Relaxant effects of aflatoxins on isolated guinea pig trachea

Abstract

Dyspnea is one of the symptoms of acute aflatoxicosis. Contrary to expectations, we observed that naturally occurring aflatoxins (AF) AFB1, AFB2, AFG1, and AFG2 and their major metabolites AFM1, AFM2, AFP1, AFQ1, and AFG(2a) relaxed carbachol (C) precontracted guinea pig trachea to different degrees. The efficacies but not the potencies of AFB1, AFB2, AFG1, and AFG2 were similar to that of the β-agonist, isoprenaline, whose activity was potentiated by the AF. Their mechanism of action is not clearly understood but several mechanistic indications were obtained with AFB1: 1) its effect was not influenced by the β-blocker, timolol, indicating that a direct interaction with β2-adrenergic receptors was not involved. 2) AFB1 potentiated PGE1 and PGE2, two relaxant prostaglandins, and its activity was reduced by indomethacin. 3) The cAMP level in the guinea pig trachea relaxed by AFB1 increased, possibly due to inhibition of phosphodiesterase; direct interaction with PG receptors; and/or interaction with A2 adenosinic receptors, suggested by the inhibitory activity of XAC, a specific antagonist. 4) Finally, since tetrodotoxin reduced the relaxant activity of AFB1, it is speculated that this mycotoxin could stimulate inhibitory nonadrenergic, noncholinergic nerves (i-NANC). In conclusion, the symptoms of acute aflatoxicosis do not seem to be due to a direct activity on the tracheal muscle, but rather, to the well-known pro-inflammatory activity of the aflatoxins, which are capable of releasing arachidonic acid from cell membranes.