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Subchronic effects of ochratoxin A on young adult rat brain and partial prevention by aspartame, a sweetener

Laboratory of Toxicology and Applied Hygiene, 146, rue Léo Saignat, 33076 Bordeaux CEDEX

G Tramu

Laboratory of Functional Neurocytochemistry, Av des Facultés, 33045 Talence CEDEX France

A M Betbeder

Laboratory of Toxicology and Applied Hygiene, 146, rue Léo Saignat, 33076 Bordeaux CEDEX

E E Creppy

Laboratory of Toxicology and Applied Hygiene, 146, rue Léo Saignat, 33076 Bordeaux CEDEX

1. Ochratoxin A (OTA) is a mycotoxin produced by several fungi, especially Aspergillus and Penicillium species. Many food and foodstuffs can be contaminated by ochratoxin A, which is consequently found in blood of animals and humans.

2. The distribution into the brain of young adult rats fed OTA for 1 to 6 weeks and some consequences have been investigated in the present study.

3. Our results on rats given OTA (289 mg/kg/48 h) indicated that OTA accumulated in the whole brain as function of time according to a regression curve, Y=78.723 a+16.72 with a correlation coefficient of r=0.989, where Y-axis is the OTA concentration in ng/ g of brain and X-axis is the duration of the treatment in weeks. The brain OTA contents was 11.95+2.2, 23.89+4.4, 39.9+4.5, 50.3+7.3, 78.8+6.3, 94+16 ng/g of brain in the mycotoxin-treated animals for respectively 1, 2, 3, 4, 5 and 6-weeks treatment. OTA induced modifications of free amino-acid concentrations in the brain, mainly, Tyrosine (Tyr) and phenylalanine (Phe). Tyr decreased significantly as compared to control (p50.05). Phe increased signifi-cantly as compared to control (p<50.05).

4. Aspartame, (25 mg/kg/48 h) a structural analogue of OTA largely modified the distribution and prevented the accumulation of OTA in the brain since the respective brain OTA contents decreased respectively to 9.6+7.9, 19.2+3.0, 26.8+4.2, 19.7+1.9, 13.7+5.6 and 11.0+6.0 ng/g of tissue, for the same duration of treatment. It also prevented the modifications of Tyr and Phe levels.

5. The histological investigations showed several necrotic cells with pyknotic nucleus, detected in OTA treated animals with higher frequency as compared to the controls and Aspartame treated ones. Aspar-tame appeared to significantly prevent this nuclear effect as well, the meaning of which is discussed.

Key Words: ochratoxin A • subchronic intoxication • rat brain • aspartame (ASP) • phenylalanine • tyrosine • prevention

Human & Experimental Toxicology, Vol. 17, No. 7, 380-386 (1998)
DOI: 10.1177/096032719801700704


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