Clinical and pathological aspects and cerebellar lectin binding in cattle poisoned with Solanum fastigiatum var. fastigiatum and Solanum bonariense

Microscopic and lectin histochemical studies were performed using the cerebella of 33 natural cases of Solanum fastigiatum var. fastigiatum intoxication in the cattle from southern Brazil and 2 natural and 4 experimental cases of Solanum bonariense from Uruguay. The following biotinylated lectins were used in both cases: WGA, sWGA, BS-I, Con-A, RCA-I, DBA, and UEA-I, with the addition of LCA in S. fastigiatum poisoning cases. Histologically, the lesions consisted of fine vacuolization, distention of portions of the Purkinje cells, axonal spheroids measuring 14-50 m in the granular cell layer and adjacent white matter and, proliferation of the Bergmann?s glia. Lectin histochemistry revealed strong reactivity of stored material in Purkinje neurons with the lectins sWGA, Con-A, and LCA in S. fastigiatum cases. A similar pattern was found in S. bonariense cases with a most intense reactions to WGA, and less intense reaction to Con-A, whereas BS-I and RCA-I binding was absent to poor in these neurons in all the cases studied.Lectin reactivity in Purkinje cells between cases was independent of cell damage (from mild to severe loss of neurons). Both S. fastigiatum and S. bonariense have similar lectin binding,  suggesting a similar pathogenesis. Since comparable binding patterns have been described in animals poisoned with swainsonine-containing plants, perhaps the toxins in these plants contain related glycosidaseinhibiting toxins or inhibit glycoprotein and lysosomal metabolism through some related mechanism. The results of this study showed that in spontaneous poisoning by S. fastigiatum and S. bonariense in the cattle, the pattern of lectin binding is similar to those observed in S. fastigiatum experimental conditions.Fil: Sant’Ana, Fabiano J.F.. Universidade Federal de Santa Catarina; BrasilFil: Barbeito, Claudio Gustavo. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Nishida, Fabian. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Gimeno, Eduardo Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Verdes, José M.. Universidad de la República. Facultad de Ciencias; UruguayFil: Moraña, Antonio. Universidad de la República; UruguayFil: Barros, Claudio S.L.. Universidad de la República; Urugua

Cerebellar Cortical Degeneration in Cattle Poisoned with <i>Solanum</i> spp. in South America: An Epidemiological, Clinicopathological, Pathological, and Toxicological Review

Cattle that consume Solanum bonariense L (= Solanum fastigiatum Willd.) or Solanum paniculatum L. develop a typical cerebellar cortical degeneration characterized by periodic episodes of ataxia, hypermetria, hyperesthesia, head and thoracic limb extension, opisthotonus, nystagmus, and falling to the side or backward. Histological lesions include vacuolation, degeneration, and loss of Purkinje cells. Axonal spheroids, microcavitations, and other changes of Wallerian degeneration in cerebellar granular layer and white matter are also observed. Neurotoxic compounds in Solanum spp. causing neurologic dysfunction in ruminants were not definitively elucidated. The same Solanaceae species are extensively used with culinary purposes or for the treatment of liver and gastrointestinal disorders as hangovers in humans. In the present paper, we review the epidemiology, clinical signs, and pathological hallmarks of poisoning by Solanum —S. bonariense L. (=S. fastigiatum Willd.) and S. paniculatum—with emphasis in histopathology, ultrastructural, and lectin- and immuno-histochemical changes in spontaneous and experimentally poisoned cattle in South America. The current knowledge of the pathogenesis of these bovine cerebellar cortical degenerations is discussed, and some advances in botanical and toxicological aspects of these Solanaceae species are presented, taking into account the potential risk of human poisoning.Facultad de Ciencias Veterinaria

Cerebellar Cortical Degeneration in Cattle Poisoned With Solanum spp. in South America: An Epidemiological, Clinicopathological, Pathological, and Toxicological Review

Cattle that consume Solanum bonariense L (= Solanum fastigiatum Willd.) or Solanum paniculatum L. develop a typical cerebellar cortical degeneration characterized by periodic episodes of ataxia, hypermetria, hyperesthesia, head and thoracic limb extension, opisthotonus, nystagmus, and falling to the side or backward. Histological lesions include vacuolation, degeneration, and loss of Purkinje cells. Axonal spheroids, microcavitations, and other changes of Wallerian degeneration in cerebellar granular layer and white matter are also observed. Neurotoxic compounds in Solanum spp. causing neurologic dysfunction in ruminants were not definitively elucidated. The same Solanaceae species are extensively used with culinary purposes or for the treatment of liver and gastrointestinal disorders as hangovers in humans. In the present paper, we review the epidemiology, clinical signs, and pathological hallmarks of poisoning by Solanum —S. bonariense L. (=S. fastigiatum Willd.) and S. paniculatum—with emphasis in histopathology, ultrastructural, and lectin- and immuno-histochemical changes in spontaneous and experimentally poisoned cattle in South America. The current knowledge of the pathogenesis of these bovine cerebellar cortical degenerations is discussed, and some advances in botanical and toxicological aspects of these Solanaceae species are presented, taking into account the potential risk of human poisoning.Fil: Verdes, Jose M.. Universidad de la República; UruguayFil: Riet Correa, Franklin. Federal University of Campina Grande; BrasilFil: Medeiros, Rosane M.T.. Federal University of Campina Grande; BrasilFil: Moraña, Antonio. Universidad de la República; UruguayFil: Battes, Daniel. Universidad de la República; UruguayFil: Dehl, Virginia. Universidad de la República; UruguayFil: Borteiro, Claudio. Universidad de la República; UruguayFil: Gimeno, Eduardo Juan. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sant’Ana, Fabiano J.F.. Universidade Federal de Goiás; BrasilFil: Barros, Claudio S.L.. Federal University of Santa Maria; BrasilFil: Barros, Servero S.. Federal University of Santa Maria; Brasi

