Hippocampal acetylcholinesterase activation induced by streptozotocin in mice is protected by an organotellurium compound without evidence of toxicity.

The cognitive deficit, which is like Alzheimer's disease and is associated with oxidative damage, may be induced by exposure to streptozotocin. This study aimed to evaluate if the tellurium-containing organocompound, 3j, 5'-arylchalcogeno-3-aminothymidine derivative, interferes with the effects of streptozotocin, as well as to investigate its toxicity in adult mice. Cognitive deficit was induced by two doses of streptozotocin (2.25 mg/kg/day, 48 h interval) intracerebroventricularly. After, the mice were subcutaneously treated with 3j (8.62 mg/kg/day) for 25 days. The effects were assessed by evaluating hippocampal and cortical acetylcholinesterase and behavioral tasks. 3j toxicity was investigated for 10 (0, 21.55, or 43.10 mg/kg/day) and 37 (0, 4.31, or 8.62 mg/kg/day) days by assessing biometric parameters and glucose and urea levels, and alanine aminotransferase activity in blood plasma. 3j exposure did not alter the behavioral alterations induced by streptozotocin exposure. On the other hand, 3j exposure normalized hippocampus acetylcholinesterase activity, which is enhanced by streptozotocin exposure. Toxicity evaluation showed that the administration of 3j for either 10 or 37 days did not cause harmful effects on the biometric and biochemical parameters analyzed. Therefore, 3j does not present any apparent toxicity and reverts acetylcholinesterase activity increase induced by streptozotocin in young adult mice.

Transcranial direct current stimulation to facilitate neurofunctional rehabilitation in children with autism spectrum disorder: a protocol for a randomized, sham-controlled, double-blind clinical trial.

Background: Anodal transcranial direct current stimulation (tDCS) over the primary motor cortex and cerebellum is gaining prominence in the literature due to its potential to favor learning and motor performance. If administered during motor training, tDCS is capable of increasing the effect of training. Considering the motor impairment presented by children with Autism Spectrum Disorders (ASD), atDCS applied during motor training may contribute to the rehabilitation of these children. However, it is necessary to examine and compare the effects of atDCS over the motor cortex and the cerebellum on the motor skills of children with ASD. This information may benefit future clinical indications of tDCS for rehabilitation of children with ASD. The aim of the proposed study is to determine whether anodal tDCS over the primary motor cortex and cerebellum can enhance the effects of gait training and postural control on motor skills, mobility, functional balance, cortical excitability, cognitive aspects and behavioral aspects in children with ASD. Our hypothesis is the active tDCS combined with motor training will enhance the performance of the participants in comparison to sham tDCS. Methods and design: A randomized, sham-controlled, double-blind clinical trial will be conducted involving 30 children with ASD that will be recruited to receive ten sessions of sham or ten sessions of active anodal tDCS (1 mA, 20 min) over the primary motor cortex or cerebellun combined with motor training. The participants will be assessed before as well as one, four and eight weeks after the interventions. The primary outcome will be gross and fine motor skills. The secondary outcomes will be mobility, functional balance, motor cortical excitability, cognitive aspects and behavioral aspects. Discussion: Although abnormalities in gait and balance are not primary characteristics of ASD, such abnormalities compromise independence and global functioning during the execution of routine activities of childhood. If demonstrated that anodal tDCS administered over areas of the brain involved in motor control, such as the primary motor cortex and cerebellum, can enhance the effects of gait and balance training in only ten sessions in two consecutive weeks, the clinical applicability of this stimulation modality will be expanded as well as more scientifically founded.Clinical trial registration February 16, 2023 (https://ensaiosclinicos.gov.br/rg/RBR-3bskhwf).

Biochemical Parameters of Female Wistar Rats and Their Offspring Exposed to Inorganic Mercury in Drinking Water during the Gestational and Lactational Periods.

