Tb II-I, a fraction isolated from Tityus bahiensis scorpion venom, alters cytokines': level and induces seizures when intrahippocampally injected in rats

Scorpion venoms are composed of several substances with different pharmacological activities. Neurotoxins exert their effects by targeting ion channels resulting in toxic effects to mammals, insects and crustaceans. Tb II-I, a fraction isolated from Tityus bahiensis scorpion venom, was investigated for its ability to induce neurological and immune-inflammatory effects. Two putative -sodium channel toxins were identified in this fraction, Tb2 II and Tb 4, the latter having been completely sequenced by mass spectrometry. Male Wistar rats, stereotaxically implanted with intrahippocampal cannulas and electrodes, were injected with Tb II-I (2 mu g/2 mu L) via the intrahippocampal route. The behavior, electrographic activity and cellular integrity of the animals were analyzed and the intracerebral level of cytokines determined. Tb II-I injection induced seizures and damage in the hippocampus. These alterations were correlated with the changes in the level of the cytokines tumoral necrosis factor- (TNF-) and interleukin-6 (IL-6). Therefore, the binding of Tb II-I to its target in the central nervous system may induce inflammation resulting in neuropathological and behavioral alterations.

Tb II-I, a fraction isolated from Tityus bahiensis scorpion venom, alters cytokines': level and induces seizures when intrahippocampally injected in rats

Scorpion venoms are composed of several substances with different pharmacological activities. Neurotoxins exert their effects by targeting ion channels resulting in toxic effects to mammals, insects and crustaceans. Tb II-I, a fraction isolated from Tityus bahiensis scorpion venom, was investigated for its ability to induce neurological and immune-inflammatory effects. Two putative -sodium channel toxins were identified in this fraction, Tb2 II and Tb 4, the latter having been completely sequenced by mass spectrometry. Male Wistar rats, stereotaxically implanted with intrahippocampal cannulas and electrodes, were injected with Tb II-I (2 mu g/2 mu L) via the intrahippocampal route. The behavior, electrographic activity and cellular integrity of the animals were analyzed and the intracerebral level of cytokines determined. Tb II-I injection induced seizures and damage in the hippocampus. These alterations were correlated with the changes in the level of the cytokines tumoral necrosis factor- (TNF-) and interleukin-6 (IL-6). Therefore, the binding of Tb II-I to its target in the central nervous system may induce inflammation resulting in neuropathological and behavioral alterations.

Perinatal effects of scorpion venoms: maternal and offspring development.

Scorpion envenomation is a public health problem, especially in tropical and subtropical countries. Considering the high incidence of scorpionism in some areas, pregnant women and nursing mothers may be possible victims. Scorpion stings alter the release of neurotransmitters and some cytokines. These mediators act as organizers and programmers in the adequate formation of the nerves, and non-physiological concentrations of them during the brain organization originate disorders and diseases that can appear later in the life of the individual. Despite the importance of this subject, there are only a few studies showing the effects of scorpion venom on maternal reproductive development, in the morphology and physical and behavioral development of offspring. The present review article summarizes the major findings on this issue. Biochemical changes in the blood - such as hyperglycemia, increase on the level of sodium and on the creatinine concentration - are observed after scorpion sting in humans and experimental animals. Some studies in the literature demonstrate that the scorpion venom affects the maternal reproductive development in humans and in experimental animals, increasing the frequency and amplitude of uterine contraction and the number of resorptions. The venom can also lead to some alterations in the embryonic or fetal development increasing the total weight of fetuses and of some organs. Moreover, it affects the general activity and locomotion during childhood and adulthood, and the anxiety level in adult females and males. It also alters the number of hippocampal neurons and interferes in the level of some cytokines. Altogether, it is evident that the venom, when administered during the pregnancy or lactation, affects the development of the offspring. Studies are being conducted to determine the actual participation of the venom in the development of the offspring, and to what extent they are detrimental to animal development.

