Toxic effects of Senecio brasiliensis on rat phagocytes

Abstract

s / Toxicology Letters 196S (2010) S37–S351 S199 P205-022 Allergen-stimulated expression of interleukin (IL)-17 isoforms in mice I. Kimber, M. Hayes, R. Dearman University of Manchester, United Kingdom The development of immune and allergic responses is orchestrated by T helper (Th) subsets that are characterized by selective cytokine secretion profiles. Topical exposure of BALB/c strain mice to different classes of chemical allergen has been shown to result in preferential activation of divergent Th cell subsets. Thus, Th1 and Th2 cells are induced by the contact allergen 2,4-dinitrochlorobenzene (DNCB) and the respiratory sensitizer trimellitic anhydride (TMA), respectively. A further subset of inflammatory Th cells that secrete IL-17mayplay an important role in some autoimmune and inflammatory conditions. In the current investigations, the ability of chemical allergens to provoke changes in expression of the expression of IL-17 isoforms has been examined. BALB/c strain mice were exposed to a single topical dose of either 1% DNCB or 25% TMA, or to vehicle alone, for 30min to 72h. At various times thereafter, cytokine production by skin explants (prepared from dorsal halves of ear tissue) or by draining auricular lymph node cells (LNC) was measured by cytokine-specific enzyme-linked immunosorbant assay (ELISA). Topical treatment with DNCB, but not to TMA or vehicle alone, provoked a rapid increase in IL-17A and IL-17F isoforms, peaking at 2–3h. Levels of IL-17F were generally some 5-fold higher than those observed for IL-17A. DNCB-activated LNC also produced high levels of both IL-17A and IL-17F, reaching maximal levels after 6h of exposure. The heterodimer (IL-17A/F) was also detected, but at considerably lower levels. Treatment with TMA induced the same pattern of cytokines in the draining lymph node, but with slightly delayed kinetics, peaking at 48–72h. These data demonstrate that chemical allergens provoke the rapid production of IL-17 isoforms in the skin and draining lymph node which may play a role in the acquisition of sensitization. doi:10.1016/j.toxlet.2010.03.673 P205-023 Toxic effects of Senecio brasiliensis on rat phagocytes F. Elias1, I. Hueza2, A. Latorre1, S. Gorniak1 1 University of Sao Paulo/Research Center of Veterinary Toxicology (CEPTOX), Brazil, 2 Federal University Of Sao Paulo/School of Pharmacy and Biochestry, Brazil Senecio brasiliensis is one of the most toxic poisonous plant species of Senecio’s genus. It contains pyrrolizidine alkaloids (PAs) that are associated with disease in livestock and human beings after be metabolized into the liver in a high reactive electrophiles (pyrrol compound) capable to link with cellular macromolecules, mainly DNA, forming adducts which may initiate acute or chronic toxicity. The development of oxidative stress with the generation of superoxides and lipid-peroxy radicals in PAs toxicity in cattle and cytotoxicity to macrophages mediated by reactive oxygen species were recently documented. Therefore, the aim of this study was to verify if S. brasiliensis induce toxicity in innate immune system cells (macrophages and neutrophils) during phagocytosis activity. PAs was extracted and concentrated into a butanolic residue (BR) and rats were then treated with BR daily, by gavage, during 28 days. Two experiments were performed, one to evaluate peritoneal macrophages and the other to determine peripheral neutrophils activity. For each experiment 40 adult rats were separated into four groups treated with 0.0 (control), 3.0 (A), 6.0 (B), and 9.0 (C)mg/kg of BR. The results obtained showed a significant enhancement in basal (Aand C-group) and PMA induced (C-group) oxidative burst of peritoneal macrophages and also an increase percentage of macrophage phagocytosis (A-, B-, and Cgroup). However, in relation to neutrophils activities, it was only observed an increase in basal oxidative burst (Aand B-group). The intracellular redox potential is maintained in a reduced state by constant elimination of superoxides, peroxides and cellular H2O2 by glutathione (GSH). The pyrrolic metabolites produced from PAs are capable tobindwithGSHto formGSHconjugates. Thus, it is possible to hypothesized that, one of themechanism that S. brasiliensis exerts its immunotoxicity onmacrophage and neutrophil activities is by depleting GSH. doi:10.1016/j.toxlet.2010.03.674 P205-024 Inflammatory response to orthopaedic cobalt chromium alloy wear debris in a rodent air pouch model M. Akbar1, M.H. Grant1, J. Brewer2 1 University of Strathclyde, United Kingdom, 2 University of Glasgow,