The aim of this study was to investigate the effects of inorganic mercury (Hg2+) exposure on biochemical parameters of dams and their offspring exposed to metal in drinking water. Female Wistar rats were exposed to 0, 10, and 50 µg Hg2+/mL (as HgCl2) for 42 days corresponding to gestational (21 days) and lactational (21 days) periods. The offspring were sacrificed on postnatal days 10, 20, 30, and 40. Dams exposed to Hg2+ presented a decrease in water intake in gestation [total: F(2,19) = 15.84; p ≤ 0.0001; daily: F(2,21) = 12.71; p = 0.0002] and lactation [total: F(2,19) = 4.619; p = 0.024; daily: F(2,21) = 5.309; p = 0.0136] without alteration in food intake. Dams exposed to 50 µg Hg2+/mL had an increase in kidney total [F(2,21) = 8.081; p = 0.0025] and relative [F(2,21) = 14.11; p = 0.0001] weight without changes in biochemical markers of nephrotoxicity. Moreover, dams had an increase in hepatic [F(2,10) = 3.847; p = 0.0577] and renal [F(2,11) = 6.267; p = 0.0152] metallothionein content concomitantly with an increase in renal Hg levels after Hg2+ exposure. Regarding offspring, the exposure to Hg2+in utero and breast milk increased the relative liver [F(2,18) = 5.33; p = 0.0152] and kidney [F(2,18) = 3.819; p = 0.0415] weight only on the postnatal day 40. In conclusion, dams were able to handle the Hg2+ avoiding the classic Hg2+ toxic effects as well as protecting the offspring. We suggest that this protection is related to the hepatic and renal metallothionein content increase.

Impact of Pesticides on Cancer and Congenital Malformation: A Systematic Review.

Pesticide exposure has deleterious effects on human health and development; however, no review has been conducted on human exposure to pesticides and the risk of congenital malformations and cancer in the same cohort. We systematically reviewed the evidence for this relationship following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Four databases, namely, PubMed, Scopus, Cochrane Library, and BVS, were searched for studies deposited till July 2020 that examined the influence of pesticide exposure on congenital malformations and cancer outcomes in the same cohort. Seven studies were systematically included in this review. Among these, four were case-control studies, two were cross-sectional studies, and one was a longitudinal cohort study. The sources of contamination were food, water, or exposure during agricultural work. A link between the occurrence of cancer, congenital malformations, and exposure to pesticides was observed in most studies.

Toxic metals that interact with thiol groups and alteration in insect behavior.

Toxic metals, such as mercury (Hg), lead (Pb), cadmium (Cd), and copper (Cu), are widespread in the biosphere, and human activities have contributed to their continuous release into the ecosystems. Metal-induced toxicity has been extensively studied in mammals; however, the effects of these metals on insects' behavior have been explored to far lesser degree. As the main mechanism of toxicity, the cationic metals, explored in this review, have high affinity for thiol-containing molecules, disrupting the function of several proteins and low-molecular-weight thiol-containing molecules. Existing literature has corroborated that Hg, Pb, Cd, and Cu can disrupt locomotor and mating behaviors, but their effects on insects' memory and learning have yet to be fully characterized. Though field studies on metal-induced toxicity in insects are limited, results from Drosophila melanogaster as an experimental model suggest that insects living in contaminated environments can have behavioral foraging and reproductive deficits, which may cause population decline. In this review, we address the interaction between metals and endogenous thiol groups, with emphasis on alterations in insect behavior.

IQ alteration induced by lead in developed and underdeveloped/developing countries: A systematic review and a meta-analysis.

