The effect of Curcumin on Ochratoxin-A induced nephrotoxicity in rats
Sara Damiano (1), Anna Monnolo (1), Francesco Prisco (1), Valentina Iovane (2), Salvatore Florio (1), Roberto Ciarcia (1).
(1) Università degli Studi di Napoli “Federico II”, Dipartimento di Medicina Veterinaria e Produzioni Animale. (2) Dipartimento di Farmacia, Università di Salerno, Fisciano, Italia.
Ochratoxin-A (OTA) is a metabolite produced by Aspergillus ochraceus and Penicillium verrucosum that accumulates in the food chain because of its long half-life. OTA has been shown to induce a tubulointerstitial nephropathy in animals (1) and to be probably involved in the Balkan endemic nephropathy in humans (2). In addition, OTA disrupts blood coagulation and glucose metabolism (3). Anyway, its mechanisms of toxicity remain unclear. Therefore, the focus of this work was to investigate the antioxidant and anti-inflammatory effects of curcumin on OTA-induced nephrotoxicity. Therefore, we have analyzed, on 24 adult Sprague Dawley rats, oxidative stress by the measurement of malondialdehyde production, renal inflammation by western blot of IL12 and IL 6 and renal function by clearance of inulin. Statistical analyses were performed using the GraphPad Software. We found that the animals treated with OTA (0,5 mg/Kg b.w.) by gavage for 14 days reduced the glomerular filtration rate (GFR) measured by clearance of inulin (0.41±0.15 vs 0.98±0.11 ml/min) and this effect is related to the alteration of oxidative stress. In fact, we have found a severe increase in malondialdehyde production (368±15 vs 128±14 pmol/mg of proteins) and a decrease of SOD (23.2±10 vs 42.5±12 U/mg), CAT (263.4±11 vs 352.8±18 U/mg) and GPx (18.6±6 vs 28.2±5 U/mg) enzymatic activity in OTA-treated rats. Moreover, our results have shown that OTA do not induced a significant increase of IL12 (1.02±0.05 vs 0.98±0.08 arbitrary unit) and IL6 (2.08±0.8 vs 2.12±1.1 arbitrary unit) in the kidney of exposed animals for 14 days of OTA. Curcumin (100 mg/Kg b.w.) is able to partially prevent the GFR decrease (0.78±0.8 ml/min) and several effects was found on oxidant (38.5±8 SOD, 304±18 CAT, GPx (25.5 ± 7) and anti-inflammatory (1.12±0.9 IL12 and 2.08±0.8 IL6) pathways. Finally, histopathological examinations revealed a severe tubular vacuolization and atrophy associated with interstitial infiltrate in OTA-treated groups and co-treatment with OTA plus curcumin is associated with a modest restore of these histological parameters. In conclusion, this study demonstrated that there is a strong link between oxidative stress and OTA-induced renal injury in a chronic toxicity rat model and curcumin is able, in part, to prevent this renal injury.
[1] Pfohl-Leszkowicz A et al. Ochratoxin A and aristolochic acid involvement in nephropathies and associated urothelial tract tumours. Arh Hig Rada Toksikol. 60(4):465-83, 2009. [2] Stoev SD. Balkan Endemic Nephropathy - Still continuing enigma, risk assessment and underestimated hazard of joint mycotoxin exposure of animals or humans. Chem Biol Interact, 261:63-79, 2017. [3] Gan F et al. Effects of ochratoxin A on ER stress, MAPK signaling pathway and autophagy of kidney and spleen in pigs. Environ Toxicol, 32(10):2277-2286, 2017.
