Hyperoxaluria-induced tubular ischemia: the effect of verapamil on the limitation of tissue HIF-1 alpha levels in renal parenchyma

Abstract

The effect of verapamil on tubular ischemia that is demonstrated by HIF-1alpha positivity in tubular cells following hyperoxaluria was evaluated in a rabbit model. Thirty-six healthy male rabbits were randomly divided into three groups. Animals in the hyperoxaluric group were fed with 0.75% ethylene glycol. The verapamil group was fed identically to the hyperoxaluric group. Additionally, the verapamil group received verapamil orally (0.1 mg/kg). The control group received no special diet. Six animals in each group were killed on the 7th day of the experiment and the remaining six at the 28th day. Kidneys of the rabbits were examined by histopathologic and immunohistochemical analysis to detect the presence and degree of HIF-1alpha positivity. On the 7th day analysis, severe and moderate degree staining for HIF-1alpha in hyperoxaluric group were shown in four and two, respectively. In the verapamil group, however, three of six specimens showed nuclear staining (moderate in two and severe in one). Two of six specimens in the control group had minimal staining. The 28th day evaluation showed that two of the hyperoxaluric group had minimal degree nuclear staining but not in the remaining four. No staining was shown in the verapamil and control group animals. Hyperoxaluria-related ischemia formation may be responsible for subsequent alterations in renal tubules. As a protective agent, verapamil was found to limit the presence of hypoxic changes as documented by HIF-1 alpha positivity in this study. These data also support the presence ischemic insult after hyperoxaluria induction in animal model.