الفهرس 
Acknowledgement
Ketoprofen administrationOnly 14 pages are availabe for public view
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Abstract
Our study was undertaken to evaluate the therapeutic effect of CurNPs againstKetoprofen induced nephrotoxicity in rats.For achievement of ourobjectives 60 adult male rats were obtained from a laboratory animal house,weighing about 180-200gms. The rats were randomly divided into four groups.
Ketoprofen administered group (First group) consisted of 15 male adult rats administrated Ketoprofen at a dose of 13.5 mg/kg for each rat by intramuscular injection. Five rats were randomly selected and sacrificed 2, 4 and 6 weeks post-dosing representing 3 different subgroups.
Ketoprofen and CurNPs treated group (Second group) consisted of 15 adult male rats were given Ketoprofen in the same dose and route as the first group. These rats were treated by CurNPs orally in a daily dose of 15 mg/kg for 6 successive weeks. Five rats were randomly selected and sacrificed 2, 4 and 6 weeks post-dosing representing 3 different subgroups.
Rats administered CurNPs only (Third group)consisted of 15 adult male rats were given CurNPs only in the same dose and route as the second group. Five rats were randomly selected and sacrificed 2, 4 and 6 weeks post-dosing representing 3 different subgroups.
Control untreated rats (Fourth group) consisted of 15 adult male rats administered only olive oil in a similar dose and route as Ketoprofen administered group. Five rats were randomly selected and sacrificed after 2, 4 and 6 weeks.
After sacrificing the rats, kidney tissues were fixed in neutral buffered formalin and subjected for histopathological examination, in addition to specific stains such as PAS stain and sirius red stain. Moreover, histopathological scoring was carried out for evaluation of all the microscopic lesions of the kidney for each group. Also, biochemical analysis of serum for detection of kidney function parameters (urea and creatinine) and oxidative stress indices (MDA and TAC) in all experimental groups were carried out.
Histopathological examination of H&E stained tissue sections from the kidneys of rats sacrificed 2 weeks post-Ketoprofen administration showed glomerular changesexpressed by an expanded mesangial matrix with thickening of the glomerular basement membrane and congestion of the glomerular capillary tuftswere seen in all examined rats. There wasmild vacuolar degeneration of renal tubules predominated in all 5 examined rats also, haemoglobinic nephrosis and apoptosisof the renal tubules were found in 2 rats out of 5 rats. Moreover the angiopathic changes of the blood vessels exhibited in all rats. The medullary tubules exhibited focal areas of intraluminal pale eosinophilic proteinaceous materialin all examined rats.
Regarding rats sacrificed after 4 weeks post Ketoprofen administration, in addition to the lesions mentioned after 2 weeks, rats in this subgroup showed focal segmental glomerulosclerosisconfirmed by PAS stain, in 3 rats out of 5 rats.Focal global glomerulosclerosis demonstrated by sirius red stain in 3 rats out of 5 rats. The prominent form of cortical lesions in this subgroup was epithelial cast formation also, focal areas of toxic tubular necrosis of some renal tubulesthat wereseen in all 5 examined rats.The same angiopathic changes resemble those of the first subgroup after 2 weeks were seen in all 5 examined rats . In 2 rats out of 5 rats,focal dystrophic calcification and cystic dilation of renal medullary tubules were also seen as advanced lesions in this subgroup.
Histopathological examination of rats sacrificed 6 weeks post-Ketoprofen administration revealedmore progressive alterations.Beside the glomerular lesions mentioned previously in the first subgroup after 2 weeks, focal segmental glomerulosclerosisand focal global glomerulosclerosiswere found in 3 rats out of 5 rats. The most characteristic glomerular distortion in this subgroup was Bowman’s capsule metaplasiaaffecting 3 rats out of 5 rats.Intratubular RBCs castswere a distinctive feature of some cortical tubules, predominated in all examined.
Some blood vessels showed mixed thrombus.The medullary tubules showedred blood cells cast admixed with WBCsaccompanied with peritubular fibrosisexhibited in 3 rats out of 5 rats.
In the treated group rats sacrificed 2 weeks post-Ketoprofen and CurNPs administration revealed glomerular alterationsas previously described in the Ketoprofen administered group after 2 weeks. There was amelioration in the tubular lesions, observed in some renal tubuleswith granular degenerationdemonstrated in 1 rat out of 5 rats. The medulla showedfocal areas of intraluminal pale eosinophilic proteinaceous materialin all 5 examined rats.
Rats sacrificed 4 weeks post Ketoprofen and CurNPs administration exhibited slight improvement in the glomerular lesions. However, congestion in glomerular capillary tufts, as well as a complete obliteration of Bowman’s spacewas found in 4 rats out of 5 rats.The tubular changes were expressed by mild vacuolar degeneration and epithelial cast formation,which seen in all rats. The medulla showed the interstitial cellular reaction of mononuclear inflammatory cellsin 2 rats out of 5 rats.
Rats sacrificed 6 weeks post-Ketoprofen and CurNPs administrationrevealed amelioration in all lesions expressed by mild glomerular alterations and mild granular degeneration of renal tubular epitheliumthat appeared in 4 rats out of 5 rats.Mild angiopathic changeswere observed in 2 rats out of 5 rats.Mild sloughing in the renal epithelium of some medullary tubuleswas seen in 4 rats out of 5 rats.
CurNPs only treated group and control rats exhibited normal architecture of both cortex and medulla.
Concerning the histopathological scoring, after 2 weeks there was a significant improvement in the tubular lesions in Ketoprofen and CurNPs treated group when compared with Ketoprofen administered group, however, after 4 weeks, significant improvement in glomerular and tubular lesions in Ketoprofen and CurNPs treated group was found when compared with Ketoprofen administered group.
Moreover, after 6 weeks there was significant improvement in each glomerular, tubular and interstitial lesions.
Serum biochemical analysis of urea levels after 2, 4 and 6 weeks showed significant improvement in the Ketoprofen and CurNPs treated group when compared with the Ketoprofen administered group. The serum level of creatinine after 2 and 6 weeks exhibited significant improvement in the Ketoprofen and CurNPs treated group when compared with Ketoprofen administered group but after 4 weeks there was a numerically decrease in creatinine levelsin the Ketoprofen and CurNPs treated group in comparison withthe Ketoprofen administered group.
Significant improvement was observed in the serum level of MDA in Ketoprofen and CurNPs treated group as compared with the Ketoprofenadministered group after 2,4 and 6 weeks.The serum level of TAC in the Ketoprofen and CurNPs treated group showed a numerical increase as compared with the Ketoprofen administered group after 2,4 and 6 weeks.