Perinatal effects of scorpion venoms: maternal and offspring development

Scorpion envenomation is a public health problem, especially in tropical and subtropical countries. Considering the high incidence of scorpionism in some areas, pregnant women and nursing mothers may be possible victims. Scorpion stings alter the release of neurotransmitters and some cytokines. These mediators act as organizers and programmers in the adequate formation of the nerves, and non-physiological concentrations of them during the brain organization originate disorders and diseases that can appear later in the life of the individual. Despite the importance of this subject, there are only a few studies showing the effects of scorpion venom on maternal reproductive development, in the morphology and physical and behavioral development of offspring. The present review article summarizes the major findings on this issue. Biochemical changes in the blood - such as hyperglycemia, increase on the level of sodium and on the creatinine concentration - are observed after scorpion sting in humans and experimental animals. Some studies in the literature demonstrate that the scorpion venom affects the maternal reproductive development in humans and in experimental animals, increasing the frequency and amplitude of uterine contraction and the number of resorptions. The venom can also lead to some alterations in the embryonic or fetal development increasing the total weight of fetuses and of some organs. Moreover, it affects the general activity and locomotion during childhood and adulthood, and the anxiety level in adult females and males. It also alters the number of hippocampal neurons and interferes in the level of some cytokines. Altogether, it is evident that the venom, when administered during the pregnancy or lactation, affects the development of the offspring. Studies are being conducted to determine the actual participation of the venom in the development of the offspring, and to what extent they are detrimental to animal development.(AU)

Perinatal effects of scorpion venoms: maternal and offspring development

Abstract Scorpion envenomation is a public health problem, especially in tropical and subtropical countries. Considering the high incidence of scorpionism in some areas, pregnant women and nursing mothers may be possible victims. Scorpion stings alter the release of neurotransmitters and some cytokines. These mediators act as organizers and programmers in the adequate formation of the nerves, and non-physiological concentrations of them during the brain organization originate disorders and diseases that can appear later in the life of the individual. Despite the importance of this subject, there are only a few studies showing the effects of scorpion venom on maternal reproductive development, in the morphology and physical and behavioral development of offspring. The present review article summarizes the major findings on this issue. Biochemical changes in the blood - such as hyperglycemia, increase on the level of sodium and on the creatinine concentration - are observed after scorpion sting in humans and experimental animals. Some studies in the literature demonstrate that the scorpion venom affects the maternal reproductive development in humans and in experimental animals, increasing the frequency and amplitude of uterine contraction and the number of resorptions. The venom can also lead to some alterations in the embryonic or fetal development increasing the total weight of fetuses and of some organs. Moreover, it affects the general activity and locomotion during childhood and adulthood, and the anxiety level in adult females and males. It also alters the number of hippocampal neurons and interferes in the level of some cytokines. Altogether, it is evident that the venom, when administered during the pregnancy or lactation, affects the development of the offspring. Studies are being conducted to determine the actual participation of the venom in the development of the offspring, and to what extent they are detrimental to animal development.

Perinatal effects of scorpion venoms: maternal and offspring development

Scorpion envenomation is a public health problem, especially in tropical and subtropical countries. Considering the high incidence of scorpionism in some areas, pregnant women and nursing mothers may be possible victims. Scorpion stings alter the release of neurotransmitters and some cytokines. These mediators act as organizers and programmers in the adequate formation of the nerves, and non-physiological concentrations of them during the brain organization originate disorders and diseases that can appear later in the life of the individual. Despite the importance of this subject, there are only a few studies showing the effects of scorpion venom on maternal reproductive development, in the morphology and physical and behavioral development of offspring. The present review article summarizes the major findings on this issue. Biochemical changes in the blood - such as hyperglycemia, increase on the level of sodium and on the creatinine concentration - are observed after scorpion sting in humans and experimental animals. Some studies in the literature demonstrate that the scorpion venom affects the maternal reproductive development in humans and in experimental animals, increasing the frequency and amplitude of uterine contraction and the number of resorptions. The venom can also lead to some alterations in the embryonic or fetal development increasing the total weight of fetuses and of some organs. Moreover, it affects the general activity and locomotion during childhood and adulthood, and the anxiety level in adult females and males. It also alters the number of hippocampal neurons and interferes in the level of some cytokines. Altogether, it is evident that the venom, when administered during the pregnancy or lactation, affects the development of the offspring. Studies are being conducted to determine the actual participation of the venom in the development of the offspring, and to what extent they are detrimental to animal development.

