To investigate the protective effects of
eplerenone on
adriamycin-induced renal injury and the possible mechanisms involved, 36 male Sprague-Dawley rats were randomly divided into control group,
adriamycin nephropathy (AN) group and
eplerenone-treated group (100 mg·kg(-1)·d(-1) eplerenone). Blood pressure, 24-h urinary
protein, serum potassium,
sodium and
creatinine were measured 28 days after
adriamycin injection (a single tail
intravenous injection of 6.5 mg/kg
adriamycin). The morphological changes of renal tissues were observed by light and electron microscopy. Immunohistochemistry and Western blotting were performed to examine the expression of TGF-β(1) and
desmin in renal cortex. The results showed that 28 days after
adriamycin injection, there were no significant changes in the level of serum
potassium,
sodium,
creatinine concentrations and blood pressure values in the rats of the three groups. Meanwhile, the 24-h
proteinuria excretion in the AN group was significantly higher than that in the control group (P<0.01), but that in the
eplerenone-treated group was substantially reduced when compared with that in the AN group (P<0.05). Mild mesangial cell proliferation and matrix expansion, diffuse deformation and confluence of foot processes in podocytes were found in the AN group. By contrast, rats in the
eplerenone-treated group exhibited obvious attenuation of these morphological lesions. The
protein expression of TGF-β(1) and
desmin in the AN group was markedly up-regulated in contrast to that in the control group (P<0.01), whereas that in the
eplerenone-treated group was much lower than in the AN group (P<0.05). It was concluded that
eplerenone may ameliorate the
proteinuria and the development of pathological alteration in
adriamycin-induced nephropathy presumably via the inhibition of
cytokine release, and restore the morphology of podocytes independent of its blood pressure-lowing effects.