Abstract
Previous studies have demonstrated that enalapril and verapamil seem to
attenuate the cyclosporine nephrotoxicity. However, the mechanisms have not been
completely understood, especially on molecular events. The aim of this study was
to examine the effect of individual or combined treatment on osteopontin,
TGF-β, endothelin-1 and procollagen alpha 1(I) mRNA expressions. Enalapril
(50 mg/L in drinking water) and verapamil (0.5 mg/kg/day, subcutaneously), alone
or in combination, were administered to rats with chronic cyclosporine
nephrotoxicity (cyclosporine, 25 mg/kg/day, subcutaneously) (n = 5 each). Five
rats treated with olive oil vehicle were used as control. After 4 weeks,
biochemical parameters were measured, and renal cortical mRNA levels were
evaluated by Northern blot analysis. Cyclosporine reduced renal creatinine
clearance significantly and induced renal cortical osteopontin, TGF-β,
endothelin-1 and procollagen alpha 1(I) gene expressions around 13.5 ± 1.3,
2.4 ± 0.2, 1.5 ± 0.1, 1.9 ± 0.1 folds, respectively. Individual treatment
with enalapril or verapamil significantly suppressed the osteopontin and
TGF-β mRNA expression, but not endothelin-1 and procollagen alpha 1(I).
Combined treatment also inhibited the osteopontin and TGF-βmRNA expression
but there was no difference between combined and individual treatment. In
conclusion, enalapril or verapamil significantly blunted the
cyclosporine-induced osteopontin and TGF-βgene expressions. However,
combined treatment did not show any additive effect.