Effect of rMnSOD on sodium reabsorption in renal proximal tubule in Ochratoxin A - treated rats

Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus and Penicillium that represent toxic real threat for human beings and animal health. In this study we evaluated the effect of a new recombinant mitochondrial manganese containing superoxide dismutase (rMnSOD) on oxidative stress and on the alterations of fluid reabsorption in renal proximal tubule (PT) as possible causes of OTA nephrotoxicity. Finally, we have measured the concentration of O2 - in the kidney through dihydroethidium assay (DHE) and nitric oxide (NO) concentration through nitrites and nitrates assay. Male Sprague Dawley rats weighing 120-150 g were treated for 14 days by gavage, as follows: Control group, 12 rats received a corresponding amount of saline solution (including 10% DMSO); rMnSOD group, 12 rats treated with rMnSOD (10 μg/kg bw); OTA group, 12 rats treated with OTA (0,5 mg/Kg bw) dissolved in 10% DMSO and then scaled to required volume with corn oil; rMnSOD + OTA, 12 rats treated with rMnSOD (10 μg /kg bw) plus OTA (0,5 mg/Kg bw). Our results have shown that rMnSOD restores the alteration of reabsorption in PT in rats treated with OTA plus rMnSOD, probably through the response to pressure natriuresis, where nitric oxide plays a key role. Moreover, rMnSOD prevents the nephrotoxicity induced by OTA probably restoring the balance between superoxide and NO that is most probably the cause of hypertension and renal functional alterations through the inhibition of NO synthase. In conclusion these data provide important information for understanding of mechanism of toxic action of OTA.