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Effect of a recombinant manganese superoxide dismutase on prevention of contrast-induced acute kidney injury

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Abstract

Background

Contrast media (CM)-induced nephropathy (CIN) is an acute deterioration of renal function following administration of CM mediated to a large extent by the increased production of ROS within the kidney. Aim of this study was to evaluate whether a novel isoform of a recombinant Manganese SOD (rMnSOD) could provide an effective protection against CIN; this molecule shares the same ability of physiological SODs in scavenging reactive oxygen species (ROS) but, due to its peculiar properties, enters inside the cells after its administration.

Methods

We studied the effects rMnSOD on oxidative damage in a rat model of CIN in uninephrectomized rats, that were randomly assigned to 3 experimental Groups: Group CON, control rats treated with the vehicle of CM, Group HCM, rats treated with CM and Group SOD, rats treated with CM and rMnSOD.

Results

In normal rats, pretreatment with rMnSOD, reduced renal superoxide anion production, induced by the activation of NAPDH oxidase, by 84 % (p < 0.001). In rats of Group HCM, ROS production was almost doubled compared to rat of Group CON (p < 0.01) but returned to normal values in rats of Group SOD, where a significant increase of SOD activity was detected (+16 % vs HCM, p < 0.05). Administration of CM determined a striking fall of GFR in rats of Group HCM (−70 %, p < 0.001 vs CON), greatly blunted in Group SOD (−28 % vs CON, p < 0.01); this was associated with a lower presence of both tubular necrosis and intratubular casts in SOD-treated rats (both p < 0.01 vs Group HCM).

Conclusions

Our data indicate that rMnSOD is able to reduce renal oxidative stress, thus preventing the reduction of GFR and the renal histologic damage that follows CM administration.

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Abbreviations

b.w.:

Body weight

CIN:

Contrast media-induced nephropathy

CM:

Contrast media

DCF:

Dichlorofluorescein

DCFH-DA:

2′,7′-Dichlorofluorescin diacetate

GFR:

Glomerular filtration rate

IF:

Intensity Fluorescence

i.p.:

Intraperitoneal

i.v.:

Intravenous

LSA:

Liposarcoma cell line

rMnSOD:

Recombinant manganese superoxide dismutase

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

WST:

Water-soluble tetrazolium salt

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Conflict of interest

None of the authors have anything to disclose.

Author information

Authors and Affiliations

  1. Department of Nephrology, University Federico II of Naples, 80131, Naples, Italy

    Antonio Pisani, Massimo Sabbatini, Eleonora Riccio & Roberta Rossano

  2. Department of Nephrology, Magna Graecia University, 88100, Catanzaro, Italy

    Michele Andreucci

  3. CNR. Institute of Protein Biochemistry (IBP), 80131, Naples, Italy

    Clemente Capasso, Viviana De Luca & Vincenzo Carginale

  4. Italian Space Agency, La Sapienza University, 00161, Rome, Italy

    Mariano Bizzarri

  5. National Cancer Institute G. Pascale, 80131, Naples, Italy

    Antonella Borrelli, Antonella Schiattarella & Aldo Mancini

  6. Department of Surgery, University Federico II of Naples, 80131, Naples, Italy

    Michele Santangelo

Authors
  1. Antonio Pisani
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  2. Massimo Sabbatini
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  11. Antonella Schiattarella
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  13. Aldo Mancini
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Correspondence to Eleonora Riccio.

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Pisani, A., Sabbatini, M., Riccio, E. et al. Effect of a recombinant manganese superoxide dismutase on prevention of contrast-induced acute kidney injury. Clin Exp Nephrol 18, 424–431 (2014). https://doi.org/10.1007/s10157-013-0828-2

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  • DOI: https://doi.org/10.1007/s10157-013-0828-2

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