Effects of Tityus serrulatus scorpion venom on thromboelastogram in rats.

Thromboelastometry was used to evaluate blood coagulation in anesthetized rats after intravenous administration of Tityus serrulatus scorpion venom (Tx). Tracheostomy followed by catheterization of the left jugular vein and right carotid artery were performed for Tx or Ringer's lactate solution injection and blood sample harvesting, respectively. Blood samples were obtained at the beginning of the experiments (baseline) and at two, five, 15, 30, and 60 min after intoxication. The following coagulation parameters were analyzed: CT (Clotting Time), CFT (Clotting Formation Time), Alpha Angle (α), MCF (Maximum Clot Firmness) and TPI (Thrombodynamic Potential Index). Toxin-induced hypercoagulability was demonstrated at the 15 and 60 min. We hypothesize Tx-induced hypercoagulability and enhanced clot formation could be explained by catecholamine release, systemic inflammatory response, and complement system activation, at least in the first hour after envenomation. Further studies are needed to determine the molecular mechanism of Tx-induced coagulopathy.

Malnutrition alters the cardiovascular responses induced by central injection of tityustoxin in Fischer rats.

Scorpion envenoming and malnutrition are considered two important public health problems in Brazil, involving mainly children. Both these conditions are more common among the economically stratified lower income portion of the population, thus suggesting that these factors should be analyzed concomitantly. It is known that cardiorespiratory manifestations, as cardiac arrhythmias, arterial hypertension and hypotension, pulmonary edema and circulatory failure are the main "causa mortis" of scorpion envenomation. Additionally, there are evidences in the literature that deficiencies in dietary intake endanger the CNS and modify the cardiovascular homeostasis. Then, the objective of this work is to evaluate the protein malnourished effect on cardiovascular responses induced by tityustoxin (TsTX, an α-type toxin extracted from the Tityus serrulatus scorpion venom). Fischer rats (n = 20) were injected i.c.v. with TsTX and divided in control and malnorished groups, which were, respectively, submitted to a control and a low-protein diet. Arterial pressure recordings were done until death of the animals. Although both groups presented an increased mean arterial pressure after TsTX injection, this increase was smaller and delayed in malnourished rats, when compared to control rats. In addition, heart rate increased only in rats from the control group. Finally, malnourished rats had an increase in survival time (9:9/13.5 vs. 15.5:10.5/18 min; p = 0.0009). In summary, our results suggest that the protein restriction attenuates the cardiovascular manifestations resulting from TsTX action on CNS.

Malnutrition during central nervous system growth and development impairs permanently the subcortical auditory pathway.

The brain that grows and develops under the continued influence of malnutrition presents permanent impairment on functioning and neurotransmitter release. The aim of this study was to investigate the chronic effects of neonatal food restriction on neurochemical and neurodynamical aspects within the primary auditory sensory pathway. Our working hypothesis is that neonatal malnutrition may affect the flow of primary sensory information both at a neurochemical and neurodynamical level. To test this hypothesis, three groups of rats were assigned, from birth to 370 days of life, to the following dietary scheme: a well-nourished (WN) group fed ad libitum lab chow diet; an undernourished (UN) group fed 60% of diet consumed by WN group; and a rehabilitated group, undergoing same dietary restriction as undernourished until 42 days of age and thereafter fed ad libitum until the end of the experiment. At 370 days of age, the animals were submitted to brainstem auditory-evoked potentials (BAEPs) recordings and sacrificed for neurochemical evaluation of glutamate release. Undernutrition decreased glutamate release in the cortex, hippocampus, midbrain and brainstem, and significantly increased the latency of BAEP wave V. In addition; the re-establishment of the dietary conditions was not sufficient to reverse the neurochemical and electrophysiological alterations observed in the UN group. Taken altogether, our results suggest that malnutrition imposed at a critical development period caused an irreversible effect within the auditory primary sensory pathway.

Chronic coffee and caffeine ingestion effects on the cognitive function and antioxidant system of rat brains.