Effect of maternal exposure to Tityus bahiensis scorpion venom during lactation on the offspring of rats.

Scorpion stings are a public health problem in Brazil and lactating women may be affected. We aimed to study the effects of Tityus bahiensis venom in the offspring of rats treated during lactation. Mothers received a subcutaneous injection of saline (1.0ml/kg) or venom (2.5mg/kg) or an intraperitoneal injection of LPS (lipopolysaccharide) (100µg/kg) on postnatal (PN) days 2 (PN2), 10 (PN10) or 16 (PN16). The offspring were evaluated during the childhood and adulthood. Pups showed a delay in physical and reflexological development, and a decrease in motor activity. Adults displayed low anxiety. There was an increase in the number of viable neuronal cells in hippocampal areas CA1 and CA4. The levels of IFN-γ (interferon-gamma) increased in the experimental groups. Several of the parameters analyzed showed important differences between the sexes. Thus, the scorpion venom affects the development in the offspring of mothers envenomed during the lactation.

Intrahippocampal injection of TsTX-I increases the levels of INF-γ in the cerebral tissue but not the levels of glutamate.

TsTX-I, isolated from Tityus serrulatus scorpion venom, causes epileptic-like discharges when injected into the central nervous system. The involvement of excitatory amino acids and cytokines in this activity was investigated. Our results have demonstrated that TsTX-I increases the release of IFN-γ but does not alter the intracerebral concentration of the excitatory amino acids in rats. Thus, this cytokine seems to be more important in the convulsive process than glutamate.

Participação de fatores de crescimento e de citosinas nas alterações observadas na prole de ratas tratadas com o veneno do escorpião Tityus Bahiensis no período gestacional / Participation of growth factors and citokynes in alterations observed in offspring of rats treated with Tityus bahiensis scorpion venom during the pregnancy

No Brasil, o escorpionismo é um problema de saúde pública. O escorpião T. serrulatus é considerado o mais perigoso, mas um grande número de acidentes também acontece com o T. bahiensis. O objetivo do estudo foi verificar possíveis efeitos do veneno do escorpião T. bahiensis no desempenho reprodutivo materno e nos níveis de citocinas e fatores de crescimento em embriões de mães tratadas durante a gestação. Para os parâmetros reprodutivos foram utilizadas fêmeas prenhes injetadas com uma dose de 2,5mg/Kg (s.c.) do veneno no 5º (GD5) ou no 10º (GD10) dia gestacional. O grupo controle foi injetado com salina a 1,46% (1ml/Kg) em ambos os dias. No 21º dia gestacional, os filhotes foram retirados por laparotomia e divididos em dois grupos que receberam tratamento específico para a análise visceral e esquelética. Para avaliação dos níveis de citocinas e de fatores de crescimento, as fêmeas prenhes foram injetadas com salina (1ml/Kg), LPS (100μg/kg) ou veneno (2,5mg/Kg) no 10º (GD10) ou 16º (GD16) dia gestacional. Os filhotes foram removidos por laparotomia 6, 12 ou 24 horas após o tratamento materno. As amostras foram maceradas em um homogenizador de tecido e centrifugadas. Os níveis de citocinas e fatores de crescimento foram determinados por ensaios imunoenzimáticos. Nos parâmetros reprodutivos não houve alterações no peso materno durante a gestação, no número de corpos lúteos, número de filhotes, peso do útero e dos filhotes. Houve diminuição no número de implantações e reabsorções no grupo GD5. Houve aumento no peso das placentas em GD5 e GD10. No desenvolvimento dos filhotes foram observadas aumento no peso do coração e pulmão em GD5 e GD10 e no peso do fígado em GD10. Não foram observadas anomalias e malformações internas ou externas nos filhotes de ambos os grupos experimentais. Em GD10 não foram observadas alterações nos níveis de citocinas 6 horas após a aplicação do veneno, mas verificou-se diminuição do nível de INF-γ 24 horas depois...