Calbindin D28k Expression and the Absence of Apoptosis in the Cerebellum of Solatium bonariense L-lntoxicated Bovines

Solanum bonariense intoxication is characterized by cerebellar neuronal vacuolation, degeneration, and necrosis. Cerebellar Purkinje cells seem especially susceptible, but more research is needed to determine the pathogenesis of neuronal necrosis and the mechanism of Purkinje cell susceptibility. Calbindin D28k (CbD28k) is highly expressed in Purkinje cells and has been used as a marker for normal and degenerative Purkinje cells. The goal of this study was to describe S bonariense-induced disease by ascertaining Purkinje cell-specific degenerative changes using CbD28k expression and to correlate this with apoptosis in Purkinje cells, as determined using TUNEL (transferase-mediated dUTP-biotin nick end-labeling) and ultrastructural changes. In all cases, an increase in both dose and duration of S bonariense intoxication resulted in a decrease in the number of Purkinje cells. CbD28k immunohistochemistry was an excellent marker for Purkinje cells because immunoreactivity did not change in normal or degenerative tissues. This finding suggests that excessive calcium excitatory stimulation does not induce rapid neuronal degeneration and death. As found in previous studies, TUNEL tests and electron microscopy suggest that Purkinje cell degeneration and death are not occurring via an apoptotic process. These findings suggest that S bonariense poisoning induces progressive Purkinje cell death that is not mediated by excitotoxicity or apoptotic activation.Facultad de Ciencias Veterinaria

Cerebellar Cortical Degeneration in Cattle Poisoned with <i>Solanum</i> spp. in South America: An Epidemiological, Clinicopathological, Pathological, and Toxicological Review

Cattle that consume Solanum bonariense L (= Solanum fastigiatum Willd.) or Solanum paniculatum L. develop a typical cerebellar cortical degeneration characterized by periodic episodes of ataxia, hypermetria, hyperesthesia, head and thoracic limb extension, opisthotonus, nystagmus, and falling to the side or backward. Histological lesions include vacuolation, degeneration, and loss of Purkinje cells. Axonal spheroids, microcavitations, and other changes of Wallerian degeneration in cerebellar granular layer and white matter are also observed. Neurotoxic compounds in Solanum spp. causing neurologic dysfunction in ruminants were not definitively elucidated. The same Solanaceae species are extensively used with culinary purposes or for the treatment of liver and gastrointestinal disorders as hangovers in humans. In the present paper, we review the epidemiology, clinical signs, and pathological hallmarks of poisoning by Solanum —S. bonariense L. (=S. fastigiatum Willd.) and S. paniculatum—with emphasis in histopathology, ultrastructural, and lectin- and immuno-histochemical changes in spontaneous and experimentally poisoned cattle in South America. The current knowledge of the pathogenesis of these bovine cerebellar cortical degenerations is discussed, and some advances in botanical and toxicological aspects of these Solanaceae species are presented, taking into account the potential risk of human poisoning.Facultad de Ciencias Veterinaria

Calbindin D28k Expression and the Absence of Apoptosis in the Cerebellum of Solatium bonariense L-lntoxicated Bovines

Solanum bonariense intoxication is characterized by cerebellar neuronal vacuolation, degeneration, and necrosis. Cerebellar Purkinje cells seem especially susceptible, but more research is needed to determine the pathogenesis of neuronal necrosis and the mechanism of Purkinje cell susceptibility. Calbindin D28k (CbD28k) is highly expressed in Purkinje cells and has been used as a marker for normal and degenerative Purkinje cells. The goal of this study was to describe S bonariense-induced disease by ascertaining Purkinje cell-specific degenerative changes using CbD28k expression and to correlate this with apoptosis in Purkinje cells, as determined using TUNEL (transferase-mediated dUTP-biotin nick end-labeling) and ultrastructural changes. In all cases, an increase in both dose and duration of S bonariense intoxication resulted in a decrease in the number of Purkinje cells. CbD28k immunohistochemistry was an excellent marker for Purkinje cells because immunoreactivity did not change in normal or degenerative tissues. This finding suggests that excessive calcium excitatory stimulation does not induce rapid neuronal degeneration and death. As found in previous studies, TUNEL tests and electron microscopy suggest that Purkinje cell degeneration and death are not occurring via an apoptotic process. These findings suggest that S bonariense poisoning induces progressive Purkinje cell death that is not mediated by excitotoxicity or apoptotic activation.Facultad de Ciencias Veterinaria