The aim of this study was to evaluate the effects of Pb exposure on full-scale IQ score in pediatric subjects. Following PRISMA guidelines, the data from January 2010 to April 2020 were systematically searched and collected on electronic databases (PubMed, Scopus, and Embase). The eligibility criteria included cross-sectional, cohort, and case-control studies that were published in English, from 2010 to 2020, that analyzed the blood Pb levels of pediatric subjects (0-19 years) and possible changes in the full-scale IQ score. In this study, 2174 scientific papers were collected from three electronic databases. From those, 726 were duplicates and 1421 were excluded because they did not meet the eligibility criteria, resulting in a total of 27 papers, from which, seven were used to perform the meta-analysis. The 27 scientific papers systematically selected for this study were separated by the country where the study was realized in developed and underdeveloped/developing countries. In the underdeveloped/developing countries the blood Pb levels are higher and showed a greater variation (1.30-11.66 µgPb/dL of blood) than in countries with higher development index (0.57-4.80 µgPb/dL of blood). The full-scale IQ score are inversely proportional to the blood Pb values, and it is possible to see that in the underdeveloped/developing countries the full-scale IQ score showed lower values and greater variation (59.2-111) compared to the individuals from developed countries (91.9-114.5). In conclusion, it was observed that blood Pb levels alter the full-scale IQ score. Thus, policies for the prevention of environmental contamination and the reduction of Pb exposure must be taken, mainly, in underdeveloped/developing countries.

Systematic review and single-centre toxicology study identified analgesics and benzodiazepines as the main causes of paediatric medication poisoning.

AIM: This study evaluated medication poisoning in paediatric patients through a systematic review and a retrospective documentary analysis in a Brazilian toxicological centre. METHODS: The data were systematically collected on PubMed, Scopus and SciELO databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We included epidemiologic and prevalence studies that were published in English or Portuguese from 2013 to 2017 and covered paediatric patients. The retrospective incidence study was carried out in a Brazilian toxicological centre and was a documentary analysis of paediatric medication poisoning cases from 2005 to 2015. RESULTS: The systematic review comprised 13 papers covering 895 206 poisoning cases from six different countries. The main agents of intoxication were analgesics and antihistamines. The eight papers that explored the reasons for the poisonings showed that 93% of those 762 863 cases were accidental. The Brazilian toxicological centre recorded 443 paediatric patients poisoned by medication such as benzodiazepines, analgesics and antibiotics and found that 63.2% were accidental. However, it agreed with the global findings in many other aspects. CONCLUSION: The systematic review showed a sustained number of paediatric medication toxicity cases worldwide and the key findings were broadly reflected by the retrospective study carried out in the Brazilian toxicological centre.

A brief review on the natural history, venomics and the medical importance of bushmaster (Lachesis) pit viper snakes.

Snakes of the genus Lachesis, commonly known as bushmasters, are the largest venomous snakes in the Americas. Because these snakes have their habitats in areas of remote forests they are difficult to find, and consequently there are few studies of Lachesis taxa in their natural ecosystems. Bushmasters are distributed in tropical forest areas of South and Central America. In Brazil they can be found in the Amazon Rainforest and the Atlantic Forest. Despite the low incidence of cases, laquetic envenoming causes severe permanent sequelae due to the high amount of inoculated venom. These accidents are characterized by local pain, hemorrhage and myonecrosis that can be confused with bothropic envenomings. However, victims of Lachesis bites develop symptoms characteristic of Lachesis envenoming, known as vagal syndrome. An important message of this bibliographic synthesis exercise is that, despite having the proteomic profiles of all the taxa of the genus available, very few structure-function correlation studies have been carried out. Therefore the motivation for this review was to fill a gap in the literature on the genus Lachesis, about which there is no recent review. Here we discuss data scattered in a number of original articles published in specialized journals, spanning the evolutionary history and extant phylogeographic distribution of the bushmasters, their venom composition and diet, as well as the pathophysiology of their bites to humans and the biological activities and possible biotechnological applicability of their venom toxins.

Transcriptomic and Proteomic Tools in the Study of Hg Toxicity: What Is Missing?