Coffee is a popular beverage consumed worldwide and its effect on health protection has been well studied throughout literature. This study investigates the effect of chronic coffee and caffeine ingestion on cognitive behavior and the antioxidant system of rat brains. The paradigms of open field and object recognition were used to assess locomotor and exploratory activities, as well as learning and memory. The antioxidant system was evaluated by determining the activities of glutathione reductase (GR), glutathione peroxidase (GPx) and superoxide dismutase (SOD), as well as the lipid peroxidation and reduced glutathione content. Five groups of male rats were fed for approximately 80 days with different diets: control diet (CD), fed a control diet; 3% coffee diet (3%Co) and 6% coffee diet (6%Co), both fed a diet containing brewed coffee; 0.04% caffeine diet (0.04%Ca) and 0.08% caffeine diet (0.08%Ca), both fed a control diet supplemented with caffeine. The estimated caffeine intake was approximately 20 and 40 mg/kg per day, for the 3%Co-0.04%Ca and 6%Co-0.08%Ca treatments, respectively. At 90 days of life, the animals were subjected to the behavioral tasks and then sacrificed. The results indicated that the intake of coffee, similar to caffeine, improved long-term memory when tested with object recognition; however, this was not accompanied by an increase in locomotor and exploratory activities. In addition, chronic coffee and caffeine ingestion reduced the lipid peroxidation of brain membranes and increased the concentration of reduced-glutathione. The activities of the GR and SOD were similarly increased, but no change in GPx activity could be observed. Thus, besides improving cognitive function, our data show that chronic coffee consumption modulates the endogenous antioxidant system in the brain. Therefore, chronic coffee ingestion, through the protection of the antioxidant system, may play an important role in preventing age-associated decline in the cognitive function.

Effects induced by Apis mellifera venom and its components in experimental models of nociceptive and inflammatory pain.

The effects induced by Apis mellifera venom (AMV), melittin-free AMV, fraction with molecular mass < 10 kDa (F<10) or melittin in nociceptive and inflammatory pain models in mice were investigated. Subcutaneous administration of AMV (2, 4 or 6 mg/kg) or melittin-free AMV (1, 2 or 4 mg/kg) into the dorsum of mice inhibited both phases of formaldehyde-induced nociception. However, F<10 (2, 4 or 6 mg/kg) or melittin (2 or 3 mg/kg) inhibited only the second phase. AMV (4 or 6 mg/kg), but not F<10, melittin-free AMV or melittin, induced antinociception in the hot-plate model. Paw injection of AMV (0.05 or 0.10 mg), F<10 (0.05 or 0.1 mg) or melittin (0.025 or 0.050 mg) induced a nociceptive response. In spite of inducing nociception after paw injection, scorpion (Tityus serrulatus) or snake (Bothrops jararaca) venom injected into the dorsum of mice did not inhibit formaldehyde-induced nociception. In addition, AMV (6 mg/kg), but not F<10 (6 mg/kg) or melittin (3 mg/kg), inhibited formaldehyde paw oedema. Concluding, AMV, F<10 and melittin induce two contrasting effects: nociception and antinociception. AMV antinociception involves the action of different components and does not result from non-specific activation of endogenous antinociceptive mechanisms activated by exposure to noxious stimuli.

Effect of coffee on chemical hepatocarcinogenesis in rats.

The aim of this study was to investigate the effect of daily coffee ingestion on hepatocarcinogenesis in rats submitted to the resistant hepatocyte (RH) model. During lactation, the dams were fed a control or a coffee-supplemented diet. After weaning, male pups followed the same dietary protocol and were submitted to the RH model. The animals were sacrificed at 110 days of life. Removal of the medial and left lateral lobes was used as mitogenic stimulus, and the liver regeneration was estimated. Morphometric analyses of preneoplastic lesions were carried out on liver histological sections submitted to the histochemical procedure of the glucose-6-phosphatase activity. The gamma-glutamyltranspeptidase (GGT) activity was analyzed in the homogenate of regenerated livers. Body weight, mass liver regeneration, and hepatic cell architecture were not affected by coffee ingestion. In the group of animals fed the coffee-supplemented diet, the number of persistent and remodeling nodules was reduced (85.5% and 70.5%, respectively). The hepatic area occupied by the persistent nodules was also reduced (92%). There was a reduction of 7.7% in the GGT activity in the group fed the coffee-supplemented diet, although not statistically significant. The results indicate that coffee modulates chemical hepatocarcinogenesis in rats.

