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

Hyperoxaluria-induced tubular ischemia: the effects of verapamil and vitamin E on apoptotic changes with an emphasis on renal papilla in rat model
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DOI:
10.1007/s00240-011-0388-4
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发表时间:
2012-02-01
影响因子:
--
通讯作者:
Sarica, Kemal
Sarica, Kemal
中科院分区:
其他
文献类型:
--
作者:
Tanriverdi, Orhan;Telci, Dilek;Sarica, Kemal

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本实验观察了高尿酸血症大鼠肾皮质、髓质和乳头区肾小管凋亡和结晶的发生情况及程度,并探讨了维生素E和维拉帕米对这些病理变化(尤其是对病变肾乳头区)的保护作用。共32只大鼠纳入研究计划。通过连续给予乙二醇(0.75%)诱导高尿酸血症。除高尿酸诱导外,第2组和第3组动物分别接受钙通道阻滞剂(维拉帕米)和维生素E。分别在第1、14和28天评价肾脏的组织学改变,包括晶体形成和凋亡变化。分别在肾皮质区、髓质和特别是切除肾脏的乳头状部分中评估细胞凋亡变化以及结晶的存在和程度。虽然维拉帕米确实很好地限制了晶体形成和细胞凋亡的程度,并使其达到与对照组动物在中期肾脏所有部位观察到的相同水平,但在中期和晚期评价期间,添加维生素E未能显示出相同的保护作用。如我们的研究所示,晶体沉积和凋亡变化的限制可能是由钙通道阻滞剂引起的。临床应用此类药物预防结石病可能会限制尿路结石的形成,特别是在复发性结石患者中。
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.