Curcumin Modulates Nitrosative Stress, Inflammation, and DNA Damage and Protects against Ochratoxin A-Induced Hepatotoxicity and Nephrotoxicity in Rats.

Consiglia Longobardi,Valeria Russo,Sara Damiano,Salvatore Florio,Francesco Pagnini,Francesco Prisco,Emanuela Andretta,Roberto Ciarcia

doi:10.3390/antiox10081239

Abstract

Ochratoxin A (OTA) is a fungal toxin of critical concern for food safety both for human health and several animal species, also representing a cancer threat to humans. Curcumin (CURC) is a natural polyphenol that has anti-apoptotic, anti-inflammatory, and antioxidant effects. The aim of this study was to investigate the cytoprotective effect of CURC against OTA-induced nephrotoxicity and hepatotoxicity through the study of the nitrosative stress, pro-inflammatory cytokines, and deoxyribonucleic acid (DNA) damage. Sprague Dawley rats were daily treated with CURC (100 mg/kg b.w.), OTA (0.5 mg/kg b.w), or CURC with OTA by oral gavage for 14 days. Our results demonstrated that OTA exposure was associated with significant increase of pro-inflammatory and DNA oxidative-damage biomarkers. Moreover, OTA induced the inducible nitric oxide synthase, (iNOS) resulting in increased nitric oxide (NO) levels both in kidney and liver. The co-treatment OTA + CURC counteracted the harmful effects of chronic OTA treatment by regulating inflammation, reducing NO levels and oxidative DNA damage in kidney and liver tissues. Histology revealed that OTA + CURC treatment determinates mainly an Iba1+ macrophagic infiltration with fewer CD3+ T-lymphocytes in the tissues. In conclusion, we evidenced that CURC exerted cytoprotective and antioxidant activities against OTA-induced toxicity in rats.

Highlights

Ochratoxin A (OTA) is a toxic secondary metabolite generated by several filamentous chlorophenolic fungal species belonging to Aspergillus and Penicillium genera [1,2].it is a food contaminant present in a large variety of agricultural products, including cereals, cereal-based products [3], grapes [4], herbs, coffee, cocoa, tea, fish, pork, milk and its products, poultry, and eggs [5,6]
OTA is a mycotoxin which causes serious health problems in both humans and animals, and we considered necessary in this work to investigate the main biochemical mechanisms of action underlying the toxic effects related to this mycotoxin
The purpose of this study was to assess if CURC, a natural polyphenol compound used as an herbal medicine for inflammatory diseases, had potential protective role on OTA-promoted nitrosative stress, deoxyribonucleic acid (DNA) injury and, especially, inflammation in rat liver and kidney tissues

Summary

Introduction

Ochratoxin A (OTA) is a toxic secondary metabolite generated by several filamentous chlorophenolic fungal species belonging to Aspergillus and Penicillium genera [1,2]. It is a food contaminant present in a large variety of agricultural products, including cereals, cereal-based products [3], grapes [4], herbs, coffee, cocoa, tea, fish, pork, milk and its products, poultry, and eggs [5,6]. OTA is a danger both for people exposed to food diets containing OTA and animals. The last European Food Safety Authority (EFSA) evaluation in 2006 and the international experts of the World Health Organization (WHO) stated

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