In Brazil scorpionism is a public health problem. The scorpion T. serrulatus is considered the most dangerous, but a large number of accidents also occur with T. bahiensis. The objective of this work was to verify the possible effects of the T. bahiensis scorpion venom on the maternal reproductive parameters and on the cytokines levels and growth factors in embryos after the treatment of pregnancy females. To the reproductive parameters it was used pregnant females injected with a dose of 2.5mg/Kg (s.c.) of the venom. The experimental groups were injected with venom on the 5th (GD5) or on the 10th (GD10) gestational day. The control group was injected with NaCl 1.46% on both days. On the 21st gestational day, the pups were taken out by laparotomy and were divided into two groups that received specific treatments for skeletal or visceral analyses. To evaluate the cytokines levels, pregnant females were injected with saline (1ml/kg), LPS (100μg/kg) or crude venom (2.5mg/kg) on the 10th (GD10) or 16th (GD16) gestational day. The pups were removed by laparotomy 6, 12 or 24 hours after the mother’s treatment. The samples (embryo/placenta) were macerated by a tissue homogenizer and centrifuged. The cytokine levels were determined by enzyme immunoassays. In the reproductive parameters no changes were observed in the maternal weight during the gestational period, corpora lutea, number of pups, uterus weight and pups weight. There was a decrease on the number of implantation and resorption in GD5 There was alteration on the placenta’s weight in GD5 and GD10. In pups development there were observed alterations in the heart and lung weight on GD5 and GD10 and on the liver weight on GD10. There were not observed external or internal anomalies and malformations in the offspring of both experimental groups. The cytokines levels were not alterated after 6 hours in GD10. In GD16 there was an increase in the IL-1α levels...

Effects of in utero exposure to Tityus bahiensis scorpion venom in adult rats.

The toxicity of Tityus bahiensis scorpion venom is well known, but there are little data about the damage in offspring of dams that were exposed to the venom during pregnancy. The objective of this work was to determine the toxic effects of venom in adult offspring of Wistar rats exposed to venom in utero. Dams were divided into a control group, subcutaneously injected with saline solution on the 10th (GD10) and 16th (GD16) days, and two experimental groups, subcutaneously injected with venom (2.5mg/kg) on GD10 or GD16, respectively. Adult offspring were evaluated according to behavioral development and neuronal integrity in the hippocampus. Tests performed in the activity box and in the enriched environment demonstrated that males from GD10 had motor decrease. Females from GD10 showed a depressive-like state and were more anxious, as demonstrated by the forced swimming test and social interaction. The plus-maze discriminative avoidance task demonstrated that GD16 males had lower levels of anxiety. The number of neuronal cells was decreased in CA1, CA3 and CA4 hippocampal areas of males and females from GD10 group and in CA1 of females and CA4 of males from GD16 group. Thus, we conclude that venom exposure in pregnant dams causes subtle alteration in the behavioral and neuronal development of offspring in adult life in a gender-dependent manner.

Effects of in utero exposure to Tityus bahiensis scorpion venom in adult rats

The toxicity of Tityus bahiensis scorpion venom is well known, but there are little data about the damage in offspring of dams that were exposed to the venom during pregnancy. The objective of this work was to determine the toxic effects of venom in adult offspring of Wistar rats exposed to venom in utero. Dams were divided into a control group, subcutaneously injected with saline solution on the 10th (GD10) and 16th (GD16) days, and two experimental groups, subcutaneously injected with venom (2.5 mg/kg) on GD10 or GD16, respectively. Adult offspring were evaluated according to behavioral development and neuronal integrity in the hippocampus. Tests performed in the activity box and in the enriched environment demonstrated that males from GD10 had motor decrease. Females from GD10 showed a depressive-like state and were more anxious, as demonstrated by the forced swimming test and social interaction. The plus-maze discriminative avoidance task demonstrated that GD16 males had lower levels of anxiety. The number of neuronal cells was decreased in CA1, CA3 and CA4 hippocampal areas of males and females from GD10 group and in CA1 of females and CA4 of males from GD16 group. Thus, we conclude that venom exposure in pregnant dams causes subtle alteration in the behavioral and neuronal development of offspring in adult life in a gender-dependent manner.