Mercury is a hazardous substance that has unique neurodevelopmental toxic effects in humans. However, the precise sequence of molecular events that culminate in Hg-induced neuropathology is still unknown. Though the omics studies have been generating an enormous amount of new data about Hg toxicity, our ability to interpret such a large quantity of information is still limited. In this opinion article, we will reinforce the necessity of new high throughput and accurate analytical proteomic methodologies, especially, thiol and selenol-proteome. Overall, we posit that improvements in thiol- and selenol-proteomic analyses will be pivotal in identifying the primary cellular targets of Hg. However, a better understanding of the complex cascades and molecular pathways involved in its toxicity will require extensive complementary studies in more complex systems.

Synthesis and biological evaluation of new antioxidant and antiproliferative chalcogenobiotin derivatives for bladder carcinoma treatment.

Approximately 90% of bladder carcinomas are of the urothelial carcinoma type, which are characterized by high rates of recurrence and predisposition to progress to invasive tumors, representing one of the most costly neoplasms for health systems. Intravesical chemotherapy is a standard for the treatment of non-invasive bladder cancer. However, chemotherapy is usually aggressive and cytotoxic, which increases the death rates caused by cancer. Heterocyclic compounds which exhibit favorable pharmacokinetic and pharmacodynamic properties may enhance drug affinity for a target protein by targeting the treatment. Thus, this work presents the synthesis, characterization, and in vitro biological evaluation of new antioxidant (inhibition of lipid peroxidation, scavenging of free radical DPPH, and thiol peroxidase-like activity) and antiproliferative chalcogenobiotin derivatives and tests them against bladder carcinoma 5637 cells. A prominent response was obtained for the selected compounds, with tellurium biotin derivatives displaying effective antioxidant and antiproliferative activity. The effective compounds also demonstrated no toxicity in in vitro or in vivo studies.

High level of methylmercury exposure causes persisted toxicity in Nauphoeta cinerea.

Methylmercury (MeHg+) is a neurotoxicant abundantly present in the environment. The long-term effects of MeHg+ have been investigated in rodents, yet data on the long-term or persisted toxicity of MeHg+ in invertebrates is scanty. Here, we examined the acute, intermediate, and chronic effects upon dietary administration of MeHg+ in nymphs of Nauphoeta cinerea. Besides, the potential reversibility of the toxic effects of MeHg+ after a detoxification period was evaluated. Nymphs were exposed to diets containing 0 (control), 2.5, 25, and 100 µg MeHg+/g of diet for 10, 30, and 90 days. Additional groups of nymphs were fed with the same dose of MeHg+ for 30 days and then were subjected to a detoxification period for 60 days. The nymphs exposed to 100 µg MeHg+/g succumbed to a high mortality rate, along with multiple biochemical (increase of reactive oxygen species production and glutathione S-transferase activity, as well as decrease in the acetylcholinesterase activity) and behavioral alterations. We observed delayed mortality rate and behavioral alterations in nymphs exposed to 100 µg MeHg+/g for 30 days and subsequently subjected to 60 days of detoxification. However, the biochemical alterations did not persist throughout the detoxification period. In conclusion, our results established the persistent toxic effect of MeHg+ even after a prolonged detoxification period and evidenced the use of N. cinerea as an alternative model to study the toxicity of MeHg+.

Penetrance of the TP53 R337H Mutation and Pediatric Adrenocortical Carcinoma Incidence Associated with Environmental Influences in a 12-Year Observational Cohort in Southern Brazil.

