الفهرس 
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Abstract
Medicines are required for humans to cure diseases but at the same time, they are foreign objects to the body. Hence, the human body tries to excrete them. It is highly desirable that the medicines get eliminated from the human body immediately after showing their drug action. The longer time the drug spends in the body, the greater are its side effects. The human body has a natural mechanism to eliminate these foreign objects (medicines). This is mainly facilitated by the process known as drug metabolism
Amifostine may be the most promising cytoprotector for the kidney. Amifostine is a thio phosphate cytoprotective agent developed as a radio protector. Also it is used to reduce the side effects associated with platinum-containing agents. However, approximately 90% of amifostine was rapidly cleared from plasma after 6 minutes after intravenousadministration.
The efficacy of amifostine use for alleviating the side effects of chemotherapy and space travel is limited by the extremely short half-life. The current study describes the preparation and characterization of compartmentalized hollow silica nanospheres encapsulated with amifostine as a model for drug delivery domains. The synthesized nanoemulsion of hollow structured porous silica and silica encapsulated with amifostine was extensively characterized to determine the hydrodynamic size, particle shape via TEM and DLS techniques. The ultimate objective of the other nano delivery system was to alter the normal biofate of potent drug molecules in the body following their intravenous administration to markedly improve their efficacy and reduce their potential intrinsic severe adverse effects. Furthermore this study aimed to elucidate the ameliorative effect of amifostine silica nanoparticles SiNPs@AMF against nephrotoxicity
50 rats were randomly divided into five equal groups (10 rats each):
- Normal Control (NC) group: Injected with saline daily for one month.
- Silica Nanoemlusion (SiNPs) group: Injected with particles of silicananoemulsion (SiNPs) in a dose of 150 mg/kg/day for one month.
- Silica nanoemulsion of amifostine (SiNPs@AMF) group: Injected with particles of silica nanoemulsion of amifostine (SiNPs@AMF) in a dose of 150 mg/kg/day for one month.
- Cisplatin (Cis) group: Injected twice with cisplatin in a dose of 20 mg/kg body weight (day after day) to induce renal toxicity.
- Silica nanoemulsion of amifostine + cis (SiNPs@AMF+Cis) group: Injected (i.p.) with particles of silica nanoemulsion of amifostine (SiNPs@AMF) in dose of 150 mg/kg/day for 3 weeks then injected with two doses of cisplatin (20 mg/kg.) day after day followed by amifostine injection (SiNPs@AMF) to complete one month.
At the end of the experimental period urine was collected before the end of experiment by 24 hours in aseptic tubes and centrifuged for 20 minutes at 2000 -3000 rpm. The supernatant was collected for biochemical analysis of creatinine and 8 hydroxy 2 deoxy guanosine. Blood was withdrawn from the retro-orbital venous plexus of the eye using a heparinized capillary tube, under light anesthesia by diethyl ether, blood was collected in tubes for biochemical analysis of (RANTS, Osteopontin, KIM-1,TIMP-1, HA , MMP-9, MCP-1, Urea and Creatinine )
Kidneys were removed quickly and placed on ice cold saline, perfused with the same solution to remove blood cells then left kidney was put in formalin saline mixture for histopathological examination and immune histochemistry. The right kidney was blotted on filter paper and frozen at -80oC.The frozen tissues were cut into small pieces for molecular examination of miRNA 29 a, miRNA193a, nephrin mRNA and Podocin mRNA. Tissue homogenate used for estimation of nitric oxide, malondialdhyde, paraoxinase.
The results obtained indicated that injection of cisplatin to rats with dose 20 mg/kg resulted in:
• Elevation in kidney function parameters
• Elevation in kidney nitric oxide and malondialdhyde
• Elevation in urinary 8 OHdG and serum homocystein.
• Elevation RANTS, osteopontin, KIM-1 and TIMP-1.
• Elevation in serum HA, MMP-9, NF-κB and MCP-1.
• Elevation in expression level of miRNA 193a.
• Decrease in expression levels of nephrin mRNA, podocin mRNA and mi RNA 29 a.
Protection by nanoemulisifed amifostine has attenuated all the damage exerted by cisplatin.
Conclusion
cisplatin induced nephrotoxicity in tested male albino rats manifested by changes in urinary 8 hydroxy 2 deoxyguanosine (8OHdG) serum homocysteine (Hcy), RANTS, osteopontin (OPN), kidney injury molecule -1 (KIM-1), tissue inhibitor metalloproteinase-1 (TIMP-1), hyaluronic acid (HA) matrix metalloproteinase -9 (MMP-9), necrosis factor kappa B(NF-κB) and monocyte chemoattracted protein (MCP-1) levels show a significant elevation in Cisplatin group in comparison with NC group and down regulation of the expression of nephrin mRNA, podocin mRNA and miRNA 29a strongly in nephrotoxic group. Nephrotoxic animals protected with a mifostine nano emulsion recorded a less significant increase in 8OHdG, Hcy, RANTS, OPN, KIM-1, TIMP-1, HA, MMP-9, NF-κB and MCP-1 levels with enhancement of expression of nephrin mRNA and podocin mRNA compared to NC. Contrarily, these disturbances were augmented by protection of (SiNPs@AMF) injection. The obtained results are considered as potential implications that offer a new approach in attenuating drug induced nephrotoxicity.
Recommandation
Regarding the rapid increase in incidence of nephrotoxicity around the world as aresult of drug utilization, it is important to consider the possible use of nanoemulsifiedamifostine to attenuate the nephrotoxicity which might focus the light on its protective prevention strategy against cisplatin nephrotoxicity based on the experimental findings.