Effects of prenatal exposure to Tityus bahiensis scorpion venom on rat offspring development.

Scorpion envenoming is a public health problem. In Brazil, the scorpion Tityus serrulatus is considered the most dangerous, but a large number of exposures also occur with Tityus bahiensis. There are quite a few studies in literature about the toxic effects of this venom but it is not known if the venom causes malformations or behavioral defects to the offspring of mothers exposed to the venom during pregnancy. The objective of this work was to determine, in rats, the possible toxic effects of T. bahiensis venom on offspring when injected into rats during different periods of fetal development. Rats were assigned to one of three groups: one control group and two experimental groups that were subcutaneously injected with venom (2.5mg/kg) on the 10th (GD10) or on 16th day (GD16) of gestation. Pups were evaluated for changes in physical and behavioral development. GD10 treatment group offspring showed an increase in body weight gain, earlier ear unfolding, incisor tooth eruption and vaginal opening. A decrease in the time of palmar grasp and surface-righting reflexes was observed only for males. In GD16 treatment group, earlier ear unfolding, incisor tooth eruption, and delay in eye opening were observed in the offspring. In female pups a decrease in weight gain and in time for palmar grasp reflex, and an increase in time for negative geotaxis were observed. In male pups a delay in the testis descent, decrease in the time of palmar grasp, increase in the time of negative geotaxis reflex and in the general and locomotor activities could be noticed. Therefore, we concluded that a moderate dose of scorpion venom administered to pregnant rats was able to elicit alterations in physical and behavioral development in the offspring during the postnatal period.

Effects of prenatal exposure to Tityus bahiensis scorpion venom on rat offspring development

Scorpion envenoming is a public health problem. In Brazil, the scorpion Tityus serrulatus is considered the most dangerous, but a large number of exposures also occur with Tityus bahiensis. There are quite a few studies in literature about the toxic effects of this venom but it is not known if the venom causes malformations or behavioral defects to the offspring of mothers exposed to the venom during pregnancy. The objective of this work was to determine, in rats, the possible toxic effects of T. bahiensis venom on offspring when injected into rats during different periods of fetal development. Rats were assigned to one of three groups: one control group and two experimental groups that were subcutaneously injected with venom (2.5 mg/kg) on the 10th (GD10) or on 16th day (GD16) of gestation. Pups were evaluated for changes in physical and behavioral development. GD10 treatment group offspring showed an increase in body weight gain, earlier ear unfolding, incisor tooth eruption and vaginal opening. A decrease in the time of palmar grasp and surface-righting reflexes was observed only for males. In GD16 treatment group, earlier ear unfolding, incisor tooth eruption, and delay in eye opening were observed in the offspring. In female pups a decrease in weight gain and in time for palmar grasp reflex, and an increase in time for negative geotaxis were observed. In male pups a delay in the testis descent, decrease in the time of palmar grasp, increase in the time of negative geotaxis reflex and in the general and locomotor activities could be noticed. Therefore, we concluded that a moderate dose of scorpion venom administered to pregnant rats was able to elicit alterations in physical and behavioral development in the offspring during the postnatal period.

