الفهرس 
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Abstract
Ferric-nitrilotriacetic acid (Fe-NTA) being one of the most potent iron pro-oxidant compounds which used in the present study to induce oxidative stress and induction renal carcinoma in rats. Nitrilotriacetic acid is a synthetic tricarboxylic acid which forms water soluble chelate complexes with various metal ions including iron at natural PH. Its iron complex Fe-NTA is a nephrotoxic agent. It induces apoptosis in rats’ renal proximal tubules. The renal toxicity is assumed to be caused by the elevation of serum free iron concentration following its reduction at luminal side of proximal tubule generating ROS leading to enhancement of lipid peroxidation with a concomitant decrease in tissue glutathione level.
Nanotechnology has provided a way for us to rearrange and restructure matter on an atomic scale, allowing us to reach down to the very roots of any problem. There is evidence that zinc is an effective antioxidant and investigated in clinical trials as a cancer chemo preventive agent. Therefore, the purpose of this study was to evaluate the protective effect of biosynthesized zinc nanoparticles (Zn-NPs) synthesized using edible white mushroom Agaricus bisporus against renal cancer induction in rats. To achieve this aim, a total of sixty male wistar rats weighing 120-150 g were used and divided into four groups.
group I (Control; n=15): normal rats were injected orally by gavage with 1ml of physiological saline (9%).
group II (Fe-NTA; n=15): rats were injected intraperitoneally (i.p) twice weekly with Fe-NTA (9 mg/kg body weight) for 16 weeks, in the first week of the experiment rats were injected with diethylnitrosamine (DEN) i.p once with dose (200mg/kg b.w).
group III (ZnNPs; n=15): rats were orally administrated with Zn-NPs (10 µg/kg b.w) day other day three times a week till the end of experiment.
group IV (Zn-NPs+ Fe-NTA; n=15): rats were administrated with Zn-NPs (as in group 3) for 2 weeks, then rats were orally administrated with Zn-NPs (10 µg/kg b.w) day other day three times a week 30 minutes prior to Fe-NTA injection (as in group 2) till the end of experiment 16 weeks.
At the end of the experiment rats were sacrificed under diethylether anesthesia, blood was collected from the heart and a part of kidney tissues samples were taken and washed by saline for biochemical analysis. Other part of kidney tissue were kept in and stored at 10% formalin for histopathological studies.
Chemical analyses of plasma and kidney tissue homogenate were statistically analyzed to evaluate the effect of Zn-NPs through determination of urea and creatinine, antioxidant enzyme, malondialdehyde (MDA), interlukin 6 (IL-6), tumor necrosis factor α (TNF-α), carcinoembryonic antigen (CEA), nitric oxide (NO), -glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), Potassium (K) and total protein.
The biochemical assays in Fe-NTA treated group revealed:
• Renal toxicity showed by a significant increase in urea, creatinine and K levels and a significant decrease in total protein level in the plasma.
• Oxidative stress which was evidenced by a significant increase in MDA concentration in the plasma and in the kidney tissue accompanied with a significant decrease in the activities of CAT, SOD and GPx in the blood and in the kidney tissue.
• Also elevation of CEA level as tumor marker was also observed.
• Inflammation was reported by a significant increase in the level of cytokines in the plasma (IL-6 and TNF-ɑ), a significant increase in GGT activity and a significant increase in NO level.
• Histological examinations revealed severe damage in kidneys.
Oral administration of Zn-NPs pre i.p injection of Fe-NTA resulted in:
• Normalization of the plasma urea level and a significant decrease in creatinine level in the plasma.
• Normalization of MDA level in the plasma and in the kidney tissue by decreasing lipid peroxidation also, there are a significant increase in antioxidant enzyme activities CAT, SOD, GPx and GSH.
• Normalization of cytokines levels (TNF-ɑ and IL-6) in the plasma.
• Normalization of CEA level in the plasma which significantly decrease in compare to Fe-NTA.
• Normalization of NO level and GGT activity in the plasma in group treated with Zn-NPs as a chemo protective agent.
Treated animals with Zn-NPs alone showed insignificant changes in tested biochemical parameter in compare to normal control group. Concomitant with the improvement of the previous biomarkers histological finding in tissue of kidneys showed an ameliorative effect of Zn-NPs. According to the results obtained, it could be concluded that Zn-NPs might attenuate Fe-NTA induced oxidative organ injury and improve their enzymes activity. Therefore, Zn-NPs have an antioxidative potential and a protective effect against Fe-NTA induced damage in kidney.