RESUMO
Lysosomal storage diseases are inherited or acquired disorders characterized by dysfunctional lysosomes that lead to intracytoplasmic accumulation of undegraded substrates, causing impaired cellular function and death. Many acquired lysosomal storage diseases are produced by toxic plants, which have indolizidine alkaloids, including swainsonine, that inhibits lysosomal α-mannosidase and Golgi α-mannosidase II. Swainsonine-induced nervous disease associated with various plants has been reported, including species of the genus Astragalus, Sida, Oxitropis, Swainsona, and Ipomoea. Two species of Astragalus (i.e. Astragalus garbancillo and Astragalus punae) have been found to cause neurologic disease in llamas. In addition, A. garbancillo was also associated with malformations in the offspring, and possibly abortions and neonatal mortality in llamas. The diagnosis of Astragalus spp. intoxication is established based on clinical signs, microscopic and ultrastructural findings, lectin histochemistry, abundance of these plants in the grazing area and determination of swainsonine in plant specimens.
Assuntos
Astrágalo , Swainsonina , Animais , Astrágalo/química , Doenças por Armazenamento dos Lisossomos/veterinária , Doenças por Armazenamento dos Lisossomos/induzido quimicamente , Intoxicação por Plantas/veterinária , Feminino , MasculinoRESUMO
Plants belonging to the genera Astragalus, Oxytropis, Ipomoea, Sida, and Swainsona often contain the toxin swainsonine (SW) produced by an associated fungal symbiont. Consumption of SW-containing plants causes a serious neurological disorder in livestock, which can be fatal. In this study, a fungal endophyte, Alternaria section Undifilum, was identified in Astragalus garbancillo seeds, using polymerase chain reaction (PCR) followed by direct sequencing. In seeds, the SW concentrations were about 4 times higher than in other parts of the plant. Furthermore, microscopic examination demonstrated that the fungus mycelium grows inside the petioles and stems, on the outer surface and inside the mesocarp of the fruit, in the mesotesta and endotesta layers of the seed coat, and inside the endosperm of the seeds. Our results support the notion that the SW-producing fungus is vertically transmitted in the host plant A. garbancillo.
Assuntos
Astrágalo , Fabaceae , Alternaria/genética , Simbiose , Astrágalo/microbiologia , Swainsonina/análiseRESUMO
Several plants that contain indolizidine alkaloids, including swainsonine, are toxic to livestock, causing dysfunctional lysosomes and storage disease. Swainsonine induces a neurovisceral disease, known as locoism, in sheep, goats, and cattle, which occurs in several parts of the world, including, but not limited to, the western United States, China, and parts of Australia. In South America, locoism has been described in the Andean region of Argentina affecting sheep, cattle, and llamas. Intoxication by consumption of Astragalus punae was suspected in 4 llamas in Jujuy Province, northwestern Argentina. The grazing area contained abundant specimens of A. punae. The clinical course was ~15 d, and included moderate ataxia, incoordination of hindlimbs, and progressive loss of body condition. Microscopically, fine cytoplasmic microvacuolation was observed in the proximal convoluted renal tubules. Ultrastructurally, these changes consisted of severely dilated lysosomes. Swainsonine was detected in stem and leaf samples of A. punae at a concentration of 0.06%. Based on clinical history and signs, histologic and ultrastructural changes, and plant analysis, a diagnosis of swainsonine toxicosis caused by consumption of A. punae was made, which has not been reported previously, to our knowledge.
Assuntos
Astrágalo , Camelídeos Americanos , Doenças dos Bovinos , Intoxicação por Plantas , Doenças dos Ovinos , Animais , Argentina/epidemiologia , Bovinos , Intoxicação por Plantas/epidemiologia , Intoxicação por Plantas/veterinária , Ovinos , Doenças dos Ovinos/epidemiologia , Swainsonina/análise , Swainsonina/toxicidadeRESUMO
Ipomoea carnea is a toxic plant found in Brazil and other tropical countries. The plant contains the alkaloids calystegines and swainsonine, which inhibit key cellular enzymes and cause systematic cell death. It is known that swainsonine is excreted in the amniotic fluid of dams exposed to the plant. Thus, the aim of this study was to verify whether the toxic effect of I. carnea on fetuses is due to exclusively the passage of the active principle of the plant through the placenta, or if the placentotoxic effect of swainsonine could collaborate in the adverse effects observed in the fetus. The teratogenic effects of exposure to the toxic principles of I. carnea were evaluated not only using the conventional protocol but also at later stages in the postnatal developmental period. Females were treated, from gestation day (GD) 6 until GD19, with 0.0, 1.0, 3.0 or 7.0 g/kg body weight of I. carnea dry leaves. The plant did not induce changes in reproductive performance or biochemical profile of the dams. Dams that received the highest dose of I. carnea showed cytoplasmic vacuolization in the liver, kidney and placental tissue. I. carnea promoted different lectin binding patterns in different areas of placental tissue. No fetal skeletal or visceral malformations was observed. The postnatal evaluation revealed a lower litter weight and a lower pup body weight one day after birth in the group that received the highest dose of I. carnea. Physical milestones were unaffected by the treatments. Female pups from all experimental groups exhibited a delay in achieving a negative geotaxis response. The results show that the toxic principle of I. carnea produces injury in utero in mothers and fetuses, but these deleterious effects were better demonstrated using postnatal evaluation.
