Cyclosporine-A induced nephrotoxicity is associated with decreased renal bone morphogenetic protein-7 expression in rats.
The aim of our study was to investigate bone morphogenetic protein-7 (BMP-7) expression in a rat model of chronic cyclosporine (CsA) toxicity compare with healthy controls, as well as the influence of treatment with the angiotensin-converting enzyme inhibitor (ACEI) quinapril. Twenty-four male Wistar rats were divided into groups of eight animals treated with CsA (15 mg/kg intraperitoneally) for 8 weeks (CsA group) without or with quinapril (10 mg/kg per day in the drinking water: CsA group + Q) for comparison with healthy controls (H group). The renal tissues were examined by light microscopy for CsA toxicity; specifically, tubulointerstitial damage and afferent arteriolopathy as well as BMP-7 expression were semiquantitatively scored by immunohistochemical staining. Mean CsA levels were 1982 ng/mL and 1968 ng/mL for the CsA and CsA + Q groups, respectively. At the end of the study period, the mean serum creatinine levels were 0.8 +/- 0.2 mg/dL, 1.6 +/- 0.8 mg/dL, and 1.4 +/- 0.8 mg/dL for the H, CsA, and CsA + Q groups, respectively. Interstitial fibrosis, tubular atrophy, and afferent arteriolar hyalinization were present in the CsA group and, to a lesser degree, in the CsA + Q group, compared with the H group. CsA-treated rats displayed significantly decreased BMP-7 expression compared with healthy controls (P <.0005). BMP-7 expression was higher among the CsA + Q group than the the group CsA group. In a rat model histologic changes characteristic of CsA-induced nephrotoxicity are associated with decreased expression of BMP-7, which seems to be at least partially restored by ACE inhibition.
Tuğlular
S
S
Section of Nephrology, Marmara University Medical School, Istanbul, Turkey. serhantuglular@yahoo.com
Gogas Yavuz
D
D
Cakalağaoğlu
F
F
Citak
L
L
Arikan
H
H
Koçak
H
H
Ozener
C
C
Akoğlu
E
E
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000235:genetics* / Q000378:metabolism; D016572:Cyclosporine / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D007678:Kidney Glomerulus; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta; D016572:Cyclosporine