The Treatment With the SGLT2 Inhibitor Empagliflozin Modifies the Hepatic Metabolome of Male Zucker Diabetic Fatty Rats Towards a Protective Profile

[Abstract] The EMPA-REG OUTCOME (Empagliflozin, Cardiovascular Outcome Event Trial in patients with Type 2 Diabetes Mellitus (T2DM)) trial evidenced the potential of sodium-glucose cotransporter 2 (SGLT2) inhibitors for the treatment of patients with diabetes and cardiovascular disease. Recent evidences have shown the benefits of the SGLT2 inhibitor empagliflozin on improving liver steatosis and fibrosis in patients with T2DM. Metabolomic studies have been shown to be very useful to improve the understanding of liver pathophysiology during the development and progression of metabolic hepatic diseases, and because the effects of empagliflozin and of other SGLT2 inhibitors on the complete metabolic profile of the liver has never been analysed before, we decided to study the impact on the liver of male Zucker diabetic fatty (ZDF) rats of a treatment for 6 weeks with empagliflozin using an untargeted metabolomics approach, with the purpose to help to clarify the benefits of the use of empagliflozin at hepatic level. We found that empagliflozin is able to change the hepatic lipidome towards a protective profile, through an increase of monounsaturated and polyunsaturated glycerides, phosphatidylcholines, phosphatidylethanolamines, lysophosphatidylinositols and lysophosphatidylcholines. Empagliflozin also induces a decrease in the levels of the markers of inflammation IL-6, chemerin and chemerin receptor in the liver. Our results provide new evidences regarding the molecular pathways through which empagliflozin could exert hepatoprotector beneficial effects in T2DM.This work was supported by Boehringer Ingelheim Pharma GmbH and Co., by the National Institute of Health “Fondo de Investigaciones Sanitarias del Instituto de Salud Carlos III” Madrid, Spain (PI15/00681, PI17/00409, PI18/00821, PI20/00902, RETICS Programme RD16/0012/0014 and CIBER de Enfermedades Cardiovasculares (CIBERCV)); European Regional Development Fund (FEDER) and European Union framework MSCA-RISE-H2020 Programme (Project number 734899). AH-A was funded by predoctoral research grants from Xunta de Galicia and FPU Program of the Spanish Ministry of Science, Innovation and Universities (Spain); MF-S was funded by the predoctoral research grants “Programa Científico do Centro de Investigación en Medicina Molecular e Enfermidades Crónicas (CiMUS) (Spain) and Xunta de Galicia; and AV-L was funded by the predoctoral research grant from the PFIS Program of the Spanish Ministry of Science and Instituto de Salud Carlos III (Spain

Immunohistochemical analysis of cytoskeleton and ubiquitin in cerebellum of poisoned cattle by Solanum bonariense

El Solanum bonariense L., es un arbusto perenne, autóctono en Uruguay, Argentina y sur de Brasil. Al ser ingerido por los bovinos en pastoreo, les ocasiona una degeneración cortical cerebelosa, afectando específicamente a las células de Purkinje. Estas presentan el pericario extensamente vacuolado con desplazamiento del núcleo, con progresiva muerte neuronal. En los axones de estas neuronas se observa presencia de esferoides axonales en la sustancia blanca cerebelosa, que finalmente son sustituidos por microcavitaciones en la sustancia blanca. El objetivo del presente trabajo fue describir el patrón de inmunoreactividad contra diferentes elementos del citoesqueleto y la ubiquitina conjugada a proteínas marcadas para degradarse dentro de las células de Purkinje de cerebelos de bovinos intoxicados natural o experimentalmente por ingestión de Solanum bonariense L.Facultad de Ciencias Veterinaria

Calbindin d 28k expression in the cerebellum of normal and solanum bonariense L. Intoxicated bovines

La ingestión natural o experimental de Solanum bonariense L. ocasiona una degeneración cortical cerebelosa en bovinos. Esta lesión se debe a la degeneración específica de las células de Purkinje, postulándose que la misma se debe a alteraciones metabólicas específicas, demostradas previamente por estudios ultraestructurales e inmunohistoquímicos. La Calbindina-28kD (Cb28k) ha sido considerada como un marcador específico de células de Purkinje. La alteración de esta inmunoreacción se vincula al desarrollo de diferentes enfermedades neurodegenerativas en humanos. El objetivo del presente trabajo fue analizar la expresión de Cb28k en cerebelos de bovinos normales y en los intoxicados con Solanum bonariense L.Facultad de Ciencias Veterinaria