High dose zoledronic acid increases ischemia-reperfusion damage of the liver

I. Aydin, I. Sehitoglu, E. Ozer, Y. Kalkan, L. Tumkaya, M.C. Cure, E. Cure

Department of General Surgery, Health Science University, Fatih Sultan Mehmet Training and Research Hospital, Istanbul, Turkey. ibrahimaydin061@gmail.com

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• Pharmacology

OBJECTIVE: Zoledronic acid (ZA), a nitrogen-containing bisphosphonate, has been reported to exhibit a protective effect against cancers and prevent bone fractures. It also induces apoptosis by increasing proinflammatory cytokines and oxidative stress. Oxidative stress increases significantly during ischemia-reperfusion (IR) injury. The liver is highly sensitive to IR injury. In this study, we aim to investigate whether high-dose ZA treatment affects the liver during IR.

MATERIALS AND METHODS: We used twenty-one Sprague-Dawley male rats in our study, and they were subdivided randomly into three groups, each containing seven rats. A single dose of 100 μg/kg ZA was administered via the intraperitoneal route in the ZA group. Forty-eight hours after the ZA administration, infrarenal abdominal aortic cross ligation was performed on the ZA and IR groups. After 2 hours of ischemia, 2 hours of reperfusion was applied.

RESULTS: The malondialdehyde (MDA) level of the control group was significantly lower than the IR (p = 0.006) and ZA (p<0.001) groups. However, the superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) values of the control group were significantly higher than the values of the IR group (p<0.05, p<0.001, and p<0.05) and ZA group (p = 0.002, p<0.001, and p<0.001). Caspase-3 activity was significantly higher in the IR group as compared to the control group (p<0.001). The caspase-3 activity in the ZA group, on the other hand, was higher than both the control (p<0.001) and IR groups (p<0.001).

CONCLUSIONS: High-dose ZA may exacerbate liver injury during IR by increasing reactive oxygen species production and apoptosis.

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