Zoledronic acid aggravates kidney damage during ischemia reperfusion injury in rat.
BACKGROUND
Zoledronic acid (ZA), a bisphosphonate, increases the levels of cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α), and reactive oxygen species (ROS) in subjects without cancer. Increased production of ROS, TNF-α, 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.


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 µg/kg ZA was administered intraperitoneally to the ZA group. I/R was performed after 48 h.


RESULTS
Whereas TNF-α, IL-6, and nitric oxide (NO) levels of the I/R group were higher than those of the control group, TNF-α, IL-6, and NO levels of the ZA group were higher than those of the I/R group [TNF-α (p=0.038), IL-6 (p=0.012), NO (p=0.002), and caspase-3 (p=0.037)] and the control group [TNF-α (p<0.001), IL-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).


CONCLUSIONS
ZA may aggravate renal injury during I/R by increasing cytokine production and apoptosis. It may also increase renal injury and metabolic acidosis during I/R by suppressing CA-II enzyme activities.
Department of Pathology, Faculty of Medicine, RecepTayyip Erdogan University, Rize, Turkey.
Ibrahim
I
Sehitoglu
Department of Histology and Embryology, Faculty of Medicine, RecepTayyip Erdogan University, Rize, Turkey.
Levent
L
Tumkaya
Department of Pathology, Faculty of Medicine, RecepTayyip Erdogan University, Rize, Turkey.
Recep
R
Bedir
Department of Histology and Embryology, Faculty of Medicine, RecepTayyip Erdogan University, Rize, Turkey.
Yildiray
Y
Kalkan
Department of Biochemistry, Faculty of Medicine, RecepTayyip Erdogan University, Rize, Turkey.
Medine Cumhur
MC
Cure
Department of Surgery, Faculty of Medicine, RecepTayyip Erdogan University, Rize, Turkey.
Ahmet Fikret
AF
Yucel
Department of Urology, Faculty of Medicine, RecepTayyip Erdogan University, Rize, Turkey.
Orhan Unal
OU
Zorba
Internal Medicine, Kumru State Hospital, Ordu, Turkey.
Suleyman
S
Yuce
Department of Internal Medicine, Faculty of Medicine, RecepTayyip Erdogan University, Rize, Turkey.
Erkan
E
Cure
D000818:Animals; D050071:Bone Density Conservation Agents / Q000633:toxicity*; D024402:Carbonic Anhydrase II / Q000032:analysis / Q000037:antagonists & inhibitors; D004164:Diphosphonates / Q000633:toxicity*; D007093:Imidazoles / Q000633:toxicity*; D015850:Interleukin-6 / Q000032:analysis; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009569:Nitric Oxide / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D000077211:Zoledronic Acid
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D000077211:Zoledronic Acid; D024402:Carbonic Anhydrase II