Electroencephalographic evidence of brainstem recruitment during scorpion envenomation.

Scorpion envenomation is a public health problem in Brazil, with most severe cases occuring in children under the age of 5 years (0.6% lethality). In fact, the toxic fractions of the Tityus serrulatus scorpion venom (TSSV) have greater permeability across the BBB of weanling rats when compared to adults. Although EEG alterations have been reported in up to 75% of pediatric severe cases, the role of the CNS in envenomation morbidity is still in debate. Our working hypothesis is that the neural substrates that play a major role in morbidity generate activity undetectable from EEG scalp leads. Twenty one-day-old rats (n=18) were injected s.c. with the deadliest toxic fraction of the TSSV, tityustoxin (TsTX; 2xDL50=6 mg/kg). EEG leads were stereotaxicaly implanted in the nucleus of the solitary tract (NTS) and left parietal cortex. EEG and ECG were continuously monitored by a video EEG system until death or for a maximum period of 240 min. An experimental group pre-treated with carbamazepine (CBZ) was added in order to better access the cause-effect relationship between neural discharges and the systemic ECG alterations. High amplitude discharges in the NTS, which correlated to cardiac alterations, were recorded soon after administration of TsTX. Abnormal electrographic activity spread throughout the cortex only later in the recording. As expected, the CBZ treatment increased the latency for the first epileptiform discharge, decreased EEG/ECG alterations and increased the general survival time. In summary: peripheral scorpion toxin inoculation recruits brainstem involved in cardiovascular control and initial electrographic activity was undetectable from the cortical electrode.

Carbamazepine is effective in the treatment of 21-day-old Wistar rats injected with Tityus serrulatus crude venom.

The scorpion-envenoming syndrome has an incidence of approximately 8000 accidents/year in Brazil; with most severe cases occurring during childhood and elderly. Previous results from our laboratory suggest that the effects of scorpion toxins on the central nervous system play a major role on the lethality induced by scorpion envenoming. Our group has shown that the pre-treatment with carbamazepine (CBZ) is able to increase the latency-to-death in developing animals inoculated with tityustoxin, a toxic fraction of the Tityus serrulatus crude venom. Nevertheless, in order to perceive CBZ as potentially useful in clinical practice, the efficiency of CBZ against crude venom inoculation and the pharmacological treatment introduced after envenomation must be addressed. Thus, the objective of this work was to evaluate CBZ therapeutic efficiency against scorpion envenomation in developing rats. Animals were treated with i.p. injections of either vehicle or CBZ (50 mg/kg or 100 mg/kg) 10 min after injected with a s.c. fixed volume of either saline or crude T. serrulatus venom extract (48 mg/kg). The dose chosen for venom inoculation was 16 times its DL50 for 21-day-old Wistar rats, invariably inducing death within 2 h. Although CBZ did not significantly reduce the pulmonary edema, it was effective in increasing survival rate by approximately 75% in treated rats. In conclusion, CBZ was effective in the treatment of T. serrulatus envenomation even though not blocking the pulmonary edema.

Dose-dependent effect of carbamazepine on weanling rats submitted to subcutaneous injection of tityustoxin.

