Hyperoxaluria-induced tubular ischemia: the effects of verapamil and vitamin E on apoptotic changes with an emphasis on renal papilla in rat model

Abstract

An experimental study in rats was performed to evaluate the presence and the degree of both tubular apoptotic changes and crystallization at cortical, medullar and papillary regions of the kidney during hyperoxaluric phase and assess the possible protective effects of vitamin E and verapamil on these pathologic changes (particularly in papillary part of the affected kidneys). A total of 32 rats have been included into the study program. Hyperoxaluria was induced by continuous administration of ethylene glycol (0.75%). In addition to hyperoxaluria induction, animals in Groups 2 and 3 did receive a calcium channel-blocking agent (verapamil) and vitamin E, respectively. Histologic alterations of the kidneys including crystal formation together with apoptotic changes were evaluated on days 1, 14 and 28, respectively. Both apoptotic changes and the presence and degree of crystallization were assessed separately in renal cortical region, medulla and particularly papillary parts of the removed kidneys. Although verapamil did well limit the degree of crystal formation and apoptosis and brought it to the same levels observed in control group animals in all parts of the kidneys during intermediate phase, addition of vitamin E was failed to show the same protective effect during both intermediate and late phase evaluations. As demonstrated in our study, the limitation of both crystal deposition and apoptotic changes might be instituted by calcium channel-blocking agents. Clinical application of such agents in the prophylaxis of stone disease might limit the formation of urinary calculi, especially in recurrent stone formers.