Effects of mycophenolate mofetil and lisinopril on collagen deposition in unilateral ureteral obstruction in rats.

BACKGROUND/AIMS: 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.

CONCLUSION

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.