The TP53 R337H mutation is associated with increased incidence of pediatric adrenocortical tumor (ACT). The different environmental conditions where R337H carriers live have not been systematically analyzed. Here, the R337H frequencies, ACT incidences, and R337H penetrance for ACT were calculated using the 2006 cohort with 4165 R337H carriers living in Paraná state (PR) subregions. The effectiveness of a second surveillance for R337H probands selected from 42,438 tested newborns in PR (2016 cohort) was tested to detect early stage I tumor among educated families without periodical exams. Estimation of R337H frequencies and ACT incidence in Santa Catarina state (SC) used data from 50,115 tested newborns without surveillance, ACT cases from a SC hospital, and a public cancer registry. R337H carrier frequencies in the population were 0.245% (SC) and 0.306% (PR), and 87% and 95% in ACTs, respectively. The ACT incidence was calculated as ~6.4/million children younger than 10 years per year in PR (95% CI: 5.28; 7.65) and 4.15/million in SC (CI 95%: 2.95; 5.67). The ACT penetrance in PR for probands followed from birth to 12 years was 3.9%. R337H carriers living in an agricultural subregion (C1) had a lower risk of developing pediatric ACT than those living in industrial and large urban subregion (relative risk = 2.4). One small ACT (21g) without recurrence (1/112) was detected by the parents in the 2016 cohort. ACT incidence follows R337H frequency in each population, but remarkably environmental factors modify these rates.

Visceral Manipulation Decreases Pain, Increases Cervical Mobility and Electromyographic Activity of the Upper Trapezius Muscle in Non-Specific Neck Pain Subjects with Functional Dyspepsia: Two Case Reports.

BACKGROUND AND PURPOSE: The lack of clear knowledge about the etiology of nonspecific neck pain (NS-NP) strengthens the need for other mechanisms, still poorly described in the literature, to be investigated. Therefore, a quantitative analysis of two cases of NS-NP in subjects with functiona dyspepsia was conducted in order to verify the immediate and seven-day postintervention effects of visceral manipulation (VM) to the stomach and liver on neck pain, cervical range of motion (ROM), and electromyographic (EMG) activity of the upper trapezius muscle. CASE DESCRIPTION: Case A was an 18-year-old female with a complaint of nonspecific neck pain for one year, with reported pain on waking, momentary intermittent pain, and occasional symptoms of paresthesia in the upper limbs. Case B was a 25-year-old female with a complaint of cervical pain for one year, accompanied by pain in the unilateral temporomandibular joint, and medial thoracic region. Both cases presented functional dyspepsia. OUTCOMES: The results demonstrated (subjects A and B, respectively) a general increase in cervical ROM (range: 12.5% to 44.44%) and amplitude of the EMG signal (immediately postintervention: 57.62 and 20.78; post seven days: 53.54% and 18.83%), and an increase in muscle fiber conduction velocity immediately postintervention (4.44% and 7.44%) and a decrease seven days postintervention (25.25% and 21.18%). For pain, a decrease was observed immediately postintervention (23.07% and 76.92%) and seven days postintervention (100% for both subjects). DISCUSSION: A single VM provided important clinical improvement in neck pain, cervical spine range of motion, and EMG activity of the upper trapezius muscle, immediately and seven days postintervention in two NS-NP subjects with functional dyspepsia.

Evaluation of the masticatory muscle function, physiological sleep variables, and salivary parameters after electromechanical therapeutic approaches in adult patients with Down syndrome: a randomized controlled clinical trial.