The scorpion envenoming syndrome is a serious public health matter in Brazil. The most severe cases occur during childhood and elderly. Previous results from our laboratory suggest that the effects of scorpion toxins on the central nervous system play a major role on the lethality induced by scorpion envenoming. The aim of this work is to evaluate the therapeutic potential of carbamazepine (CBZ) injected i.p. 90 min before s.c. tityustoxin (TsTX) injection in weanling rats. Rats were divided into six experimental groups according to s.c. injection (saline or TsTX) and i.p. treatment (vehicle or CBZ 12, 50 and 100 mg/kg): Sal/Veh group (n=4); Sal/CBZ100 (n=4); TsTX/CBZ12 (n=6); TsTX/CBZ50 (n=8); TsTX/CBZ100 (n=8) and, at last, TsTX/Veh (n=8). The dose of TsTX was the same for all groups: 6.0mg/kg, twice the DL50 for weanling rats. Video images were recorded until death or for a maximum period of 240 min. Lungs were excised and weighed to evaluate edema. The results showed that CBZ (12, 50 and 100mg/kg) was able to increase the survival rate and latency-to-death of the rats. Only the group treated with 100mg/kg of CBZ had a decrease in the pulmonary edema. The known effect of CBZ reducing neuronal excitability most likely protected the neural substrates targeted by TsTX. Although treatment was performed before TsTX inoculation, the results are promising regarding CBZ as a therapeutic coadjuvant in the treatment of scorpion poisoning. The pharmacokinetics of CBZ can be very much improved by either changing the form of administration or encapsulating the drug in order to enhance solubility.

Carbamazepine protects the CNS of Wistar rats against the central effects of scorpion envenomation.

The scorpion envenoming syndrome is a serious public health matter in Brazil. Previous results from our laboratory suggest that the effects of scorpion toxins on the central nervous system play a major role on the lethality induced by scorpion envenoming. The objective of this work is to evaluate carbamazepine (CBZ) as a potential therapeutic agent against tityustoxin (TsTX) envenomation. The choice of i.c.v. toxin injection assures that TsTX is readily available in the parenchyma, configuring a worst case scenario for protecting the CNS afflicted by envenomation. Adult Wistar rats were submitted to surgery for guide cannulae (lateral ventricle) and electrodes (EEG-parietal cortices and ECG-thoracic leads) implantation. Animals (n=25) were treated with i.p. injections of either vehicle or CBZ 90 min before injected i.c.v. with a fixed volume of either saline or TsTX: vehicle treated/TsTX injected (1.74 microg, i.c.v.; n=4), CBZ treated (50mg/kg, i.p.)/TsTX injected (n=12); CBZ treated/saline injected (n=5); and vehicle treated/saline injected (n=4). Video EEG/ECG was recorded until death or for a maximum period of 90 min. Lungs were excised and weighed to evaluate edema. The results showed that 10 out of 12 CBZ treated rats survived to TsTX i.c.v. microinjection. CBZ significantly decreased cardiac arrhythmias and pulmonary edema in rats injected with TsTX. Furthermore, CBZ also significantly increased the latency for the first cortical epileptiform discharge. The known effect of CBZ reducing neuronal excitability most likely protected the neural substrates targeted by TsTX. CBZ was efficient in attenuating envenoming symptoms after the i.c.v. inoculation of the TsTX in rats. Thus, CBZ can be proposed as a therapeutic coadjuvant in the treatment of scorpion poisoning.

Curcuma longa ingestion protects in vitro hepatocyte membrane peroxidation

The goal of the present study was to evaluate the effect of turmeric ingestion on lipid peroxidation and GSH content, promoted by in vitro acetaminophen, on hepatocytes primary culture from well-nourished and malnourished rats. Four groups of Holtzman male rats were used: 1) WNG, well-nourished, fed lab chow diet ad libitum; 2) MNG, malnourished, fed 60 percent of the diet consumed by WNG; 3) WNG+T fed the same diet of WNG, but containing 1 percent of turmeric; 4) MNG+T fed 60 percent of the diet consumed by WNG+T. The animals were sacrificed at 90 days of age, the livers excised and hepatocytes primary cultures were prepared. Half of the plates of hepatocytes culture were treated with acetaminophen. Dose-response curve showed that 6 mM acetaminophen increased peroxidation around 54 percent and decreased GSH content around 63 percent. The model of malnutrition used, by restricting food ingestion (40 percent), decreased body weight in 33 percent and peroxidation index around 42 percent and increased GSH content around 43 percent. Turmeric ingestion decreased hepatocyte peroxidation in both well-nourished (42 percent) and malnourished rats (33 percent) and was able to avoid the acetaminophen pro-oxidant effect in both well-nourished and malnourished animals. Turmeric ingestion played a beneficial role to the organism and, therefore, can be considered a functional food.

