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Evaluation of the protective effect of edaravone on doxorubicin nephrotoxicity by [99mTc]DMSA renal scintigraphy and biochemical methods

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Abstract

To evaluate the nephroprotective effect of edaravone on doxorubicin-induced nephrotoxicity. In this experimental study, twenty-eight Wistar male rats were used. The rats were separated into 4 groups (n = 7); group І (control), rats were treated with saline (4 ml/kg) and group ІІ (doxorubicin), nephrotoxicity was induced by three doses of 18 mg/kg/i.p. doxorubicin, at a 24-h interval on the 12th, 13th, and 14th days. Group ІІІ (edaravone), rats were treated with edaravone (30 mg/kg/for 14 days), and group ІV (edaravone + doxorubicin), rats were treated with edaravone (30 mg/kg/for 14 days) and doxorubicin were injected (18 mg/kg/for 3 days; at a 24-h interval on the 12th, 13th, and 14th days). On the 15th day of the experiment, technetium-99m-labeled dimercaptosuccinic acid ([99mTc]DMSA) uptake was obtained in both kidneys and biochemical parameters from serum and kidney tissue were measured. Doxorubicin led to nephrotoxicity through elevation of serum blood urea nitrogen (BUN), creatinine and tumor necrosis factor-α (TNF-α), nitric oxide (NO), and interleukin-6 (IL-6) in kidney tissue and decreased [99mTc]DMSA uptake level in the kidney when compared with control group (p < 0.01). Pretreatment edaravone significantly decreased BUN and creatinine, also kidney tissue TNF-α, IL-6, NO, and increased [99mTc]DMSA uptake level compared with the doxorubicin. Edaravone has a significant nephroprotective effect through the attenuation of oxidative stress and inflammatory markers during doxorubicin-induced nephrotoxicity in rats.

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Authors and Affiliations

  1. Department of Nuclear Medicine, Faculty of Medicine, Tokat Gaziosmanpasa University, Tokat, Turkey

    Fadime Demir

  2. Department of Nephrology, Faculty of Medicine, Firat University, Elazig, Turkey

    Mustafa Demir

  3. Department of Physiology, Faculty of Medicine, Tokat Gaziosmanpasa University, Tokat, Turkey

    Hatice Aygun

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  1. Fadime Demir
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  2. Mustafa Demir
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  3. Hatice Aygun
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HA: research concept and design. HA, FD, MD: conducting experiments, data collecting, analysis, and interpretation of data. HA: Preparation of articles and revisions. All authors read and approved the final version of the manuscript.

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Correspondence to Hatice Aygun.

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Demir, F., Demir, M. & Aygun, H. Evaluation of the protective effect of edaravone on doxorubicin nephrotoxicity by [99mTc]DMSA renal scintigraphy and biochemical methods. Naunyn-Schmiedeberg's Arch Pharmacol 393, 1383–1390 (2020). https://doi.org/10.1007/s00210-020-01832-2

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