BACKGROUND: There are many comorbidities associated with Down syndrome (DS), including obstructive sleep apnea (OSA) and masticatory muscle alteration. Muscular hypotonia, in particular, of the masticatory and oropharyngeal muscles is one of the main characteristics of individuals with DS, resulting in impairments of speech, swallowing, and mastication in these individuals. In addition, total or partial obstruction of the airways during sleep can occur due to pharyngeal hypotonia, leading to snoring and to OSA. This progressive respiratory disorder is associated with a high risk of morbidity and mortality in individuals with DS. The aim of this research is to assess the therapeutic effects of surface neuromuscular electrical stimulation (NMES), the mastication apparatus (MA), and a mandibular advancement oral appliance (OAm) with an embedded thermosensitive microchip on the functions of masticatory muscles (bilateral masseter and temporal muscles), physiological sleep variables, and salivary parameters in adult patients with DS. METHODS: The patients with DS will be randomly selected and divided into three groups (DS-NMES, DS-MA, and DS-OAm) with a minimum of 10 patients in each group. A thermosensitive microchip will be embedded in the OAm to record its compliance. The therapeutic effects on masticatory muscle function will be investigated through electromyography, a caliper, and a force-transducer device; the sleep variables, in turn, will be evaluated by means of polysomnography. The physicochemical and microbiological properties of the saliva will also be analyzed, including the salivary flow, viscosity, buffer capacity, cortisol levels (susceptibility to psychological and/or physical stress), and Pseudomonas aeruginosa levels (risk of aspiration pneumonia) in these patients. The methods determined for this study will be carried out prior to and after 2 months of the recommended therapies. DISCUSSION: The primary outcomes would be the improvement and/or reestablishment of the function of masticatory muscles and the physiological sleep variables in this target public since individuals with DS commonly present generalized muscular hypotonia and dysfunction of the oropharyngeal musculature. As a secondary outcome indicator, the impact of the applied therapies (NMES, MA, and OAm) on the salivary microbiological and physicochemical properties in DS individuals will also be assessed. Furthermore, the compliance of OAm usage will be measured through a thermosensitive microchip. TRIAL REGISTRATION: Registro Brasileiro de Ensaios Clínicos, RBR-3qp5np . Registered on 20 February 2018.

Methylmercury's chemistry: From the environment to the mammalian brain.

Methylmercury is a neurotoxicant that is found in fish and rice. MeHg's toxicity is mediated by blockage of -SH and -SeH groups of proteins. However, the identification of MeHg's targets is elusive. Here we focus on the chemistry of MeHg in the abiotic and biotic environment. The toxicological chemistry of MeHg is complex in metazoans, but at the atomic level it can be explained by exchange reactions of MeHg bound to -S(e)H with another free -S(e)H group (R1S(e)-HgMe + R2-S(e)H ↔ R1S(e)H + R2-S(e)-HgMe). This reaction was first studied by professor Rabenstein and here it is referred as the "Rabenstein's Reaction". The absorption, distribution, and excretion of MeHg in the environment and in the body of animals will be dictated by Rabenstein's reactions. The affinity of MeHg by thiol and selenol groups and the exchange of MeHg by Rabenstein's Reaction (which is a diffusion controlled reaction) dictates MeHg's neurotoxicity. However, it is important to emphasize that the MeHg exchange reaction velocity with different types of thiol- and selenol-containing proteins will also depend on protein-specific structural and thermodynamical factors. New experimental approaches and detailed studies about the Rabenstein's reaction between MeHg with low molecular mass thiol (LMM-SH) molecules (cysteine, GSH, acetyl-CoA, lipoate, homocysteine) with abundant high molecular mass thiol (HMM-SH) molecules (albumin, hemoglobin) and HMM-SeH (GPxs, Selenoprotein P, TrxR1-3) are needed. The study of MeHg migration from -S(e)-Hg- bonds to free -S(e)H groups (Rabenstein's Reaction) in pure chemical systems and neural cells (with special emphasis to the LMM-SH and HMM-S(e)H molecules cited above) will be critical to developing realistic constants to be used in silico models that will predict the distribution of MeHg in humans.

Pharmacological characterization of cnidarian extracts from the Caribbean Sea: evaluation of anti-snake venom and antitumor properties.

