The role of vitamin E in the prevention of zoledronic acid-induced nephrotoxicity in rats: a light and electron microscopy study

Abstract

IntroductionBisphosphonates are widely used in metastatic cancer such as prostate and breast cancer, and their nephrotoxic effects have been established previously. In this study we aimed to evaluate both the nephrotoxic effects of zoledronic acid (ZA) and the protective effects of vitamin E (Vit-E) on this process under light and electron microscopy.Material and methodsA total of 30 male Sprague-Dawley rats were divided into 3 groups. The first group constituted the control group. The second group was given i.v. ZA of 3 mg/kg once every 3 weeks for 12 weeks from the tail vein. The third group received the same dosage of ZA with an additional i.m. injection of 15 mg Vit-E every week for 12 weeks. Tissues were taken 4 days after the last dose of ZA for histopathological and ultrastructural evaluation. Paller score, tubular epithelial thickness and basal membrane thickness were calculated for each group.ResultsFor group 2, the p-values are all < 0.001 for Paller score, epitelial thickness, and basal membrane thickness. For group 3 (ZA + Vit. E), the p-values are < 0.001 for Paller score, 0.996 for epitelial thickness, and < 0.001 basal membrane thickness. Significant differences were also observed in ultrastructural changes for group 2. However, adding Vit-E to ZA administration reversed all the histopathological changes to some degree, with statistical significance.ConclusionsAdministration of ZA had nephrotoxic effects on rat kidney observed under both light and electron microscopy. Concomitant administration of Vit-E significantly reduces toxic histopathological effects of ZA.

Zoledronic acid‐induced oxidative damage and endoplasmic reticulum stress‐mediated apoptosis in human embryonic kidney (HEK‐293) cells

“…Apoptosis induction may contribute to the pathophysiology of focal segmental glomerulosclerosis by bisphosphonates. [ 69 ] Also, it has been shown that zoledronic acid causes renal tubular cell death by apoptosis. [ 69 ] Similarly, the results of our study showed concentration‐dependent apoptosis induction.…”

Zoledronic Acid-Induced Acute Renal Failure in Multiple Myeloma

“…Conversely, in the experimental animal study, 100% of rats presented histological renal lesions after intravenous bisphosphonate therapy [10]. These lesions were basal membrane thickness, cytoplasmic vacuolization, loss of brush border, tubular epithelial smoothness, tubular lumen obstruction and cell necrosis [10].…”

“…The mechanisms evoked for this nephrotoxicity are: the aggregation of bisphosphonates and calcium complexes in renal cells, and even more the induction by bisphosphonates of renal tubular cell death (similar to their apoptotic effect on osteoclasts) [10]. This is particularly due to the renal uptake and elimination of bisphosphonates [15].…”

“…Concomitant administration of vitamin E (15mg/week intramuscularly) significantly reduces the nephrotoxicity of ZA as demonstrated by the experimental animal study of Serti IU et al [10].…”

Protective effect of estradiol copreservation against kidney ischemia‐reperfusion injury

“…Paller score was used to describe histological changes 12 . Ten kidney tubules were randomly chosen under one vision to evaluate the histological score.…”