Abstract
Gentamicin (GM) is an antibiotic belonging to an aminoglycoside family that might induce nephrotoxicity in human and animal models via oxidative stress. Toll-like receptors (TLRs) are part of innate immune systems that participate in inflammatory responses. In this regard, we investigated the effect of GM on kidney functional and structural parameters, enzymatic antioxidant levels, and mRNA expression of TLR4 and IL6 in the rat kidney. Adult male Sprague Dawley rats were randomly divided into two groups (n = 10): Control and Gentamicin (100 mg/kg, i.p.). After ten days of GM administration, a blood sample was taken, and the kidneys were removed. The serum levels of creatinine (Cr) and blood urea nitrogen (BUN) were measured. Furthermore, the right kidney was preserved in formalin 10% for hematoxylin and eosin (H&E) staining, and the left kidney was kept at −80 °C for molecular and oxidative indexes analysis. Administration of GM caused tubular damages and functional disturbance. So that, Cr and BUN values in the GM group were higher than Control group. Furthermore, molecular findings showed upregulation of TLR4 and IL-6 mRNA expression in renal tissue of the GM-received group. In this study, superoxide dismutase (SOD) activity was slightly increased as a compensatory mechanism in response to elevated malondialdehyde (MDA) levels in the GM-treated group. On the other hand, the activity of catalase (CAT) and glutathione peroxidase (GPx) were significantly declined. Our results demonstrated that oxidative stress and subsequent TLR4 upregulation signaling pathways are involved in GM-induced nephrotoxicity.
Acknowledgments
The authors would like to thank the Research Consultation Center (RCC) of Shiraz University of Medical Sciences for their invaluable assistance in editing this article. In addition, the authors wish to thank Ms. Sheryl Thomas-Nikpoor, Language Editor, Springer Publications, for her valuable comments in editing this manuscript.
Author contributions
Z.K. and Z.P. designed the study. Z.P., S.J., and F.M. carried out the data acquisition. M.R., Z.K., and F.M. analyzed the data. Z.K. and M.R. interpreted the data. All authors contributed to the drafting of the manuscript and critically revised the manuscript for important intellectual content. All authors approved the final version of the manuscript.
Disclosure statement
The authors declare that there are no conflicts of interest.