Renoprotection with Pituitary Adenylate Cyclase-Activating Polypeptide in Cyclosporine A-Induced Nephrotoxicity

Abstract

Pituitary adenylate cyclase-activating polypeptide 38 ameliorated renal tubular injury, reduced oxidative injury, and inhibited the expression of TGF-β1 in CsA-exposed murine kidneys. Pituitary adenylate cyclase-activating polypeptide could be a novel renoprotective and antifibrotic agent for CsA nephrotoxicity.

The effects of pituitary adenylate cyclase activating polypeptide in renal ischemia/reperfusion

“…Apoptosis plays an important role in ischemia/reperfusion-induced kidney injury [40]. The antiapoptotic effect of PACAP in the kidney had already been proven in cisplatin-and in cyclosporin-induced kidney injury [21,28]. We found a significant decrease of the antiapoptotic Bcl-2 after renal ischemia/reperfusion, reversed by PACAP treatment [15].…”

“…furthermore, another study described that PACAP treatment reduced the severity of the histological alterations in diabetic kidneys and decreased the expression of several cytokines [5]. In cyclosporin A-induced kidney damage both in vivo and in vitro studies proved the protective effect of PACAP [21]. PACAP reduced TGF-β1 expression, the rise of LDHlevels, decreased apoptosis and the production of oxygen reactive species, suppressed the increased expression of the major extracellular matrix components, ameliorated the tubulointerstitial damage in the kidney and nearly normalized serum creatinine level [21].…”

“…In cyclosporin A-induced kidney damage both in vivo and in vitro studies proved the protective effect of PACAP [21]. PACAP reduced TGF-β1 expression, the rise of LDHlevels, decreased apoptosis and the production of oxygen reactive species, suppressed the increased expression of the major extracellular matrix components, ameliorated the tubulointerstitial damage in the kidney and nearly normalized serum creatinine level [21]. In cisplatin-induced kidney injury the administration of PACAP reduced the increased level of blood urea nitrogen and serum creatinine, decreased apoptosis and the severity of the renal morphological changes.…”

Pituitary adenylate cyclase-activating polypeptide prevents contrast-induced nephropathy in a novel mouse model

“…The overall magnitude of tubular damage was scored on the basis of the percentage of affected tubules by light microscopy in a high‐power field (five fields per animal) by investigators who were unaware of the treatment groups as described previously (Khan et al. ).…”

“…; Khan et al. ). We have, therefore, tested PACAP38 as a renoprotectant against contrast‐induced nephropathy using a novel preclinical mouse model.…”