BACKGROUND: Cnidarians produce toxins, which are composed of different polypeptides that induce pharmacological effects of biotechnological interest, such as antitumor, antiophidic and anti-clotting activities. This study aimed to evaluate toxicological activities and potential as antitumor and antiophidic agents contained in total extracts from five cnidarians: Millepora alcicornis, Stichodactyla helianthus, Plexaura homomalla, Bartholomea annulata and Condylactis gigantea (total and body wall). METHODS: The cnidarian extracts were evaluated by electrophoresis and for their phospholipase, proteolytic, hemorrhagic, coagulant, fibrinogenolytic, neuromuscular blocking, muscle-damaging, edema-inducing and cytotoxic activities. RESULTS: All cnidarian extracts showed indirect hemolytic activity, but only S. helianthus induced direct hemolysis and neurotoxic effect. However, the hydrolysis of NBD-PC, a PLA2 substrate, was presented only by the C. gigantea (body wall) and S. helianthus. The extracts from P. homomalla and S. helianthus induced edema, while only C. gigantea and S. helianthus showed intensified myotoxic activity. The proteolytic activity upon casein and fibrinogen was presented mainly by B. annulata extract and all were unable to induce hemorrhage or fibrinogen coagulation. Cnidarian extracts were able to neutralize clotting induced by Bothrops jararacussu snake venom, except M. alcicornis. All cnidarian extracts were able to inhibit hemorrhagic activity induced by Bothrops moojeni venom. Only the C. gigantea (body wall) inhibited thrombin-induced coagulation. All cnidarian extracts showed antitumor effect against Jurkat cells, of which C. gigantea (body wall) and S. helianthus were the most active; however, only C. gigantea (body wall) and M. alcicornis were active against B16F10 cells. CONCLUSION: The cnidarian extracts analyzed showed relevant in vitro inhibitory potential over the activities induced by Bothrops venoms; these results may contribute to elucidate the possible mechanisms of interaction between cnidarian extracts and snake venoms.

Neurodevelopmental Effects of Mercury.

The toxicology of mercury (Hg) is of concern since this metal is ubiquitously distributed in the environment, and living organisms are routinely exposed to Hg at low to high levels. The toxic effects of Hg are well studied and it is known that they may differ depending on the Hg chemical species. In this chapter, we emphasize the neurotoxic effects of Hg during brain development. The immature brain is more susceptible to Hg exposure, since all the Hg chemical forms, not only the organic ones, can harm it. The possible consequences of Hg exposure during the early stages of development, the additive effects with other co-occurring neurotoxicants, and the known mechanisms of action and targets will be addressed in this chapter.

Pharmacological characterization of cnidarian extracts from the Caribbean Sea: evaluation of anti-snake venom and antitumor properties

Cnidarians produce toxins, which are composed of different polypeptides that induce pharmacological effects of biotechnological interest, such as antitumor, antiophidic and anti-clotting activities. This study aimed to evaluate toxicological activities and potential as antitumor and antiophidic agents contained in total extracts from five cnidarians: Millepora alcicornis, Stichodactyla helianthus, Plexaura homomalla, Bartholomea annulata and Condylactis gigantea (total and body wall). Methods: The cnidarian extracts were evaluated by electrophoresis and for their phospholipase, proteolytic, hemorrhagic, coagulant, fibrinogenolytic, neuromuscular blocking, muscle-damaging, edema-inducing and cytotoxic activities. Results: All cnidarian extracts showed indirect hemolytic activity, but only S. helianthus induced direct hemolysis and neurotoxic effect. However, the hydrolysis of NBD-PC, a PLA2 substrate, was presented only by the C gigantea (body wall) and S. helianthus. The extracts from P. homomalla and S. helianthus induced edema, while only C gigantea and S. helianthus showed intensified myotoxic activity. The proteolytic activity upon casein and fibrinogen was presented mainly by B. annulata extract and all were unable to induce hemorrhage or fibrinogen coagulation. Cnidarian extracts were able to neutralize clotting induced by Bothrops jararacussu snake venom, except M. alcicornis. All cnidarian extracts were able to inhibit hemorrhagic activity induced by Bothrops moojeni venom. Only the C. gigantea (body wall) inhibited thrombin-induced coagulation. All cnidarian extracts showed antitumor effect against Jurkat cells, of which C. gigantea (body wall) and S. helianthus were the most active; however, only C. gigantea (body wall) and M. alcicornis were active against B16F10 cells. Conclusion: The cnidarian extracts analyzed showed relevant in vitro inhibitory potential over the activities induced by Bothrops venoms; these results may contribute to elucidate the possible mechanisms of interaction between cnidarian extracts and snake venoms.(AU)