O objetivo do presente estudo foi avaliar o efeito da ingestão de cúrcuma sobre a peroxidação lipídica e conteúdo de GSH, por ação tóxica in vitro de paracetamol, utilizando cultura primária de hepatócitos. Quatro grupos de ratos Holtzman foram usados: 1) GNN, normonutrido, alimentado ad libitum com ração de laboratório; 2) GDN, desnutrido, alimentado com 60 por cento da quantidade de ração consumida por GNN; 3) GNN+C, alimentado como GNN, mas contendo 1 por cento de cúrcuma na dieta; 4) GDN+C, alimentado como GDN, mas contendo 1 por cento de cúrcuma na dieta. Os animais foram sacrificados aos 90 dias de vida, e cultura de hepatócitos preparada. Metade das placas de cultura foi tratada com paracetamol. A curva dose-resposta mostrou que 6 mM de paracetamol aumentou em 54 por cento a peroxidação e diminuiu em 63 por cento o conteúdo de GSH. A restrição na ingestão de alimentos (40 por cento) diminuiu o peso corporal (33 por cento) ao sacrifício e o índice de peroxidação cerca de 42 por cento, entretanto, aumentou o conteúdo de GSH cerca de 43 por cento. A ingestão de cúrcuma diminuiu a peroxidação em ambos ratos normonutridos (42 por cento) e desnutridos (33 por cento) e evitou o efeito pro-oxidante de paracetamol em ambos os grupos. A cúrcuma exerceu efeito protetor antioxidante sobre o organismo.

Effect of acid secretion blockade on acute gastric mucosal lesions induced by Tityus serrulatus scorpion toxin in anaesthetized rats.

Scorpion venom (TX) promotes gastric acid and pepsin secretion leading to acute gastric mucosal lesions (AGML), when injected in animals. The goal of the present study was to observe the effects of acid gastric secretion blockers over the incidence of TX-induced AGML in vivo. To verify this model, we used male albino rats, fasted 18-20 h (n=122) and anaesthetized with urethane (1.4 g/kg, i.p.). Their trachea and left femoral vein were both cannulated; the first to avoid airway obstructions during scorpion intoxication and the second for administration of saline, TX and acid blockers. Following the surgical procedure, the animals were divided in 10 groups of at least 10 animals each. Control groups were injected with NaCl 0.9% 1 ml/kg (n=10) or TX 375 microg/kg (n=32). Test groups (n=10, each) received atropine 5 mg/kg, cimetidine 10mg/kg, ranitidine 2.5mg/kg, ranitidine 5mg/kg, omeprazol 1 mg/kg, omeprazol 4 mg/kg, octreotide 80 and octreotide 100 microg/kg 10 min before the TX was injected. After 1h of intoxication, the stomach was resected for macroscopic study and the gastric secretion was collected for volume, pH and acid output assessment. We observed that all blockers were able to completely or partially prevent the TX-induced acid secretion as well as the AGML (p<0.05). Our data suggest the TX-induced AGML can be prevented by different class of acid blockers injected before the intoxication.

Pharmacological investigation of the nociceptive response and edema induced by venom of the scorpion Tityus serrulatus.

