Utilization of gallic acid to inhibit some toxic activities caused by Bothrops jararaca or B. jararacussu snake venoms.

Snake bite envenoming is a serious public health issue, affecting thousands of people worldwide every year, especially in rural communities of tropical and subtropical countries. Injection of venom into victims may cause hemorrhaging, blood coagulation imbalance, inflammation, pain, edema, muscle necrosis, and eventually, death. The official validated treatment recommended by governments is the administration of antivenom that efficiently prevents morbidity and mortality. However, this therapy does not effectively neutralize the local effects of Viperidae venoms which constitute one of the leading causes of disability or amputation of the affected limb. Thus, bioprospecting studies seeking for alternative therapies to complement antivenom should be encouraged, especially those investigating the blockage of local venomic toxicity. Plants produce a great diversity of metabolites with a wide range of pharmacological and biological properties. Therefore, the objective of this study was to assess the utilization of gallic acid, which is widely found in plants, against some toxic in vitro (coagulation, proteolytic, and hemolytic) or in vivo (edematogenic, hemorrhagic, and lethal) activities of Bothrops jararaca or B. jararacussu venom. Gallic acid was incubated with B. jararaca or B. jararacussu venom (incubation protocol), after which, in vitro or in vivo assays were performed. Additionally, a gel containing gallic acid was developed and topically applied over the skin of mice after injection of B. jararaca or B. jararacussu venom (treatment protocol), and then, a hemorrhagic assay was carried out. As a result, gallic acid inhibited the toxic activities, with variable efficacy, and the gallic acid gel neutralized B. jararaca or B. jararacussu venom-induced hemorrhagic activity. Gallic acid was devoid of in vitro toxicity as shown through a hemocompatibility test. Thus, these findings demonstrate the potential of gallic acid in the development of an alternative agent to treat victims of snake bites inflicted by Bothrops species.

Inflammatory response and macrophage polarization using different physicochemical biomaterials for oral and maxillofacial reconstruction.

Knowledge about the action of immune system in the recognition of biomaterials has been extremely helpful when it comes about understanding host response and biomaterials' fate in human body. This study aimed to investigate inflammatory response and macrophage polarization during bone healing process of rat's calvaria critical defects using different bone materials in order to evaluate their influence on bone repair and on the quality of the newly formed bone tissue. Eighty male albinus Wistar rats underwent surgical procedure for the confectioning of a 5-mm diameter bone defect in their right parietal bone, and divided in four groups (n = 20 each), according the biomaterial: AG - Control, particulate intramembranous autogenous bone graft, HA/TCP - particulate biphasic calcium phosphate with HA/TCP (60/40), DBB - particulate deproteinized bovine bone, VC - particulate bioactive vitroceramic. After 3, 7, 21, and 45 days, the specimens were removed and prepared for microcomputed tomography (microCT), light and polarized microscopy, immunohistochemical analysis, and histomorphometry. No significant differences were detected considering percentage of leukocytes among the groups and periods, as well as in relation to immunolabeling for inflammatory (M1) and reparative (M2) macrophages. However, immunolabeling for bone marker indicated a delayed osteoblast differentiation in VC group, resulting in a decrease in mineralized bone matrix parameters in this group, revealed by microCT. In addition, AG and HA/TCP presented a satisfactory bone collagenous content. Despite the distinct origins and physicochemical properties of the tested biomaterials, they presented similar immune-inflammatory responses in the present experimental model, influencing bone-related proteins and bone quality, which must be considered according to their use.