Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

2018, vol. 27, nr 12, December, p. 1643–1650

doi: 10.17219/acem/75775

Publication type: original article

Language: English

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

Adalet Ozcicek1,A,B,D,F, Fatih Ozcicek1,B,E,F, Ferda Keskin Cimen2,C,F, Renad Mammadov3,B,F, Murat Cankaya4,C,F, Talat Ezmeci5,E,F, Durdu Altuner3,A,D,F

1 Department of Internal Medicine, Faculty of Medicine, Erzincan University, Turkey

2 Department of Pathology, Faculty of Medicine, Erzincan University, Turkey

3 Department of Pharmacology, Faculty of Medicine, Erzincan University, Turkey

4 Department of Biology, Arts and Sciences, Erzincan University, Turkey

5 Department of Public Health, Faculty of Medicine, Erzincan University, Turkey


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.
Conclusion. 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.

Key words

rats, cisplatin-nephrotoxicity, anakinra

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