Histophatological Changes And Inflammatory Response Induced By Tityus Scorpion Venom In Rams

¹D’Suze, G., ²Salazar, V., ¹Díaz, P., ¹Sevcik, C., ³Azpurua, H. and ³Bracho, N.

1 Laboratory of Cellular Neuropharmacology, 2 Light Microscopy Service, 3 Experimental Surgery Unit, IVIC, Apdo. 21827 Caracas 1020A, Venezuela.

Anesthetized rams envenomed s.c. with 40 mg/kg Tityus discrepans scorpion venom developed fasciculation, hypothermia, polyuria, pulmonary wet rales, tachypnea, respiratory distress and arrhythmia. Rams developed a cascade of inflammation reactions, characterized by activation of macrophages, fibroblasts and neutrophils, neutrophil infiltration and aggregation, vasculitis, arteritis and abundant fibrin deposition. These are common features of activation of an Arthur reaction. At the inoculation site, venom was detected by immunohistochemistry in the extra cellular matrix, lymphatic vessels’ and venules’ lumen, inside macrophages and surrounding nerves. Extra cellular matrix was degraded at the inoculation site perhaps by activated neutrophils. Envenoming produced hepatocytes with Mallory body-like vacuoles which may be due to increased levels of TNF-a and IL6. Pancreatic acini were degranulated, vacuolised necrotised, with interstitial swelling, and Langerhan’s islets were altered. Lungs developed the most deleterious effect developing alveolar wall collapse and necrosis, diffuse injury of the alveolar capillary barrier, interstitial and alveolar fibrin deposits with strong neutrophil infiltration. A massive infiltration of lymphocytes and macrophage occurred in the intestinal submucose, to the extent that it modified villi and intestinal folding morphology. Leukocyte migration may be stimulated by adhesion molecules produced by endothelial cells and/or fibroblasts. A marked leukocyte aggregation surrounded nerves at the inoculation site. This study reveals that beyond its neurotoxicity, Tityus venom produces a severe and widespread inflammatory syndrome, expressed as histopathological changes at the site of inoculation, as well as in remote organs such as pancreas, lungs, intestine and liver. Our results suggest that not all remote targets are directly affected by the venom but that, as proposed earlier, are modified by inflammation by products produced elsewhere. 

Support : partially supported by IVIC-SILANES grant for applied projects N°: 2001-31 (GDS) and by Venezuelan FONACIT grant N°: S1-2001000908 to GDS.

Correspondence to: gdsuze@ivic.ve