A novel approach to contrast-induced nephrotoxicity: The melatonergic agent agomelatine

Abstract

Objective: To study the potential nephroprotective role of agomelatine in rat renal tissue in cases of contrast-induced nephrotoxicity (CIN). The drug's action on the antioxidant system and proinflammatory cytokines, superoxide dismutase (SOD) activity, levels of glutathione (GSH) and malondialdehyde (MDA) and the gene expression of interleukin-6 (IL-6), tumour necrosis factor (TNF)-alpha and nuclear factor kappa B (NF-kappa B) was measured. Tubular necrosis and hyaline and haemorrhagic casts were also histopathologically evaluated. Methods: The institutional ethics and local animal care committees approved the study. Eight groups of six rats were put on the following drug regimens: Group 1: healthy controls, Group 2: GLY (glycerol), Group 3: CM (contrast media-iohexol 10 ml kg(-1)), Group 4: GLY+CM, Group 5: CM+AGO20 (agomelatine 20 mg kg(-1)), Group 6: GLY+CM1AGO20, Group 7: CM1AGO40 (agomelatine 40 mg kg(-1)) and Group 8: GLY+CM+AGO40. The groups were evaluated by one-way analysis of variance and Duncan's multiple comparison test. Results: Agomelatine administration significantly improved the serum levels of blood urea nitrogen (BUN) and creatinine, SOD activity, GSH and MDA. The use of agomelatine had substantial downregulatory consequences on TNF-alpha, NF-kappa B and IL-6 messenger RNA levels. Mild-to-severe hyaline and haemorrhagic casts and tubular necrosis were observed in all groups, except in the healthy group. The histopathological scores were better in the agomelatine treatment groups. Conclusion: Agomelatine has nephroprotective effects against CIN in rats. This effect can be attributed to its properties of reducing oxidative stress and inhibiting the secretion of proinflammatory cytokines (NF-kappa B, TNF-alpha and IL-6). Advances in knowledge: CIN is one of the most important adverse effects of radiological procedures. Renal failure, diabetes, malignancy, old age and nonsteroidal anti-inflammatory drug use pose the risk of CIN in patients. Several clinical studies have investigated ways to avoid CIN. Theophylline/aminophylline, statins, ascorbic acid and iloprost have been suggested for this purpose. Agomelatine is one of the melatonin ligands and is used for affective disorders and has antioxidant features. In this study, we hypothesized that agomelatine could have nephroprotective, antioxidant and anti-inflammatory effects against CIN in rats.