Laboratoire de recherche sur les substances biologiquement compatibles (LRSBC), Faculté de médecine dentaire, Rue Avicenne, 5019 Monastir, Tunisie <hassen.bachafmdm.rnu.tn>
- Key words: ochratoxins; haematologic diseases; kidney diseases; animal experimentation; rats.
- Page(s) : 221-30
- Published in: 2003
Ochratoxin A (OTA), a mycotoxin produced by species of Aspergillus and Penicillium genera, contaminates various components of the human and animal food chains. OTA is nephrotoxic, genotoxic, cytotoxic, immunosuppressive, teratogenic and carcinogenic, although the mechanisms for these effects have not yet been elucidated. It may be a causal agent of the form of chronic interstitial nephropathy of unknown etiology discovered in Tunisia, which resembles Balkan endemic nephropathy (BEN). We performed two studies to reproduce this human nephrotoxicity in an animal model, show the involvement of OTA in it and highlight other toxic effects induced by this toxin. The first study administered OTA orally to rats (0.4 and 0.8 mg\kg of body weight) under chronic intoxication conditions (regular treatment for 3 months). The toxin dose was low because of the long period of treatment and because of its possible accumulation in the kidneys. Under these conditions, the animals‘ body weight decreased significantly, as did the relative weight and mean size of the kidneys. In addition, the toxin accumulated primarily in the kidneys and to a lesser degree in the blood, whereas the amounts eliminated in the urine remained low. Histological study of the kidneys showed degeneration of tubular tissue and the appearance of karyomegalic cells and abnormal mitosis at an early stage (after 15 days). We noted frequent apoptotic bodies after 3 months. To confirm the role of OTA in nephrotoxicity and to test its other possible toxic effects, we performed a second study in which OTA was administered to rats intraperitoneally (0.6, 1.2 and 2 mg of OTA\kg of body weight) in sub‐acute conditions (treatment by single dose of OTA for 48 h). Because of the short treatment period, we used higher doses to obtain an immediate visible effect. Under these conditions, we observed significant modifications of biochemical and hematological parameters, particularly those involved in renal function. Taken together, our results show that the animal model described here has functional and histological similarities with Balkan endemic nephropathy, the nephropathy observed in Tunisia ; they suggest that OTA is probably responsible for toxic effects in addition to nephrotoxicity.