In this study we characterized the nociceptive response and edema induced by the venom of the scorpion Tityus serrulatus in rats and mice and carried out a preliminary pharmacological investigation of the mechanisms involved in these responses. Intraplantar injection of the venom (1 or 10mug) induced edema and a marked ipsilateral nociceptive response, characterized by thermal and mechanical allodynia and paw licking behaviour. The nociceptive response was inhibited by previous intraperitoneal administration of indomethacin (4mg/kg), dipyrone (200mg/kg), cyproheptadine (10mg/kg) or morphine (5 or 10mg/kg), but not by dexamethasone (1 or 4mg/kg) or promethazine (1 or 5mg/kg). The edema was inhibited by previous treatment with promethazine (5 or 10mg/kg) or cyproheptadine (5 or 10mg/kg), but not by indomethacin (2 or 4mg/kg), dexamethasone (1 or 4mg/kg) or cromolyn (40 or 80mg/kg). Some bioactive amines, including histamine and 5-hydroxytryptamine, were found in the venom in low concentrations. In conclusion, the nociceptive response and edema induced by the venom of T. serrulatus may result from the action of multiple mediators including eicosanoids, histamine and 5-hydroxytryptamine. These results may lead to a better understanding of the host response to potent animal toxins and also give insights into a more rational pharmacological approach to alleviate the intense pain associated with the scorpion envenomation.

Ligation of the abdominal esophagus decreases scorpion toxin-induced gastric secretion in rats

PURPOSE: Scorpion toxin purified from Tityus serrulatus venom (Tx) induces an increase in volume, acidity and pepsin secretion in the gastric juice of rats. Ligation of oesophagus has been shown to reduce the acid gastric secretion in rats. The aim of this paper was to determine the influence of the esophageal ligation on gastric secretion induced by Tx in rats. METHODS: Forty-four male albino rats were given water ad libitum, but no food for 20 to 24 hours, anesthetized with urethane and the trachea and jugular vein cannulated. Cervical or abdominal esophageal ligation or sham-operations were performed before and after the injection of 0.25 mg/kg of scorpion toxin (fraction Tl) into the jugular vein. One hour later, the volume, acidity, pH and peptic activity of gastric juice were determined. RESULTS: The scorpion toxin induced an increase in gastric juice volume, acidity and pepsin output and a decrease in pH when injected into the vein of intact animals or in sham-operated animals. Cervical esophagus ligation did not interfere with the effects of toxin, however, ligation of the abdominal esophageal decreased the toxin effect on the rat stomach. CONCLUSION: Ligation of the abdominal esophagus decreases the gastric secretion induced by scorpion toxin.

Effects of alpha-scorpion toxin, tityustoxin on the release of [3H] dopamine of rat brain prefrontal cortical slices.

The effect of tityustoxin (TsTX) on the release of [3H] dopamine in rat brain prefrontal cortical slices was investigated. The stimulatory effect of TsTX was dependent on incubation time and TsTX concentration with an EC50 of 0.05 microM. The release of [3H] dopamine stimulated by TsTX is dependent of Na+ channels and thus, was completely, inhibited by tetrodotoxin. Tityustoxin-induced release of [3H] dopamine was not blocked by ethylene glycol-bis(beta-aminoethyl) ether (EGTA) and thus was independent of extracellular calcium. However, [3H] dopamine release induced by TsTX was inhibited by 52% by BAPTA, a calcium chelator. Moreover, dantrolene (100 microM) and tetracaine (500 microM) partially inhibited by 38 and 29%, respectively, the tityustoxin-induced release of [3H] dopamine from prefrontal cortical slices suggesting a role from intracellular calcium increase. In conclusion, part of the TsTX-induced release [3H] dopamine may be due to an effect of the toxin on the reversal of the dopamine transporter (DAT), but the majority of the toxin stimulated release of [3H] dopamine involves the mobilization of intracellular calcium stores.