Exposição pré-natal ao veneno do escorpião Tityus bahiensis: efeitos na prole de ratos / Prenatal exposure to the Tityus bahiensis venom: effects on the offspring of rats

No Brasil, os escorpiões Tityus serrulatus e o Tityus bahiensis são os mais perigosos e desenvolveram hábitos domiciliares podendo ser encontrados dentro das construções humanas. A peçonha do escorpião é conhecida por sua alta toxicidade, mas não existem estudos sobre seu efeito na prole de mães que o recebem. O objetivo do trabalho foi verificar possíveis efeitos tóxicos da peçonha do T. bahiensis na prole quando administrada às ratas prenhes. A dose utilizada do veneno foi 2,5 mg/Kg. As fêmeas prenhes foram separadas em 3 grupos: controle (C) e experimentais injetadas com veneno no 10°dia (E10) ou no 16°dia (E16) gestacional. Na fase pós-natal, os animais foram avaliados quanto ao seu desenvolvimento físico e reflexológico. Na idade adulta foram avaliados quanto ao seu desenvolvimento comportamental. Nos filhotes de E10 houve adiantamento do desdobramento das orelhas, da erupção dos dentes e da abertura vaginal; diminuição do tempo de ocorrência do reflexo de preensão palmar no 8º dia de vida e do reflexo postural no 4º dia de vida dos machos. Na idade adulta os animais de E10 apresentaram diminuição da atividade total e da locomoção dos machos na caixa de atividade e no ambiente enriquecido; diminuição da latência para parar de nadar em fêmeas; aumento no número de entradas no braço não-aversivo e dos braços abertos do labirinto em cruz, na sessão de treinamento; diminuição do tempo de permanência no braço não-aversivo e aumento do tempo de permanência nos braços abertos do labirinto em cruz elevado, na sessão de teste. Na contagem celular feita nas áreas hipocampais de filhotes adultos de E10 foi observada perda neuronal significante nas áreas de CA1 e CA3. Nos filhotes de E16 houve adiantamento do desdobramento das orelhas e erupção dos dentes; atraso da abertura dos olhos e descida dos testículos; diminuição do tempo de ocorrência do reflexo de preensão palmar no 6º e no 8º dia de vida das fêmeas e no 8º dia de vida dos machos; ocorrência em maior tempo.

Exposição pré-natal ao veneno do escorpião Tityus bahiensis: efeitos na prole de ratos

No Brasil, os escorpiões Tityus serrulatus e o Tityus bahiensis são os mais perigosos e desenvolveram hábitos domiciliares podendo ser encontrados dentro das construções humanas. A peçonha do escorpião é conhecida por sua alta toxicidade, mas não existem estudos sobre seu efeito na prole de mães que o recebem. O objetivo do trabalho foi verificar possíveis efeitos tóxicos da peçonha do T. bahiensis na prole quando administrada às ratas prenhes. A dose utilizada do veneno foi 2,5 mg/Kg. As fêmeas prenhes foram separadas em 3 grupos: controle (C) e experimentais injetadas com veneno no 10°dia (E10) ou no 16°dia (E16) gestacional. Na fase pós-natal, os animais foram avaliados quanto ao seu desenvolvimento físico e reflexológico. Na idade adulta foram avaliados quanto ao seu desenvolvimento comportamental. Nos filhotes de E10 houve adiantamento do desdobramento das orelhas, da erupção dos dentes e da abertura vaginal; diminuição do tempo de ocorrência do reflexo de preensão palmar no 8º dia de vida e do reflexo postural no 4º dia de vida dos machos. Na idade adulta os animais de E10 apresentaram diminuição da atividade total e da locomoção dos machos na caixa de atividade e no ambiente enriquecido; diminuição da latência para parar de nadar em fêmeas; aumento no número de entradas no braço não-aversivo e dos braços abertos do labirinto em cruz, na sessão de treinamento; diminuição do tempo de permanência no braço não-aversivo e aumento do tempo de permanência nos braços abertos do labirinto em cruz elevado, na sessão de teste. Na contagem celular feita nas áreas hipocampais de filhotes adultos de E10 foi observada perda neuronal significante nas áreas de CA1 e CA3. Nos filhotes de E16 houve adiantamento do desdobramento das orelhas e erupção dos dentes; atraso da abertura dos olhos e descida dos testículos; diminuição do tempo de ocorrência do reflexo de preensão palmar no 6º e no 8º dia de vida...