Pathomorphology of subchronic effect of low doses of ochratoxin a on liver, lymphoid organs and testes in wistar rats

The effects of subchronic exposure to OTA (at very low levels) on different organs was studied in seven-weeks-old male Wistar rats gavaged with OTA @ 0.25 mg and 0.50 mg OTA/kg body weight (group A and group B, respectively), daily for four weeks. The third group of rats, given only vehicle served as a control. Pathomorphological changes in liver, spleen, mesenteric lymph nodes, Peyer's patches and testes were studied at regular intervals of 2 days and 1, 2, 3 and 4 weeks of OTA-treatment, besides ultrastructural studies at the end of 4th week post OTA exposure. Liver of OTA-treated rats showed nonsignificant increase in catalase and superoxide dismutase, while malondialdehyde levels were significantly increased in group-B rats. Grossly, no appreciable changes were observed in group-A. In Group-B, liver was comparatively friable and fragile from 3rd week onwards. Spleen was congested and reduced in size. Peyer's patches were significantly smaller in size. Testes were shrunken, atrophic and the relative weight was significantly reduced. Histopathological changes were characterized by severe degenerative changes in the liver, depletion of lymphocytes in the spleen, mesenteric lymph nodes and Peyer's patches with occurrence of apoptotic cells in the depleted lymphoid follicles. Testes showed complete loss of spermatogenic activity due to degeneration of spermatogonial cells and formation of multinucleated cells. Hepatocytes of OTA-treated rats showed depletion of glycogen. Ultrastructural changes were cytoplasmic vacuolations, disorganized and/or loss of cristae in the mitochondria, degranulation of rough endoplasmic reticulum, sparse distribution of glycogen granules and paucity of several organelles in the hepatocytes. Spleen showed lymphocytes in various stages of degeneration with pyknotic nuclei. Macrophages containing degenerated and disintegrating nuclei of lymphocytes were also seen. It was concluded that subchronic oral exposure of OTA induced significant dose dependent pathological changes in rats.