Celecoxib offsets the negative renal influences of cyclosporine via modulation of the TGF-β1/IL-2/COX-2/endothelin ETB receptor cascade

Celecoxib, but not indomethacin, ameliorates the hypertensive and perivascular fibrotic actions of cyclosporine in rats: Role of endothelin signaling

“…Masson's trichrome staining was used for detection of periarterial renal fibrosis (Drury and Wallington, 1980;El-Gowelli et al, 2014).…”

“…The technique described in previous studies including ours (Chen and Sun, 2006;El-Mas et al, 2006;El-Gowelli et al, 2014) was employed for immunohistochemical determination of the protein expression of ET A and ET B receptors. Kidney sections (5 μm) were placed on positively charged adhesion microscope slides (Thermo Scientific®, Germany), deparaffinized in xylene and rehydrated in a series of decreasing ethanol concentration (100%, 95%, and 70%).…”

“…Each slide was counterstained with hematoxylin and dipped in ascending concentrations of alcohol and then xylene. The immunohistochemical signals of ET A and ET B receptors were quantified by Image J software (version 1.45s) together with computer-assisted microscopy, which was employed for this purpose using the greyscale thresholding as previously described (Kaczmarek et al, 2004;El-Gowelli et al, 2014). Briefly, the captured colored images were transformed into grey scale by changing image type from colored type into bit-8 type.…”

“…Two groups of rats (n = 6 each) were used and allocated to receive celecoxib (10 mg kg − 1 day − 1 ) (El-Gowelli et al, 2014) or CSA + celecoxib for 10 days. Because preliminary findings showed that CSA hypertension was abolished after concurrent administration of celecoxib, evidence was sought to implicate endothelin ET B receptors in the celecoxib effect.…”

“…The use of tacrolimus, another immunosuppressant with calcineurin inhibitory activity, and nonselective or cyclooxygenase-2 (COX-2) selective NSAIDs in salt-depleted rats impairs the glomerular filtration rate and reduces tacrolimus blood levels (Soubhia et al, 2005). By contrast, in a recent study we established evidence of a renoprotective effect for celecoxib, selective COX-2 inhibitor, against functional, inflammatory, and structural manifestations of CSA nephrotoxicity (El-Gowelli et al, 2014).…”