Pharmacological characterization of cnidarian extracts from the Caribbean Sea: evaluation of anti-snake venom and antitumor properties

Background: Cnidarians produce toxins, which are composed of different polypeptides that induce pharmacological effects of biotechnological interest, such as antitumor, antiophidic and anti-clotting activities. This study aimed to evaluate toxicological activities and potential as antitumor and antiophidic agents contained in total extracts from five cnidarians: Millepora alcicornis, Stichodactyla helianthus, Plexaura homomalla, Bartholomea annulata and Condylactis gigantea (total and body wall). Methods: The cnidarian extracts were evaluated by electrophoresis and for their phospholipase, proteolytic, hemorrhagic, coagulant, fibrinogenolytic, neuromuscular blocking, muscle-damaging, edema-inducing and cytotoxic activities. Results: All cnidarian extracts showed indirect hemolytic activity, but only S. helianthus induced direct hemolysis and neurotoxic effect. However, the hydrolysis of NBD-PC, a PLA2 substrate, was presented only by the C gigantea (body wall) and S. helianthus. The extracts from P. homomalla and S. helianthus induced edema, while only C gigantea and S. helianthus showed intensified myotoxic activity. The proteolytic activity upon casein and fibrinogen was presented mainly by B. annulata extract and all were unable to induce hemorrhage or fibrinogen coagulation. Cnidarian extracts were able to neutralize clotting induced by Bothrops jararacussu snake venom, except M. alcicornis. All cnidarian extracts were able to inhibit hemorrhagic activity induced by Bothrops moojeni venom. Only the C. gigantea (body wall) inhibited thrombin-induced coagulation. All cnidarian extracts showed antitumor effect against Jurkat cells, of which C. gigantea (body wall) and S. helianthus were the most active; however, only C. gigantea (body wall) and M. alcicornis were active against B16F10 cells...(AU)

Pharmacological characterization of cnidarian extracts from the Caribbean Sea: evaluation of anti-snake venom and antitumor properties

Background: Cnidarians produce toxins, which are composed of different polypeptides that induce pharmacological effects of biotechnological interest, such as antitumor, antiophidic and anti-clotting activities. This study aimed to evaluate toxicological activities and potential as antitumor and antiophidic agents contained in total extracts from five cnidarians: Millepora alcicornis, Stichodactyla helianthus, Plexaura homomalla, Bartholomea annulata and Condylactis gigantea (total and body wall). Methods: The cnidarian extracts were evaluated by electrophoresis and for their phospholipase, proteolytic, hemorrhagic, coagulant, fibrinogenolytic, neuromuscular blocking, muscle-damaging, edema-inducing and cytotoxic activities. Results: All cnidarian extracts showed indirect hemolytic activity, but only S. helianthus induced direct hemolysis and neurotoxic effect. However, the hydrolysis of NBD-PC, a PLA2 substrate, was presented only by the C gigantea (body wall) and S. helianthus. The extracts from P. homomalla and S. helianthus induced edema, while only C gigantea and S. helianthus showed intensified myotoxic activity. The proteolytic activity upon casein and fibrinogen was presented mainly by B. annulata extract and all were unable to induce hemorrhage or fibrinogen coagulation. Cnidarian extracts were able to neutralize clotting induced by Bothrops jararacussu snake venom, except M. alcicornis. All cnidarian extracts were able to inhibit hemorrhagic activity induced by Bothrops moojeni venom. Only the C. gigantea (body wall) inhibited thrombin-induced coagulation. All cnidarian extracts showed antitumor effect against Jurkat cells, of which C. gigantea (body wall) and S. helianthus were the most active; however, only C. gigantea (body wall) and M. alcicornis were active against B16F10 cells...