The effect of anakinra to nephrotoxicity with cisplatin induced in rats: Biochemical, gene expression and histopathological evaluation

Abstract

Background. Oxidative stress and interleukin-1 beta (IL-1β) have been reported to play a role in the pathogenesis of nephrotoxicity induced by cisplatin. Objectives. The objective of this study was to investigate the effect of anakinra, which is an IL-1β receptor antagonist, on cisplatin-induced nephrotoxicity in rats, through biochemical, gene expression and histopathological analyses. Material and methods. The study was designed with 4 groups. For 1 week, the control group (C) and the cisplatin (Cis) group received distilled water, while the cisplatin + anakinra 50 (Cis + ANA50) group and the cisplatin + anakinra 100 (Cis + ANA100) group were intraperitoneally administered 50 mg/kg and 100 mg/kg of anakinra, respectively. The Cis, Cis + ANA50 and Cis + ANA100 groups were intraperitoneally injected with a 2.5 mg/kg dose of cisplatin for 7 days. After sacrifice, the kidney tissue of each rat was extracted for the assessment of the malondialdehyde (MDA) and total glutathione (tGSH) levels, and for gene expression analyses of IL-1β. The kidney tissues were histopathologically evaluated. Statistical analyses of the data were performed using one-way analysis of variance (ANOVA). Results. The administration of cisplatin (the Cis group) yielded a higher level of MDA (4.75 ±0.25 nmol/mL; p < 0.001) and lower levels of tGSH (1.80 ±0.35 mg/L; p < 0.001) compared to other groups. Cisplatin also increased IL-1β gene expression (6.33 ±0.27 gene expression levels; p < 0.001) compared to other groups. The impact of anakinra on the MDA and tGSH levels, and on IL-1β gene expression induced by cisplatin was observed as a reversal of these findings (p < 0.05). Anakinra better prevented an increase of the levels of MDA and IL-1β at a dose of 100 mg/kg compared to a 50 mg/kg dose. Conclusions. Anakinra prevents oxidative kidney damage induced by cisplatin in a dose-dependent manner. This result suggests that anakinra may be useful in the treatment of cisplatin-induced kidney damage.