Assuntos
Ipomoea , Extratos Vegetais/toxicidade , Plantas Tóxicas , Swainsonina/toxicidade , Alcaloides , Animais , Brasil , Feminino , Feto , Cabras , Rim , Fígado , Masculino , Folhas de Planta , Gravidez , Ratos , Reprodução , Testes de Toxicidade , TropanosRESUMO
Swainsonine has been identified as the toxin in legumes belonging to the genera Astragalus and Oxytropis throughout the world including China, North America, and South America. Several South American Astragalus species have been reported to contain swainsonine; however, data is lacking to support the presence of a fungal symbiont in South American Astragalus species as has been shown for North American and Chinese Astragalus and Oxytropis species. The objective of this study was to investigate several South American species that have been reported to contain swainsonine for the presence of the fungal symbiont using culturing and PCR. Swainsonine was detected in field collections of A. pehuenches, A. illinii and A. chamissonis but not A. moyanoi, which is consistent with reports of toxicity regarding these species. The symbiont Alternaria section Undifilum was detected by PCR in all three species that contained swainsonine but not in A. moyanoi. A fungal symbiont was isolated from seeds of Astragalus pehuenches and A. illinii. The isolated symbiont from both respective species produced swainsonine in vitro, and was demonstrated to belong to the genus Alternaria section Undifilum by analysis of the nuclear ribosomal DNA. It is highly likely that Alternaria section Undifilum isolates will be associated with other South American Astragalus species that are reported to contain swainsonine.
Assuntos
Alternaria/metabolismo , Astrágalo/microbiologia , Swainsonina/análise , Alternaria/classificação , Alternaria/genética , Argentina , Astrágalo/química , DNA Fúngico , DNA Ribossômico , Endófitos/metabolismo , Sementes/química , Sementes/microbiologiaRESUMO
The indolizidine alkaloid swainsonine, found in some Astragalus and Oxytropis (i.e., locoweed) species, is a potent cellular glycosidase inhibitor that often poisons livestock. Other toxic genera such as some Ipomoea species also contain swainsonine as well as calystegines which are similar polyhydroxy alkaloids. The toxicity of calystegines is poorly characterized; however, they are also potent glycoside inhibitors capable of intestinal and cellular glycoside dysfunction. The objective of this study was to directly compare A. lentiginosus and I. carnea poisoning in goats to better characterize the role of the calystegines. Three groups of four goats each were treated with ground alfalfa (control), I. carnea or A. lentiginosus to obtain daily doses of 0.0, 1.5, and 1.5â¯mg swainsonine/kg bw per day, respectively, for 45 days. Animals were observed daily and weekly body weights, serum enzyme activities, and serum swainsonine concentrations were determined. At day 45 all animals were euthanized and necropsied. Goats treated with A. lentiginosus and I. carnea developed clinical disease characterized by mild intention tremors and proprioceptive deficits. Goats treated with A. lentiginosus developed clinical disease sooner and with greater consistency. No differences in body weight, serum swainsonine concentrations and serum enzyme activity were observed between goats treated with A. lentiginosus and I. carnea. Additionally, there were no differences in the microscopic and histochemical studies of the visceral and neurologic lesions observed between goats treated with A. lentiginosus and I. carnea. These findings suggest that I. carnea-induced clinical signs and lesions are due to swainsonine and that calystegines contribute little or nothing to toxicity in goats in the presence of swainsonine.
