The effect of a Red orange and Lemon Extract on Ochratoxin-A induced nephrotoxicity in rats
Sara Damiano, Caterina Squillacioti, Andrea Ariano, Francesco Prisco, Salvatore Florio, Roberto Ciarcia.
Università degli Studi di Napoli “Federico II”, Dipartimento di Medicina Veterinaria e Produzioni Animale.
Ochratoxin A (OTA) is the most widespread and dangerous mycotoxin which contaminates various food commodities including grains, dried fruits, nuts, coffee, meat products, wine and beer (1). The high thermal stability makes the eradication of OTA from the food chain very difficult (2). Its sub-chronic and sub-chronic toxicity in humans and in several animal species includes nephrotoxicity, neurotoxicity, teratogenicity, immunotoxicity and hepatotoxicity (3); however, several studies demonstrated that the kidney is the target organ (3). Since the mechanism underlying such effects remain unclear, the focus of this work was to investigate the antioxidant effects of a by-products natural Red orange and Lemon Extract (RLE), rich in anthocyanins and phenols, on OTA-induced nephrotoxicity. We have analyzed, on 24 adult Sprague Dawley rats, oxidative stress by the measurement of malondialdehyde production and by SOD and GPx parameters by ELISA Kit; renal function by clearance of inulin and histological examination by haematoxylin eosin‐ and Masson's trichrome staining. Statistical analyses were performed using the GraphPad Software.The rats were treated with OTA (0,5 mg/Kg b.w.) and/or RLE (90 mg/ kg b.w.) by gavage for 14 days. We demonstrated that several oxidative stress indicators were altered in the kidneys (1.5±0.04 vs 2.0 ±0.06 umol/l in GPx and 62.9% vs 100% on inhibition in SOD) coupled to a strong reduction of Glomerular Filtration Rate (GFR) (0.51±0.8 vs 0.86±0.08 ml/min), to a body weight decrease (315±22 vs 364±19 gr) and an increase of serum creatinine (1.25±0.08 vs 0.92±0.09 mg/dL) and urea levels in serum (22.8±5.25 vs 18.12±4.45 mg/dL). Histopathological examinations revealed tubular and glomerular necrosis in OTA-treated groups. Moreover, OTA treatment induced a more severe interstitial fibrosis compared to control group. Co-treatment of RLE and OTA was associated with a partially restore of fibrosis and tubular and glomerular necrosis compared to the OTA group. Treatment with RLE restored the body weight, normalized the reactive oxygen species and prevented the glomerular hyperfiltration. In conclusion, this study demonstrated that there is a strong relation between oxidative stress and OTA-induced renal injury and that RLE prevents this renal injury.
[1] Covarelli et al. A review on the occurrence and control of ochratoxigenic fungal species and ochratoxin a in dehydrated grapes, non-fortified dessert wines and dried vine fruit in the mediterranean area, Food Control, 21:347–356, 2012. [2] Duarte et al. Ochratoxin A non-conventional exposure sources—A review, Microchem. J, 93:115–120, 2009. [3] Pfohl-Leszkowicz et al. Balkan endemic nephropathy and associated urinary tract tumours: a review on aetiological causes and the potential role of mycotoxins, Mol. Nutr. Food Res, 51:1192–1192, 2007.
