Swiss mice CD1 fed on mussels contaminated by okadaic acid and yessotoxins: effects on thymus and spleen

The toxicity of okadaic acid (OA) and yessotoxins (YTXs) was studied in mice orally fed on (i) OA (17.80 +/- 2.41 mu g/kg) for 24 h and mouse feed for 24 h; (ii) CA (17.2 +/- 2.13 mu g/kg) plus YTXs (1.30 +/- 0.12 mg/kg)_for 24 h and mouse feed for 24 h; (iii) OA (18.88 +/- 1.86 Ig/kg) plus YTXs (1.45 +/- 0.12 mg/kg) for 24 h. After toxin treatments the thymus and spleen were examined. More severe morpho-functional modifications were found in the thymus, which presented atrophy, a significant depletion in the lymphoid compartment and angiogenesis. In spite of the impairment, a number of inflammatory cells, reactive to anti-cytokine antibodies, were recruited. Moreover, greater expression of matrix metalloproteinase-9, particularly in cells located near new blood vessels, was observed. Thymus injury was still observed after 48 h. Histopathological changes to the spleen were more evident in mice orally treated for 24 h and immediately sacrificed. The organ showed a significant loss of volume and a fibrous component invaded regions involved in immune functions. In white pulp the marginal zones were reduced, lymphoid nodules contained large germinal centres and the periarteriolar lymphoid sheaths showed cellular depletion. An inflammatory cell response was activated by the recruitment of granulocytes, an increased number of active macrophages and increased immunoreactivity to cytokines. Unlike in the thymus, some evidence of recovery was seen in the spleen. The data suggest that low oral doses of OA alone or OA plus YTXs are able to provoke immunostimulation and systemic immunotoxicity, thus also indicative of tumorigenic properties.