Assuntos
Astrágalo/intoxicação , Doenças das Cabras/etiologia , Ipomoea/intoxicação , Intoxicação por Plantas/veterinária , Swainsonina/intoxicação , Animais , Doenças das Cabras/enzimologia , Doenças das Cabras/patologia , Cabras , Masculino , Propriocepção/efeitos dos fármacos , Swainsonina/sangue , Tremor/veterinária , Tropanos/intoxicaçãoRESUMO
Cervical cancer, caused by high oncogenic risk Human Papillomavirus (HPV) infection, continues to be a public health problem, mainly in developing countries. Using peptide phage display as a tool to identify potential molecular targets in HPV associated tumors, we identified α-mannosidase, among other enriched sequences. This enzyme is expressed in both tumor and inflammatory compartment of the tumor microenvironment. Several studies in experimental models have shown that its inhibition by swainsonine (SW) led to inhibition of tumor growth and metastasis directly and indirectly, through activation of macrophages and NK cells, promoting anti-tumor activity. Therefore, the aim of this work was to test if swainsonine treatment could modulate anti-tumor immune responses and therefore interfere in HPV associated tumor growth. Validation of our biopanning results showed that cervical tumors, both tumor cells and leukocytes, expressed α-mannosidase. Ex vivo experiments with tumor associated macrophages showed that SW could partially modulate macrophage phenotype, decreasing CCL2 secretion and impairing IL-10 and IL-6 upregulation, which prompted us to proceed to in vivo tests. However, in vivo, SW treatment increased tumor growth. Investigation of the mechanisms leading to this result showed that SW treatment significantly induced the accumulation of myeloid derived suppressor cells in the spleen of tumor bearing mice, which inhibited T cell activation. Our results suggested that SW contributes to cervical cancer progression by favoring proliferation and accumulation of myeloid cells in the spleen, thus exacerbating these tumors systemic effects on the immune system, therefore facilitating tumor growth.
Assuntos
Proliferação de Células/efeitos dos fármacos , Swainsonina/farmacologia , Neoplasias do Colo do Útero/patologia , alfa-Manosidase/metabolismo , Animais , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Quimiocina CCL2/metabolismo , Progressão da Doença , Feminino , Humanos , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Leucócitos/citologia , Leucócitos/metabolismo , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Células Supressoras Mieloides/citologia , Células Supressoras Mieloides/efeitos dos fármacos , Células Supressoras Mieloides/metabolismo , Swainsonina/uso terapêutico , Microambiente Tumoral/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/virologia , alfa-Manosidase/antagonistas & inibidoresRESUMO
This is the first report of a spontaneous outbreak of Astragalus pehuenches poisoning on a farm in Argentine Patagonia, where 63 out of 70 cattle died. The main clinical signs of affected animals were ataxia, balance loss and progressive emaciation. Purkinje cells presented vacuolation and marginalization of the nucleus. Astragalus pehuenches was detected in the paddock as well as in the ruminal content and fecal matter samples of the affected animals. Swainsonine concentrations in Astragalus specimens were found to be as high as 0.096%.
Assuntos
Astrágalo/intoxicação , Doenças dos Bovinos/epidemiologia , Fabaceae/química , Intoxicação por Plantas/veterinária , Animais , Argentina , Ataxia/veterinária , Bovinos , Doenças dos Bovinos/etiologia , Surtos de Doenças , Emaciação/veterinária , Swainsonina/análiseRESUMO
Numerous plant species worldwide including some Ipomoea (Convolvulaceae) and Sida (Malvaceae) species in Brazil cause lysosomal storage disease in herbivores and are known to contain swainsonine and calystegines as the main toxic compounds. The aim of this work was to determine swainsonine and calystegines concentrations in species of Convolvulaceae from the semiarid region of Pernambuco. Seven municipalities in the Moxotó region were visited and nine species were collected and screened for the presence of swainsonine and calystegines using an HPLC-APCI-MS method. The presence and concentration of these alkaloids within the same and in different species were very variable. Seven species are newly reported here containing swainsonine and/or calystegines. Ipomoea subincana contained just swainsonine. Ipomoea megapotamica, I. rosea and Jacquemontia corymbulosa contained swainsonine and calystegines. Ipomoea sericosepala, I. brasiliana, I. nil, I. bahiensis and I. incarnata contained just calystegines. The discovery of six Ipomoea species and one Jacquemontia species containing toxic polyhydroxy alkaloids reinforces the importance of this group of poisonous plants to ruminants and horses in the semiarid region of Pernambuco. Epidemiological surveys should be conducted to investigate the occurrence of lysosomal storage disease associated to these new species.(AU)
