Zoledronic Acid Aggravates Kidney Damage During Ischemia Reperfusion Injury in Rat

Sehitoglu I., TÜMKAYA L., BEDİR R., Kalkan Y., Cure M. C., Yucel A. F., ...More

JOURNAL OF ENVIRONMENTAL PATHOLOGY TOXICOLOGY AND ONCOLOGY, vol.34, no.1, pp.53-61, 2015 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 34 Issue: 1
  • Publication Date: 2015
  • Doi Number: 10.1615/jenvironpatholtoxicoloncol.2015012424
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.53-61
  • Keywords: zoledronic acid, ischemia/reperfusion, kidney, interleukin-6, carbonic anhydrase II, CARBONIC-ANHYDRASE-II, BISPHOSPHONATES, INHIBITORS, CYTOKINES, GROWTH, POTENT, JAW
  • Recep Tayyip Erdoğan University Affiliated: Yes


Introduction: Zoledronic acid (ZA), a bisphosphonate, increases the levels of cytolcines, such as interleuldn-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), and reactive oxygen species (ROS) in subjects without cancer. Increased production of ROS, TNF-alpha, and IL-6 during ischemia and reperfusion (I/R) injury stimulates apoptosis that leads to renal injury. We aimed to investigate whether ZA treatment has a protective effect on renal tissues during I/R. Materials and Methods: Twenty-four Sprague-Dawley rats were used in this study, and they were subdivided randomly into three groups, each containing eight rats. Infrarenal abdominal aortic cross ligation was performed on the I/R group. After 2 h of ischemia, 2 h of reperfusion was applied. A single dose of 100 mu g/kg ZA was administered intraperitoneally to the ZA group. I/R was performed after 48 h. Results: Whereas TNF-alpha, IL-6, and nitric oxide (NO) levels of the I/R group were higher than those of the control group, TNF-a, IL-6, and NO levels of the ZA group were higher than those of the I/R group [TNF-alpha (p=0.038), IL-6 (p=0.012), NO (p=0.002), and caspase-3 (p=0.037)] and the control group [TNF-alpha (p<0.001), 11-6 (p<0.001), NO (p<0.001), and caspase-3 (p<0.001)]. Whereas the carbonic anhydrase II (CA-II) level of the ZA group was lower than that of the control group (p=0.040), the CA-II level of the I/R group was higher than that of the control group (p=0.020). Conclusion: ZA may aggravate renal injury during I/R by increasing cytokine production and apoptosis. It may also increase renal injury and metabolic acidosis during PR by suppressing CA-II enzyme activities.