Heresh Rezaei - Pharmaceutical Sciences Research Center, Shiraz University Of Medical Sciences, Shiraz, Iran
Ayeh Rouhani - Pharmaceutical Sciences Research Center, Shiraz University Of Medical Sciences, Shiraz, Iran
Jale Yüzügülen - Eastern Mediterranean University, Faculty of Pharmacy, Famagusta, North Cyprus, Turkey
Fatemeh Ghaderi - Pharmaceutical Sciences Research Center, Shiraz University Of Medical Sciences, Shiraz, Iran
Rahil Fazlinezhad - Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Mohammad Reza Kiafar - Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Zahra Honarpishefard - Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Pargol Matinpour - Eastern Mediterranean University, Faculty of Pharmacy, Famagusta, North Cyprus, Turkey
Abdollah Arjmand - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Negar Azarpira - Transplant Research Center, Shiraz University of Medical Sciences
Seyed Mohammad Amin Kashani - Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Forouzan Khodaei - Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Akram Jamshidzadeh - Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Reza Heidari - Shiraz University of Medical Sciences, Pharmaceutical Sciences Research Center

Zoledronic acid (ZLD) is a bisphosphonate drug widely administered against pathological conditions such as hypercalcemia of malignancy, osteoporosis, bone metastases from solid tumors, and multiple myeloma. Unfortunately, renal injury is a serious and dose-limiting adverse effect of ZLD. There is no specific mechanism for ZLD-induced renal damage. The current study aimed to assess the effects of ZLD (۱۰ and ۱۵ mg/kg, i.p., single dose) on the kidneys of drug-treated rats. In this regard, several parameters were assessed, including oxidative stress biomarkers, serum level of BUN and creatinine, inflammatory cytokines, kidney histopathology, and indices of mitochondrial function. A significant increase in serum Cr and BUN revealed renal injury. Moreover, kidney histopathological changes, including interstitial inflammation, tissue necrosis, and tubular atrophy, were detected in ZLD-treated rats. Biomarkers of oxidative stress, including a significant increase in reactive oxygen species (ROS), depletion of kidney glutathione (GSH) stores, increased lipid peroxidation, and suppression of the total antioxidant capacity, were detected in ZLD-treated animals. ZLD also significantly increased renal levels of TNF-α, IL-۶, and IL-۱β. ZLD exposure was also associated with significantly decreased mitochondrial dehydrogenases activity, mitochondrial depolarization, mitochondrial permeabilization, and ATP depletion. These data highlight mitochondrial dysfunction, inflammatory response, and oxidative stress as potential mechanisms in ZLD-induced kidney injury.

Bisphosphonates, drug safety, Mitochondrial dysfunction, Kidney Injury, Renal Failure, pharmacotherapy