# Effects of Curcumin on the Renal Toxicity Induced by Ochratoxin A in Rats
## 4 Discussion
It also appears to exert a protective antioxidant action on the kidney by enhancing the main enzymatic activities, such as SOD and CAT, and reversing the inhibitory effects of oxidative stress induced by OTA on GPx activity. These results indicate that, at least, the anti-stress activity of CURC may be in part due to its antioxidant effect. Here, we also analyzed the functional nephrotoxicity indices, such as BUN and CREA. The increase in BUN is often associated with renal insufficiency while creatinine is commonly used as a renal function measure and is the first step in controlling the glomerular filtration rate (GFR) [48]. BUN and CREA values were elevated in rats treated with OTA. The CURC significantly reduced BUN and CREA values in the serum of rats treated with OTA and this, in accordance with several data in literature, could be due to a reduction in renal damage by the CURC [49; 50; 51]. The increase in CREA observed in rats treated with OTA is related to the GFR reduction, which is associated with oxygen free radicalformation. Actually, oxidative stress can promote the formation of a variety of vasoactive mediators that can affect renal functions directly by causing renal vasoconstriction or decreasing the glomerular capillary ultrafiltration coefficient and, thus, reduce GFR [52]. Instead, CURC in association with OTA completely prevented this renal hemodynamic alteration. The reported histological modifications are comparable to that described in OTA-induced damage in rats [27; 53]. We hypothesized that the OTA-dependent damage of the secondary foot processes of the podocytes may be the cause of the presence of proteins in the Bowman's spaces and tubules lumen and may be the cause of body weight loss [27; 53]. The mechanisms underlying the protective role of the antioxidants toward OTA-related tubular epithelial cell damage is still debatable. We hypothesized that antioxidants, such as CURC, may counteract the production of reactive oxygen species (e.g., superoxide anion, hydroxyl radical and peroxide) and the OTA-induced lipid peroxidation mediated by cytochrome P450 activity in producing OTA-Fe3+/2+ complexes [54; 55]. Decreased collagen degradation through matrix metalloproteinase inhibition and increased collagen cross-links are considered key mechanisms leading to OTA-induced kidney cortex fibrosis [56]. Our results showed a recovery of fibrosis in the OTA plus CURC group compared with the OTA group, suggesting a CURC protective role on the fibrosis development also. The effects of CURC on renal damage have been investigated in animal models, both in vivo and in vitro. Chronic supplementation of CURC has been shown to protect renal damage in various chemically-induced nephrotoxicity and renal injury models [57]. Our morphologic results support the hypothesis that CURC, as other antioxidants [27], reduces glomerular and tubular damage, kidney inflammation and tubulointerstitial fibrosis in rats, potentially preserving kidney function. Our results confirmed that oxidative stress is involved in the OTA nephrotoxicity mechanism. Exposure to OTA induces negative effects and profound changes in kidney functions. CURC showed an improvement in kidney function, biochemical and antioxidant enzyme activities and MDA levels. These observations also were supported by morphologic results such as a reduction in glomerular and tubular damage, in inflammation and in tubulointerstitial fibrosis. Therefore, although further data are needed on the practical application of the CURC, adding it to feed could offset OTA contamination and limit animal exposure to this toxic mycotoxin, thus protecting animal and human health. [PERSON], [PERSON] and R.C., were responsible for planning the study and reviewing the manuscript. [PERSON], [PERSON], [PERSON], [PERSON], [PERSON], [PERSON] and R.C. performed the experiments. All authors read and gave their approval for the final version of the manuscript. No external funding has been received for the present study. The authors are grateful to Dott. [PERSON] for his technical assistance.