Can Spesific Biomarkers Be Used to Enlighten the Major Mechanisms of Acute High Dose Diclofenac Sodium-Related Nephrotoxicity?

Abstract

Aim: The aim of this study was to examine the basic mechanisms that play a role in the acute nephrotoxicity caused by diclofenac sodium. Materials and Methods: Only water was given to the control group; however, the diclofenac sodium group was group intoxicated by giving water-soluble, 240 mg/kg, oral single dose diclofenac sodium. After 24 hours, all animals were sacrificed and histopathological analyzes were performed. The levels of spesific biomarkers [vascular endothelial growth factor (VEGF), nuclear factor-kappa B (NF-kappa B), matrix metalloproteinase-9 (MMP-9), metalloproteinase tissue inhibitor-1 (TIMP-1) and carcinoembryonic antigen (CEA)] that may be related to the nephrotoxicity mechanism were evaluated. Results: As a result of biochemical analysis, we found that VEGF, TIMP-1, NF-kappa B and CEA levels were significantly higher and MMP-9 levels were significantly lower in diclofenac sodium group compared to control group. Nephrotoxicity related histopathological changes were observed in the sections of diclofenac sodium group. Conclusion: This study has shown that the biomarkers we evaluated in the diclofenac sodium-induced acute high-dose intoxication model we created can help us to identify the nephrotoxicity and to explain the nephrotoxicity mechanism with the three main steps (the hemodynamicrelated pathway, the inflammation-related pathway, and the oxidative stress-related pathway). With a simple version of this panel adapted to emergency departments, we may be able to diagnose diclofenac sodium-related nephrotoxicity.