Effects of mycophenolate mofetil and lisinopril on collagen deposition in unilateral ureteral obstruction in rats.
OBJECTIVE
Unilateral ureteral obstruction (UUO) in rats has been used as a model of renal interstitial fibrosis, in which therapeutic trials can be of important clinical relevance. In this study, we investigated the effects of mycophenolate mofetil (MMF), the angiotensin-converting enzyme (ACE) inhibitor lisinopril (L), and the combination of both drugs, given daily for 14 days to UUO rats, on the renal fibrogenic process triggered by UUO.


METHODS
Rats underwent surgical UUO, followed by treatment with daily doses of either MMF, lisinopril, or both, and were then sacrificed after 14 days. Kidney fragments were fixed for histopathological examination (hematoxylin-eosin and periodic acid-Schiff reactive) and immunohistochemistry for myofibroblasts (alpha-smooth muscle actin; alpha-SMA) and macrophages (ED-1). Histomorphometrical analysis of collagen was performed with Sirius red staining, and collagen content was assessed by the amount of hydroxyproline. Cortex and medulla were analyzed separately.


RESULTS
MMF, lisinopril and MMF+L reduced the density of alpha-SMA- and ED-1-positive cells (p < 0.05), interstitial volume (p < 0.05) and decreased Sirius-red-stained areas by 54.6, 35.6 and 58.0%, and hydroxyproline content by 60.1, 49.7 and 62.7%, respectively. No differences were observed among treated groups.


CONCLUSIONS
MMF and the ACE inhibitor lisinopril attenuated the progression of the fibrogenic process of UUO in an equivalent manner. The combination of both drugs did not add any further improvement in the collagen content.
Gonçalves
Rômulo G
RG
Serviço de Nefrologia, Departamento de Clínica Médica, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil.
Biato
Marco A
MA
Colosimo
Ricardo D G
RD
Martinusso
Cesônia A
CA
Pecly
Inah D
ID
Farias
Eliene K
EK
Cardoso
Lúcio R
LR
Takiya
Christina M
CM
Ornellas
José F R
JF
Leite
Maurilo
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D003094:Collagen / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D017706:Lisinopril / Q000494:pharmacology*; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014517:Ureteral Obstruction / Q000378:metabolism*
D000806:Angiotensin-Converting Enzyme Inhibitors; D003094:Collagen; D017706:Lisinopril; D009173:Mycophenolic Acid