Background: Snakebite envenomation (SBE) causes diverse toxic effects in humans, including disability and death. Current antivenom therapies effectively prevent death but fail to block local tissue damage, leading to an increase in the severity of envenomation; thus, seeking alternative treatments is crucial. Methods: This study analyzed the potential of two fucoidan sulfated polysaccharides extracted from brown seaweeds Fucus vesiculosus (FVF) and Undaria pinnatifida (UPF) against the fibrinogen or plasma coagulation, proteolytic, and phospholipase A₂ (PLA₂) activities of Bothrops jararaca, B. jararacussu, and B. neuwiedi venom. The toxicity of FVF and UPF was assessed by the hemocompatibility test. Results: FVF and UPF did not lyse human red blood cells. FVF and UPF inhibited the proteolytic activity of Bothrops jararaca, B. jararacussu, and B. neuwiedi venom by approximately 25%, 50%, and 75%, respectively, while all venoms led to a 20% inhibition of PLA₂ activity. UPF and FVF delayed plasma coagulation caused by the venoms of B. jararaca and B. neuwiedi but did not affect the activity of B. jararacussu venom. FVF and UPF blocked the coagulation of fibrinogen induced by all these Bothropic venoms. Conclusion: FVF and UPF may be of importance as adjuvants for SBE caused by species of Bothrops, which are the most medically relevant snakebite incidents in South America, especially Brazil.

Cardiovascular disease is the major cause of death worldwide; therefore, it is important to understand the natural history of the pathophysiologic process and develop strategies to halt its progression. Thus, this study investigated the protective effect of aerobic training on pathophysiological mechanisms involved in subclinical cardiometabolic alterations in a model with constant exposure to a prejudicial agent. Male Wistar rats were divided into Control group (C), which received drinking water, Fructose group (F), which was fed 10% fructose in drinking water for 10 weeks; Control Training group (CT) and Fructose Training group (FT), in which moderate aerobic training was added in the last 8 weeks of the study. Insulin, triacylglycerol and isoprostane were higher and superoxide dismutase (SOD) was lower in the F group. There was no difference in thoracic aorta histology, but it was seen a decreased vascularization in F group, avoided by training in left ventricle. Regarding vascular function, the F group exhibited increased vasoconstrictory reactivity to phenylephrine. The F group presented impaired vasodilation to acetylcholine. Regarding endothelial nitric oxide synthase (eNOS), the F group presented a lower expression, and phosphorylated eNOS was higher in the trained groups than in their respective control groups. This same pattern was observed for nitric oxide (NO) bioavailability, antioxidants protein expression in aorta, left ventricle and muscle (catalase, SOD and glutathione peroxidase), serum SOD activity and muscle mass. These results suggest that exercise training enhanced the antioxidant pathway and as consequence the eNOS pathway, preventing an impairment in vascular vasodilatory capacity.

Animal models are widely used to study the physiopathology of human diseases. However, the influence of gender on modern society diet style-induced cardiovascular disease was not exploited so far. Thus, this study investigated cardiovascular remodeling in C57BL/6J mice fed a diet rich in saturated fat, sucrose, and salt, evaluating gender effect on this process. Male and female C57BL/6J mice were fed AIN93M diet or a modified AIN93M rich in fat, sucrose, and salt (HFSS) for 12 weeks. Body mass, water and food intake and cardiovascular remodeling were assessed. The HFSS diet did not lead to body mass gain or glucose metabolism disturbance assessed by serum glucose, insulin, and oral glucose tolerance test. However, female mice on a HFSS diet had increased visceral and subcutaneous adiposity. Only male mice displayed heart hypertrophy. The left ventricle was not hypertrophied in male and female mice, but its lumen was dilated. Intramyocardial arteries and the thoracic aorta had intima-media thickening in male mice, but in the female, it was only noticed in the thoracic aorta. Finally, intramyocardial artery dilation was present in both genders, but not in the aorta. Changes in LV dimensions and the arterial remodeling were influenced by both gender and the HFSS diet. In conclusion, male and female C57BL/6J mice suffered cardiovascular remodeling after 12 weeks of high-fat, high-sucrose, high-salt feeding, although they did not develop obesity or diabetes. Sexual dimorphism occurred in response to diet for body adiposity, heart hypertrophy, and intramyocardial artery remodeling.

Snakebite envenomation (SBE) is a neglected disease causing annually 138,000 deaths worldwide. In Brazil, the genus Bothrops is responsible for 87% of these SBE. In this work, we assessed the extracts from the plants Aescululs hippocastanum (AH) and Melilotus officinalis (MO) to inhibit the plasma coagulant, proteolytic and phospholipase A2 (PLA2) activities of Bothrops jararaca, B. jararacussu, and B. neuwiedi venoms, as well as chemical characterization. The extracts from AH and MO were incubated with each venom for 30 min at 37 oC and then activities were assessed. AH inhibited 38% and 55% of the proteolytic activity of B. jararaca and B. neuwiedi venoms, respectively and MO inhibited 70% of this activity; but they failed to inhibit B. jararacussu venom. AH and MO inhibited more efficiently the B. jararaca- and B. neuwiedi venom-induced coagulation. AH and MO inhibited 60% of PLA2 of B. jararaca, 30% of B. jararacussu and 40% of B. neuwiedi activities. Overall, AH and MO inhibited with more efficacy the activities of B. jararaca and B. neuwiedi venoms. The extracts contain flavonoids, saponins, rosmarinic acid, quercetin, and phenolic acids. Thus, the work provided potential of these plants to complement commercial antivenoms against envenomation by Bothrops species.