# Effects of Curcumin on the Renal Toxicity Induced by Ochratoxin A in Rats
## 1 Introduction  
Ochratoxin A (OTA) is a mycotoxin derived from the secondary metabolism of different fungi genera, in particular it originates from _Aspergillus ochraccus_, _A. carbonarius_, _A. niger and Pencilillium verrtcosum_, in tropical areas and in temperate climate regions, respectively [1]. OTA is generally found in all types of cereals and derived products, but also in coffee, cocoa, grapes, soy, spices, legumes, nuts, licorice, wine, and beer [2; 3; 4]. OTA is often the cause of chronic toxicity, due to the prolonged intake of its small amounts, and manifests itself with carcinogenic, genotoxic, teratogenic, nephrotoxic and immunosuppressive effects [5; 6; 7] both on humans and numerous animal species. Previous studies have found that its presence in food for human use can induce chronic kidney diseases, such as Endemic Balkan Nephropathy which leads, in a period of 6-10 years, to irreversible renal failure [8; 9]. Added to an indirect contamination, which occurs with the ingestion by animals of naturally contaminated feed, subsequent passage, and accumulation of OTA in tissues (carry over), a direct contamination is possible. This kind of contamination is linked to the growth of molds producing OTA on the meat productsduring the seasoning or the addition of contaminated spices during the product processing [10]. Among the production animals, the risk is limited to monogastric species since ruminants can hydrolyze the OTA amide bond by forming a non-toxic compound [11]. Particularly, pigs are the most sensitive to the accumulation of OTA, which is deposited in the tissue level following the kidney \(>\) liver \(>\) muscle \(>\) fat model [12]. Therefore, the European Communities Commission recommends a guide value of OTA that should not exceed 0.05 mg/kg in complementary and complete feeds intended for pigs [11]. Indeed, intoxication by OTA is considered not only a sanitary, but also an economic problem. The chronic OTA-intake through contaminated feeds causes significant production losses in the zootechnical environment linked to the decrease of food intake, production yields, and fertility in animals [13]. The toxic action of OTA mostly affects kidneys, but other organs, such as the liver, and the immune system are involved [14]. Although, even if the effects of OTA are known, the molecular mechanisms that regulate its effects still are not completely clarified. However, it is estimated that oxidative stress and the phlogistic state are responsible for OTA-induced nephrotoxicity. Phytochemicals use, thanks to their anti-inflammatory and antioxidant effects, has emerged as a potential approach to reduce chronic renal failure. Therefore, in this study we evaluate the efficacy of curcumin (CURC) on OTA-induced nephrotoxicity. CURC is a polyphenic compound that derives from the rhizome of Curcumin longa Linn, belonging to Zingiberaceae family. Several studies demonstrate that CURC has numerous pharmacological antioxidants [15], anti-inflammatory [16], antiviral and antibacterial properties [17], as well as its therapeutic potential effect on tumors [18]. CURC has shown to inhibit inflammatory processes and to be a powerful scavenger of both reactive oxygen species (ROS) and reactive nitrogen species (RNS), as well as to preserve the renal mitochondrial redox balance during acute and chronic nephrotoxicity [19]. CURC has a strong antioxidant action by acting directly on reactive oxygen species, by reducing the levels of anion superoxide (O\({}_{2}\)\({}^{-}\)), peroxynritrite (ONOO\({}^{-}\)), nitric oxide (NO), peroxyl radicals (HO\({}_{2}\)) and hydroxyl radicals (OH\({}^{-}\)) [16]. Particularly, the antioxidant activity of CURC is linked to its phenolic groups which, reacting with ROS, protects cells from oxidative damage. Furthermore, CURC is able, indirectly, to induce the over-expression of antioxidant proteins such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx).