Acute renal failure is a common complication caused by Bothrops viper envenomation. In this study, the nefrotoxicity of a main component of B. leucurus venom called L-aminoacid oxidase (LAAO-Bl) was ...evaluated by using tubular epithelial cell lines MDCK and HK-2 and perfused kidney from rats. LAAO-Bl exhibited cytotoxicity, inducing apoptosis and necrosis in MDCK and HK-2 cell lines in a concentration-dependent manner. MDCK apoptosis induction was accompanied by Ca2+ release from the endoplasmic reticulum, reactive oxygen species (ROS) generation and mitochondrial dysfunction with enhanced expression of Bax protein levels. LAAO-Bl induced caspase-3 and caspase-7 activation in both cell lines. LAAO-Bl (10 μg/mL) exerts significant effects on the isolated kidney perfusion increasing perfusion pressure and urinary flow and decreasing the glomerular filtration rate and sodium, potassium and chloride tubular transport. Taken together our results suggest that LAAO-Bl is responsible for the nephrotoxicity observed in the envenomation by snakebites. Moreover, the cytotoxic of LAAO-Bl to renal epithelial cells might be responsible, at least in part, for the nephrotoxicity observed in isolated kidney.
The Spike protein (S protein) is a critical component in the infection of the new coronavirus (SARS-CoV-2). The objective of this work was to evaluate whether peptides from S protein could cause ...negative impact in the aquatic animals. The aquatic toxicity of SARS-CoV-2 Spike protein peptides derivatives has been evaluated in tadpoles (n = 50 tadpoles/5 replicates of 10 animals) from species Physalaemus cuvieri (Leptodactylidae). After synthesis, purification, and characterization of peptides (PSDP2001, PSDP2002, PSDP2003) an aquatic contamination has been simulated with these peptides during 24 h of exposure in two concentrations (100 and 500 ng/mL). The control group (“C”) was composed of tadpoles kept in polyethylene containers containing de-chlorinated water. Oxidative stress, antioxidant biomarkers and AChE activity were assessed. In both concentrations, PSPD2002 and PSPD2003 increased catalase and superoxide dismutase antioxidants enzymes activities, as well as oxidative stress (nitrite levels, hydrogen peroxide and reactive oxygen species). All three peptides also increased acetylcholinesterase activity in the highest concentration. These peptides showed molecular interactions in silico with acetylcholinesterase and antioxidant enzymes. Aquatic particle contamination of SARS-CoV-2 has cholinesterasic effect in P. cuvieri tadpoles. These findings indicate that the COVID-19 can constitute environmental impact or biological damage potential.
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•SARS-CoV-2 spike protein peptides (PSDP) were synthesized, purified, and characterized by solid phase peptide synthesis.•PSDP peptides promoted REDOX imbalance and acute neurotoxicity in tadpoles (Physalaemus cuvieri).•In silico studies have shown interactions between peptides and acetylcholinesterase and antioxidant enzymes.•Aquatic particle contamination of SARS-CoV-2 can constitute additional environmental damage.
Snake envenomation (Bothrops genus) is common in tropical countries and acute kidney injury is one of the complications observed in Bothrops snakebite with relevant morbidity and mortality. Here, we ...showed that Bothropoides pauloensis venom (BpV) decreased cell viability (IC50 of 7.5 μg/mL). Flow cytometry with annexin V and propidium iodide showed that cell death occurred predominantly by apoptosis and late apoptosis, through caspases 3 and 7 activation, mitochondrial membrane potential collapse and ROS overproduction. BpV reduced perfusion pressure, renal vascular resistance, urinary flow, glomerular filtration rate, percentage of sodium, chloride or potassium tubular transportation. These findings demonstrated that BpV cytotoxicity on renal epithelial cells might be responsible for the nephrotoxicity observed in isolated kidney.
•Bothropoides pauloensis venom induced apoptosis and necrosis in MDCK cells.•The venom induced caspases 3 and 7 activation, mitochondrial depolarization and ROS overproduction in MDCK cells.•B. pauloensis venom induced alterations in rat isolated kidney.
Cancer is indisputably one of the leading causes of death worldwide. Snake venoms are a potential source of bioactive compounds, complex mixtures constituted mainly of proteins and peptides with ...several pharmacological possibilities, including the potential to inhibit tumoral cell growth. In the present study, it was evaluated the antitumor effect of crude venom of Bothrops erythromelas (BeV), Bothrops jararaca (from Southern and Southeastern- BjsV and BjsdV, respectively) and Bothrops alternatus (BaV) in in vitro Chronic myeloid leukemia (CML) cancer cell line model. After 24 h of cell exposure to 10 and 50 μg/mL, BjsV, BjsdV, and BaV exerted a decrease in cell viability in both concentrations. BeV was not cytotoxic and, therefore wasn't chosen for further mechanism of action investigation. Furthermore, morphological alterations show modification typical of apoptosis. Also, was observes a significant cell cycle arrest in the S phase by BjsdV and BaV treatment. Flow cytometry evidenced the involvement of changes in the cell membrane permeability and the mitochondrial function by BjsV and BjsdV, corroborating with the triggering of the apoptotic pathway by the venom administration. BjsV, BjsdV, and BaV also led to extensive DNA damage and were shown to modulate the gene expression of transcripts related to the cell cycle progression and suppress the expression of the BCR-ABL1 oncogene. Altogether, these findings suggest that the venoms trigger the apoptosis pathway due to mitochondrial damage and cell cycle arrest, with modulation of intracellular pathways important for CML progression. Thus, indicating the pharmacological potential of these venoms in the development of new antitumoral compounds.
: Seaweeds have attracted special interest as good sources of sulphated polysaccharides (SP) for use in pharmaceutical industries and biotechnology. In this study, we evaluated the effects of SP ...from the red seaweed Gracilaria cornea (Gc‐TSP) in nociceptive and inflammatory models. In mice, Gc‐TSP (3, 9 or 27 mg/kg) significantly reduced nociceptive responses, as measured by the number of writhes, at all tested doses. In a formalin test, Gc‐TSP significantly reduced licking time in both phases of the test at a dose of 27 mg/kg. In a hot‐plate test, the antinociceptive effect was observed only in animals treated with 27 mg/kg of Gc‐TSP, suggesting that the analgesic effect occurs through a central action mechanism at the highest dose. Gc‐TSP (3, 9 or 27 mg/kg) caused only a slight reduction in neutrophil migration in the rat peritoneal cavity. However, lower doses of Gc‐TSP (3 and 9 mg/kg) significantly inhibited paw oedema induced by carrageenan, especially at 3 hr after treatment. Reduction in oedema was confirmed by myeloperoxidase activity in the affected paw tissue. In addition, treatment (s.c.) of animals with different doses of Gc‐TSP inhibited paw oedema induced by dextran within the first hour in all doses tested. After 14 consecutive days of intraperitoneal administration of Gc‐TSP (9 mg/kg), we measured the wet weight of the liver, kidney, heart, spleen and thymus and performed biochemical, haematological and histopathological evaluations. No systemic damage was found. These results indicate that Gc‐TSP possesses analgesic and anti‐inflammatory effects and is a potentially important tool worthy of further study.
Scorpion envenomation represents an important health problem in many parts of the world, due to the high number and severity of accidents. Recent studies demonstrated that some species can produce ...venoms with genetic damage potential. Here, we evaluated whether Tityus stigmurus venom causes genetic damage in blood and testicular cells of Swiss mice. We also analyzed the effect of the venom on the number of spermatogenic lineage cells. Five groups of mice received 0.387 mg/kg of the venom, intraperitoneally; one group received saline solution (control group). Blood and testicular cells were collected for comet assay and histological analysis at different times after treatment (1, 2, 6, 12, and 48 h). Blood was also collected 48 h after treatment for the micronucleus test in erythrocytes. Histological analysis was performed by counting cells of the spermatogenic lineages; the nuclear area of elongated spermatocytes was also evaluated. Treatment with the venom induced DNA damage that endured from 1 h to 48 h, as confirmed by the comet assay. The micronucleus test demonstrated that the venom induced mutations in erythrocytes. The number of spermatogonia and rounded spermatids decreased in some groups; the number of elongated spermatids increased, and their nuclear size decreased 1 h after treatment. Genetic damage can be caused directly by the venom, but we suggested that reactive oxygen species that result from inflammatory process caused by the envenomation may have an important role in the DNA damage. Genetic damage and apoptosis may explain the changes in the number of spermatogenic cells. Furthermore, the decrease in nuclear area may result from chromatin loss. Genetic damage in testicular cells, associated with alterations in the number and morphology of spermatogenic cells, can result in reproduction disorders in animals, or humans, stung by T. stigmurus.
•Tityus stigmurus venom induces DNA damage in blood and testicular cells of mice.•The venom also induces mutations in blood of mice as seen by micronucleus test.•Number and nuclear morphology of spermatogenic lineage is altered by the venom.•Tityus stigmurus sting may result in reproductive disorders in animals and humans.
Red and brown algae sulfated polysaccharides (SPs) have been widely investigated as antinociceptive and/or anti-inflammatory agents; however, no description of these biological properties concerning ...green algae SPs have been reported. Caulerpa curpressoides (Chlorophyta) presents three SPs fractions (Cc-SP1, Cc-SP2, and Cc-SP3). Anticoagulant (in vitro) and anti- and pro-thrombotic (in vivo) effects of Cc-SP2 had been recently reported. We evaluated the effects of Cc-SP2 using models of nociception and acute inflammation in vivo.
Male Swiss mice received Cc-SP2 (iv) 30 min prior to receiving 0.6% acetic acid (10 ml/kg, ip), 1% formalin (20 μl, sc) or were subjected to thermal stimuli (51 ± 1 °C). Cc-SP2 was injected sc to male Wistar rats in a peritonitis model or a paw edema model using carrageenan (ip or ipl, 500 μg). To analyze the systemic effects, Cc-SP2 (27 mg/kg, sc) was administrated to both genders mice before waiting for 14 days.
Cc-SP2 (3, 9 or 27 mg/kg) reduced (p < 0.05) the number of writhes induced by acetic acid by 57, 89.9 and 90.6%, respectively, the licking time in the first (9 or 27 mg/kg with 42.47 and 52.1%, respectively) and the second (3, 9 or 27 mg/kg with 68.95, 82.34 and 84.61%, respectively) phases. In the hot-plate test, the antinociceptive effect of Cc-SP2 (9 mg/kg) was primarily observed at 60 min (26.7 ± 1.2 s), with its effect reversed by naloxone (8.6 ± 1.3 s), suggesting the involvement of the opioid system. Cc-SP2 (3, 9 or 27 mg/kg, sc, p < 0.05) showed anti-inflammatory effects by decreasing neutrophils migration by 64, 69 and 73%, respectively, and potently reduced the paw edema, especially at the second (0.16 ± 0.02, 0.16 ± 0.03 and 0.12 ± 0.05 ml) and third (0.16 ± 0.03, 0.18 ± 0.02 and 0.14 ± 0.04 ml) hours, respectively. Cc-SP2 did not cause hepatic or renal alterations or affect body mass or the macroscopy of the organs examined (p > 0.05). Histopathological analyses of the liver and kidney showed that both organs were affected by Cc-SP2 treatment, but these effects were considered reversible.
The results indicate that the analgesic and anti-inflammatory effects of Cc-SP2 could be of biomedical applicability as a new, natural tool in pain and acute inflammatory conditions.
Snakebite envenomation is an important health problem in tropical countries, with severe human and social consequences. In Latin America, the Bothrops species constitute the main threat to humans, ...and the envenomation caused by these species quickly develops into severe local tissue damage, including swelling, hemorrhaging, myonecrosis, skin ulceration, and pain. The systemic effects of envenomation are usually neutralized by antivenom serum therapy, despite its intrinsic risks. However, neutralization of local tissue damage remains a challenge. To improve actual therapy, two major alternatives are proposed: the rational design of new specific antibodies for most of the tissue damaging/ poor immunogenic toxins, or the search for new synthetic or natural compounds which are able to inhibit these toxins and complement the serum therapy. Natural compounds isolated from plants, mainly from those used in folk medicine to treat snakebite, are a good choice for finding new lead compounds to improve snakebite treatment and minimize its consequences for the victims. In this article, we reviewed the most promising plants and phytocompounds active against bothropic venoms.
Sulfated polysaccharides from red marine algae have presented a variety of potentially therapeutic biological effects, however, their antinocicpetive and anti-inflammatory properties are not well ...understood.
Male Swiss mice were pretreated with a sulfated polysaccharidic fraction obtained from the marine alga Acanthophora muscoides (AmII) (1, 3 or 9 mg/kg, iv) 30 min prior to either receiving an injection of 0.8% acetic acid or 1% formalin or prior to a thermal stimulus. AmII (1, 3 or 9 mg/kg, sc) was evaluated on carrageenan-, dextran- bradykinin-, histamine- and serotonin-induced rat paw edema models. AmII (500 μg, sc) was also injected into the paw. Additionally, mice were treated with the total sulfated polysaccharides from A. muscoides (Am-TSP) (20 mg/kg, ip) for 14 days.
AmII reduced the number of acetic acid-induced writhes and licking time in the second phase of the formalin test, but it did not alter the response latency in the hot plate test, suggesting that its antinociceptive action occurs through a peripheral mechanism. AmII did not reduce carrageenan-induced paw edema and MPO activity. However, it reduced dextran-, histamine- and serotonin-induced paw edemas, but not bradykinin-induced edema, suggesting that histamine is the major target of AmII anti-edematogenic activity. AmII injected into the paw did not evoke local edema. Furthermore, Am-TSP induced no consistent signs of systemic damage, as revealed by body mass, organs wet weight and by biochemical, hematological and histopathological analyses.
AmII has important antinociceptive and anti-inflammatory properties and represents an important therapeutic agent warranting future studies.
Scorpions belonging to the Tityus genus are of medical interest in Brazil. Among them, Tityus stigmurus is the main scorpion responsible for stings in the Northeast region. After a sting, the ...scorpion venom distributes rapidly to the organs, reaching the kidneys quickly. However, there are few studies concerning the renal pathophysiology of scorpion poisoning. In this study, we evaluated the effects of T. stigmurus venom (TsV) on renal parameters in isolated rat kidneys. Wistar rats (n = 6), weighing 250-300 g, were perfused with Krebs-Henseleit solution containing 6 g/100 mL bovine serum albumin. TsV at 0.3 and 1.0 μg/mL was tested, and the effects on perfusion pressure (PP), renal vascular resistance (RVR), urinary flow (UF), glomerular filtration rate (GFR), and electrolyte excretion were analyzed. Effects were observed only at TsV concentration of 1.0 μg/mL, which increased PP (controlPP40' = 92.7 ± 1.95; TsVPP40' = 182.0 ± 4.70* mmHg, *p < 0.05), RVR (controlRVR40' = 3.28 ± 0.23 mmHg; TstRVR40' = 6.76 ± 0.45* mmHg, *p < 0.05), UF (controlUF50' = 0.16 ± 0.04; TstUF50' = 0.60 ± 0.10* mL/g/min,*p < 0.05), GFR and electrolyte excretion, with histological changes that indicate renal tubular injury. In conclusion, T. stigmurus venom induces a transient increase in PP with tubular injury, both of which lead to an augmented electrolyte excretion.
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