Ligation of the abdominal esophagus decreases scorpion toxin-induced gastric secretion in rats

PURPOSE: Scorpion toxin purified from Tityus serrulatus venom (Tx) induces an increase in volume, acidity and pepsin secretion in the gastric juice of rats. Ligation of oesophagus has been shown to reduce the acid gastric secretion in rats. The aim of this paper was to determine the influence of the esophageal ligation on gastric secretion induced by Tx in rats METHODS: Forty-four male albino rats were given water ad libitum, but no food for 20 to 24 hours, anesthetized with urethane and the trachea and jugular vein cannulated. Cervical or abdominal esophageal ligation or sham-operations were performed before and after the injection of 0.25 mg/kg of scorpion toxin (fraction T1) into the jugular vein. One hour later, the volume, acidity, pH and peptic activity of gastric juice were determined. RESULTS: The scorpion toxin induced an increase in gastric juice volume, acidity and pepsin output and a decrease in pH when injected into the vein of intact animals or in sham-operated animals. Cervical esophagus ligation did not interfere with the effects of toxin, however, ligation of the abdominal esophageal decreased the toxin effect on the rat stomach. CONCLUSION: Ligation of the abdominal esophagus decreases the gastric secretion induced by scorpion toxin.

OBJETIVO: A toxina de escorpião purificada do veneno do escorpião Tityus serrulatus (Tx) induz um aumento no volume, acidez e secreção de pepsina no suco gástrico de ratos. A ligadura do esôfago diminui a secreção ácida do estômago em ratos. O objetivo deste trabalho foi determinar a influência da ligadura do esôfago sobre a secreção gástrica induzida pela Tx em ratos. MÉTODOS: 44 ratos machos, brancos foram administrados água ad libitum, mas não alimentados por 20 a 24 horas, anestesiados com uretana e canulados a traquéia e a veia jugular. Foram realizadas as ligaduras do esôfago cervical ou abdominal ou operações simuladas antes e após a administração na veia jugular de 0,25 mg/kg de toxina de escorpião (fração T1). Uma hora após foram determinados o volume, acidez, pH e atividade péptica do suco gástrico. RESULTADOS: A toxina de escorpião induziu um aumento do volume do suco gástrico, da acidez gástrica e da produção de pepsina e uma diminuição do pH quando injetada na veia de animais não operados ou com operação simulada. A ligadura do esôfago cervical não interferiu nos efeitos da toxina, enquanto a ligadura do esôfago abdominal diminuiu os efeitos da toxina no estômago do rato. CONCLUSÃO: A ligadura do esôfago abdominal diminui a secreção gástrica estimulada pela toxina de escorpião.

Effect of age on body distribution of Tityustoxin from Tityus serrulatus scorpion venom in rats.

Previous research from our Laboratory has shown a greater susceptibility of young animals, when compared to adults, to envenomation by tityustoxin (TsTX), one of the main toxins from Tityus serrulatus scorpion venom. Our hypothesis is that a differential body distribution of TsTX among adult and young animals could account for the worse prognosis of scorpion envenomation in infants. Thus, TsTX labeled with technetium-99m was injected (6 microg, subcutaneous) in adult (150-160 day-old) and young (21-22 day-old) male rats. Groups of animals were sacrificed at different times after TsTX injection (0.08, 1.0, 3.0, 6.0, 12.0 and 24.0 hours) under Urethane anesthesia (140 mg/100 g, i.p.). The brain, heart, lungs, liver, kidneys, spleen and thyroid were excised and blood collected. Young rats presented a shorter latency toxin concentration peak in all studied organs except for the liver and the kidney, when compared to adults. The ratio between the area under the curve of the toxin concentration in each organ and that in blood (Kp) indicates higher accumulation in the organs of young animals mainly for brain, liver and heart. These observations suggest a faster toxin distribution in the organs of young rats. The higher uptake of TsTX in the brain is suggestive of a greater permeability for the toxin along the blood-brain barrier of young rats. In conclusion, the higher uptake in heart, together with data from the brain, may help to elucidate the clinical manifestations frequently observed in children under scorpion envenomation.

Centrally injected tityustoxin produces the systemic manifestations observed in severe scorpion poisoning.