Numerosas espécies de plantas em todo o mundo, incluindo algumas espécies de Ipomoea (Convolvulaceae) e Sida (Malvaceae) no Brasil, causam doença de armazenamento lisossomal em herbívoros e são conhecidas por conterem swainsonina e calisteginas como princípios tóxicos. O objetivo deste trabalho foi determinar a concentração de swainsonina e calisteginas em espécies de Convolvulaceae da região semiárida de Pernambuco. Sete municípios na região do Sertão do Moxotó foram visitados, onde foram coletadas amostras das folhas de nove espécies de Convolvulaceae para avaliação da presença de swainsonina e calisteginas utilizando-se cromatografia líquida com espectrometria de massa. A presença e concentração destes alcaloides nas folhas de plantas da mesma espécie e dentre as espécies foram muito variáveis. Seis novas espécies de Ipomoea e uma espécie de Jacquemontia contendo swainsonina e/ou calisteginas são relatadas neste estudo. Ipomoea subincana continha apenas swainsonina. Ipomoea megapotamica, I. rosea e Jacquemontia corymbulosa continham swainsonina e calisteginas. Ipomoea sericosepala, I. brasiliana, I. nil, I. bahiensis e I. incarnata continham apenas calisteginas. A descoberta de novas espécies de Ipomoea e Jacquemontia contendo alcaloides polihidroxílicos tóxicos reforçam a importância deste grupo de plantas tóxicas para ruminantes e equinos na região semiárida de Pernambuco. Pesquisas epidemiológicas devem ser realizadas para investigar a ocorrência de doença de depósito lisossomal associada a essas novas espécies.(AU)
Assuntos
Animais , Plantas Tóxicas/intoxicação , Swainsonina/intoxicação , Convolvulaceae/intoxicação , Ipomoea/toxicidade , Ruminantes , Doenças por Armazenamento dos Lisossomos/veterinária , CavalosRESUMO
Numerous plant species worldwide including some Ipomoea (Convolvulaceae) and Sida (Malvaceae) species in Brazil cause lysosomal storage disease in herbivores and are known to contain swainsonine and calystegines as the main toxic compounds. The aim of this work was to determine swainsonine and calystegines concentrations in species of Convolvulaceae from the semiarid region of Pernambuco. Seven municipalities in the Moxotó region were visited and nine species were collected and screened for the presence of swainsonine and calystegines using an HPLC-APCI-MS method. The presence and concentration of these alkaloids within the same and in different species were very variable. Seven species are newly reported here containing swainsonine and/or calystegines. Ipomoea subincana contained just swainsonine. Ipomoea megapotamica, I. rosea and Jacquemontia corymbulosa contained swainsonine and calystegines. Ipomoea sericosepala, I. brasiliana, I. nil, I. bahiensis and I. incarnata contained just calystegines. The discovery of six Ipomoea species and one Jacquemontia species containing toxic polyhydroxy alkaloids reinforces the importance of this group of poisonous plants to ruminants and horses in the semiarid region of Pernambuco. Epidemiological surveys should be conducted to investigate the occurrence of lysosomal storage disease associated to these new species.(AU)
Numerosas espécies de plantas em todo o mundo, incluindo algumas espécies de Ipomoea (Convolvulaceae) e Sida (Malvaceae) no Brasil, causam doença de armazenamento lisossomal em herbívoros e são conhecidas por conterem swainsonina e calisteginas como princípios tóxicos. O objetivo deste trabalho foi determinar a concentração de swainsonina e calisteginas em espécies de Convolvulaceae da região semiárida de Pernambuco. Sete municípios na região do Sertão do Moxotó foram visitados, onde foram coletadas amostras das folhas de nove espécies de Convolvulaceae para avaliação da presença de swainsonina e calisteginas utilizando-se cromatografia líquida com espectrometria de massa. A presença e concentração destes alcaloides nas folhas de plantas da mesma espécie e dentre as espécies foram muito variáveis. Seis novas espécies de Ipomoea e uma espécie de Jacquemontia contendo swainsonina e/ou calisteginas são relatadas neste estudo. Ipomoea subincana continha apenas swainsonina. Ipomoea megapotamica, I. rosea e Jacquemontia corymbulosa continham swainsonina e calisteginas. Ipomoea sericosepala, I. brasiliana, I. nil, I. bahiensis e I. incarnata continham apenas calisteginas. A descoberta de novas espécies de Ipomoea e Jacquemontia contendo alcaloides polihidroxílicos tóxicos reforçam a importância deste grupo de plantas tóxicas para ruminantes e equinos na região semiárida de Pernambuco. Pesquisas epidemiológicas devem ser realizadas para investigar a ocorrência de doença de depósito lisossomal associada a essas novas espécies.(AU)