Can spesific biomarkers be used to enlighten the major mechanisms of acute high dose diclofenac sodium-related nephrotoxicity?

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-kB], 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-kB 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 3 main steps (the hemodynamic-related 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.