Venom of the giant ant Dinoponera quadriceps attenuates inflammatory pain in mouse cutaneous wound healing model

Arthropod venoms are potential sources of bioactive substances, providing tools for the validation of popular use and new drugs design. Ants belonging to the genus Dinoponera are used in the folk medicine to treat inflammatory conditions. It was previously demonstrated that the venom of the giant ant Dinoponera quadriceps (DqV), containing a mixture of polypeptides, elicit antinociceptive effect in mice models of chemical, mechanical and thermal nociception. The aim of this study was to evaluate DqV antiinflammatory and antihypernociceptive effects in a mice model of traumatic cutaneous wound. Colonies of D. quadriceps were collected in the ‘‘Serra de Maranguape’’ (State of Ceará, northeastern Brazil), a small mountain range located on the coastal zone, and the venom secreted by the ant glands was extracted with capillary tubes, further lyophilized and maintained at -20 ± 1ºC until use. Wounds were performed in the dorsum of Swiss mice. Animals received intravenous (i.v.) injection of DqV (50 µg -1kg day-1) during 3 days for evaluation of inflammatory parameters present in the wounds: hypernociception, leukocyte infiltrate, myeloperoxidase activity, nitrite nitrate-1 content. Data was tested by two-way ANOVA and Bonferroni’s post-hoc test. DqV reduced (2.7 folds) hypernociception at 48 hours, leukocyte infiltration by 65% at 6 hours and myeloperoxidase activity by 60% at 0.5 hour after wound induction. In conclusion, the venom extracted from D. quadriceps glands attenuates inflammation and hypernociception in mice cutaneous wounds.

Role of Hyperplasia of Gingival Lymphatics in Periodontal Inflammation.

Lymphatic vessels are important for maintenance of tissue fluid homeostasis and afferent antigen transport. In chronic inflammation, lymphangiogenesis takes place and is characterized by lymphatic endothelial cell proliferation and lymphatic hyperplasia. Vascular endothelial growth factor C (VEGFC) is the main known lymphangiogenic growth factor, and its expression is increased in periodontitis, a common chronic infectious disease that results in tissue destruction and alveolar bone loss. The role of lymphangiogenesis during development of periodontitis is unknown. Here, we test if transgenic overexpression of epithelial VEGFC in a murine model is followed by hyperplasia of lymphatic vessels in oral mucosa and if the lymphatic drainage capacity is altered. We also test if lymphatic hyperplasia protects against periodontal disease development. Transgenic keratin 14 (K14)-VEGFC mice had significant hyperplasia of lymphatics in oral mucosa, including gingiva, without changes in blood vessel vasculature. The basal lymph flow was normal but slightly lower than in wild-type mice when oral mucosa was challenged with lipopolysaccharide from Porphyromonas gingivalis. Under normal conditions, K14-VEGFC mice exhibited an increased number of neutrophils in gingiva, demonstrated enhanced phagocyte recruitment in the cervical lymph nodes, and had more alveolar bone when compared with their wild-type littermates. After induction of periodontitis, no strain differences were observed in the periodontal tissues with respect to granulocyte recruitment, bone resorption, angiogenesis, cytokines, and bone-related protein expressions or in draining lymph node immune cell proportions and vascularization. We conclude that overexpression of VEGFC results in hyperplastic lymphatics, which do not enhance lymphatic drainage capacity but facilitate phagocyte transport to draining lymph nodes. Hyperplasia of lymphatics does not protect against development of ligature-induced periodontitis.