In this work we submitted adult male Wistar rats to intracerebroventricular (icv) and iv microinjections of the fraction tityostoxin (TsTX) from the Tityus serrulatus scorpion venom, to address whether the CNS could account for the systemic alterations previously reported: cardiac arrhythmias, lung edema, and seizures. Animals were injected icv, total volume of 1.0 microl, with either sterile saline (n = 4) or differing doses of TsTX (1.74, n = 5; 0.174, n = 4; 0.087, n = 5; and 0.058 microg, n = 4). The peripheral effect of the highest dose of TsTX used (1.74 microg) was tested through iv injections in the femoral vein (n = 4). All animals were recorded by a Video EEG/ECG system for a maximum period of 90 mins or until death. After recording, the lungs were harvested and weighed to evaluate edema (lung/body wt x100). Our results show that icv injections of TsTX, but not iv injections, were able to provoke heart arrhythmias, lung edema, and seizures. Furthermore, the toxin was capable of producing epileptiform discharges in all animals injected with 1.74 microg of the toxin. In conclusion, the action of TsTX in the CNS may solely account for the peripheral alterations observed in severe cases of Tityus serrulatus scorpion poisoning.

Cardiovascular and respiratory interactions of hyperosmolar saline, scorpion toxin, and veratridine in rats.

This study evaluates the cardiovascular and respiratory effects evoked by hypertonic sodium chloride solution (HSS) and the possible interactions of these effects with scorpion toxin (TX) or veratridine (V). Groups 1 (1 mL/kg, rapid), 2 (4 mL/kg, rapid), and 3 (4 mL/kg, slow) were used for comparison of HSS administered by rapid or slow injection. HSS (4 mL/kg) was injected after bilateral vagotomy (group 4) or administration of atropine (group 5). In groups 6 (1 mL/kg in bolus), 7 (4 mL/kg in bolus), and 8 (4 mL/kg/60 s), HSS was injected 20 min after the administration of TX (250 microg/kg). In group 9, two doses of V (25 microg/kg, i.v.) were injected 10 min apart. Concomitantly with the second dose of V, HSS (4 mL/kg) was injected into the jugular vein. HSS administered by rapid injection (1 mL/kg) resulted in hypotension, hyperventilation, and a slight decrease in heart rate. However, when HSS was administered after TX, only bradypnea was observed. HSS (4 mL/kg, rapid) induced a rapid and marked fall in blood pressure, bradycardia, and apnea. However, when HSS was administered after TX, a more pronounced bradycardia and a smaller reduction in mean arterial pressure were observed. Slow injection of HSS (60 s) evoked hypotension, hyperventilation, and bradycardia. The same dose injected after TX resulted in bradypnea and a smaller reduction in blood pressure. The HSS-induced hypotension was attenuated by previous administration of atropine or by vagotomy, whereas bradycardia was prevented by previous injection of atropine, but not by bilateral vagotomy. Like vagotomy, atropinization prevented the apnea and bradypnea produced by HSS (4 mL/kg in bolus). V evoked a slight bradycardia, hypotension, and apnea. These effects were potentiated when V was injected concomitantly with HSS. The effects of HSS are dependent on both volume and speed of injection, and are affected by previous injection of TX or concomitant injection of V.

Phenobarbital blocks the lung edema induced by centrally injected tityustoxin in adult Wistar rats.

The aim of this study was to evaluate the ability of phenobarbital to block the lung edema observed after intracerebroventricular (icv) injections of tityustoxin (TsTX), a toxic fraction of the Tityus serrulatus venom. We injected 1.74 microg icv (1.0 microl) of TsTX in Wistar rats pre-treated with 0.1 ml intramuscular injections of sterile saline or phenobarbital (60 or 170 mg/kg body weight). After the experiments the lungs were harvested and the pulmonary index (PI = lung/body weight x 100) calculated. The animals pre-treated with saline developed severe lung edema (PI = 1.8 +/- 0.2) after TsTX icv injection whereas those that received 170 mg/kg of phenobarbital presented no lung edema (PI = 0.71 +/- 0.02). Our results suggest that the lung edema induced by TsTX is of neurogenic nature and that 170 mg/kg of phenobarbital blocks TsTX induced lung edema.