A new recombinant MnSOD prevents the cyclosporine A-induced renal impairment

Sara Damiano, Francesco Trepiccione, Roberto Ciarcia, Roberto Scanni, Manuela Spagnuolo, Leonida Manco, Antonella Borrelli, Clemente Capasso, Roberto Mancini, Antonella Schiattarella, Anna Iervolino, Enza Zacchia, Andrea Bata-Csere, Salvatore Florio, Pietro Anastasio, Rosamaria Pollastro, Aldo Mancini, Giovambattista Capasso

Research output: Contribution to journalArticlepeer-review

Abstract

Background. Cyclosporine A (CsA) is one of the most frequently used anticalcineurinic drugs for preventing graft rejection and autoimmune disease. Its use is hampered by nephrotoxic effects, namely an impairment of the glomerular filtration rate (GFR) and hypertension. Evidence suggests that reactive oxygen species (ROS) play a causal role in the nephrotoxicity. The present study aims to investigate in vivo the effects of a new recombinant mitochondrial manganese-containing superoxide dismutase (rMnSOD), a strong antioxidant, on the CsA-induced nephotoxicity. Methods. Rats were treated with CsA (25 mg/kg/day) alone or in combination with rMnSOD (10 μg/kg/day) for 7 days. At the end of the treatment, GFR was estimated by inulin clearance (mL/min/100 g b.w.) and the mean arterial pressure (MAP) was recorded through a catheter inserted in the carotid artery. Superoxide concentration within the cells of the abdominal aorta was quantified from the oxidation of dihydroethidium (DHE). In kidney tissues, ROS levels were measured by the 2′7′ dichloroflurescin diacetate assay. Renal morphology was examined at the histochemistry level. Results. CsA-treated rats showed a severe decrease in GFR (0.34 ± 0.17 versus 0.94 ± 0.10 in control, P <0.001) which was prevented by rMnSOD co-administration (0.77 ± 0.10). CsAinjected animals presented with higher blood pressure which was unaffected by rMnSOD. ROS levels both in the aorta and in renal tissue were significantly increased by CsA treatment, and normalized by the co-administration with rMnSOD. This effect was, partly, paralleled by the recovery from CsA-induced morphological lesions. Conclusions. Administration of rMnSOD prevents CsA-mediated impairment of the GFR along with morphological alteration. This effect could be related to the inhibition of ROS.

Original languageEnglish
Pages (from-to)2066-2072
Number of pages7
JournalNephrology Dialysis Transplantation
Volume28
Issue number8
DOIs
Publication statusPublished - Aug 2013

Keywords

  • Cyclosporine
  • Nephrotoxicity
  • Reactive oxygen species
  • Superoxide dismutase

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

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