day till the day of sacrifice All rats with renal ischemic/reperfusion were subjected to serum analysis before surgery and 3days after renal ischemia/Reperfusion induction (n=6) for each group The results shows • There was an insignificant change in the body weight in all groups before (P = 0.427). There was a significant decrease in all I/R groups’ final body weight compared to a negative control group (P=0.01). • There was a significant increase in creatinine from all I/R treated with thalixisosteres 3a-3f groups as compared to negative and positive control groups (P≤0.01). Also, there was an insignificant difference in creatinine from I/R treated with thalixisosteres 3a-3f groups compared to I/R treated with thalix groups (P>0.05). • There was a significant increase in urea from all I/R treated with thalix and thalixisosteres 3a-3f groups compared to negative control and positive control groups (P≤0.01). There were insignificant differences in urea from all I/R treated with thalixisosteres 3a-3f groups as compared to thalix groups (P>0.05). • There was a significant increase in the mean concentration of MDA in kidney tissue obtained from all I/R treated with thalix and thalixisosteres 3a-3f groups as compared to a negative control group (P≤0.01). The mean MDA concentrations in kidney tissue of all I/R treated with thalix and thalixisosteres 3a-3f were significantly lower than that in positive control group (P≤0.01). Also, there was a significant increase in MDA concentrations in kidney tissue from I/R treated with thalixisosteres 3a-3e groups as compared to I/R treated with thalixisosteres 3f group (P≤0.05). • There was a significant decrease in the mean activity of SOD in kidney tissue samples obtained from all I/R treated with thalix and thalixisosteres 3a-3f groups compared to a negative control group (P ≤ 0.01). Moreover, there was a significant increase in the mean activity of SOD in kidney tissue samples from all I/R treated with thalix and thalixisosteres 3a-3f groups as compared with positive control groups (P < 0.01). In addition, the mean SOD activity in kidney tissue of I/R treated with thalixisosteres 3a-3e groups was significantly decreased compared to I/R treated with thalixisosteres 3f group (P≤0.01). • There was a significant decrease in the mean concentrations of GSH in kidney tissue samples obtained from all I/R treated with thalix and thalixisosteres 3a3f groups compared to a negative control group (P ≤ 0.01). Moreover, there was a significant increase in the mean concentrations of GSH in kidney tissue samples from all I/R treated with thalix and thalixisosteres 3a-3f compared with positive control groups (P ≤ 0.01). In addition, mean concentrations of GSH in kidney tissue of I/R treated with thalixisosteres 3a-3e groups were significantly decreased compared to I/R treated with thalixisosteres 3f group (P≤0.01). • There were insignificant differences in VEGF obtained from all I/R treated with thalix and thalixisosteres 3a-3e groups compared to a negative control group (P > 0.05). On the other hand, there were insignificant differences in VEGF from thalixisosteres 3a-3e groups compared with thalix groups (P >0.05). Moreover, there was a significant decrease in the mean VEGF from I/R treated with thalixisosteres 3f groups compared with negative and positive control groups (P ≤ 0.001). In addition, the mean concentrations of VEGF of I/R treated with thalixisosteres 3a-3e groups were significantly increased compared to I/R treated with thalixisosteres 3f group (P≤0.001). In conclusion: Consistent with the laboratory findings, this new thalix (halixisosteres 3f) reduce the formation VEGF. These findings suggest that new thalix is more effective than thalix in the inhibition of the expression VEGF as pro-angiogenic factors. The present study, to the best of our knowledge, is the first study to exhibit antiangiogenic activity of new thalix in I/R-induced renal injury.”