Browsing by Subject "Neurotoxicity"

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    A critical review about neurotoxic effects in marine mammals of mercury and other trace elements
    (Elsevier, 2020-05) López Berenguer, Gabriel; Peñalver, J.; Martínez-López, Emma; Ciencias Sociosanitarias
    Marine mammals are more exposed to mercury (Hg) than any others animals in the world. As many trace elements, Hg it is able to impair the brain function, which could be a cause of population decline. Nevertheless, these issues have been scarcely studied because of the technical and ethical difficulties. We conducted a systematic review about marine mammals’ brain exposition to Hg and other trace elements, and their neurotoxic effects. Information was scarce and the lack of standardization of nomenclature of brain structures, sample collecting and results presentation made it difficult to obtain conclusions. Hg was the most studied metal and toothed whales the most studied group. Despite being its target organ, brain accumulates lesser concentrations of Hg than other tissues as liver. We found a significant positive correlation between both organs’ burden (rho = 0.956 for cetaceans; rho = 0.756 for pinnipeds). Reported Hg values in brain of cetaceans (median 3.00 ppm ww) surpassed by one or two orders of magnitude those values found in other species as pinnipeds (median 0.33 ppm ww) or polar bears (median 0.07 ppm ww). Such values exceeded neurotoxicity thresholds. Although marine mammals ingest mostly the organic and more toxic form MeHg, different fractions of inorganic mercury can appear in brain, which could suggest some detoxification mechanisms. Other suggested mechanisms include Se–Hg interaction and liver sequestration. Although other elements are subjected to a rigid homeostatic control, appear in low concentrations or do not exert an important neurotoxic effect, they should be more studied to elucidate their neurotoxicity potential.
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    Comparison of chromaffin cells from several animal sources for their use as an in vitro model to study the mechanism of organophosphorous toxicity
    (Elsevier, 2006-04-28) Romero, D.; Quesada, E.; Sogorb, M. A.; Vilanova, E.; Carrera, V.; García Fernández, Antonio Juan; Ciencias Sociosanitarias
    It had been observed that the chromaffin cells of bovine adrenal medulla contain high levels of neuropathy target esterase (NTE), the esterase whose inhibition and aging is associated with induction of the organophosphorous induced delayed neuropathy. In this study, total esterase and NTE activities, and their inhibition kinetics by OPs are characterized in adrenal medulla of several species in order to find the best source for chromaffin cells. Total esterase activity in membrane fraction of bovine, equine, porcine, ovine and caprine were 6100±840, 4200±270, 5000±120, 28800±3000, and 10800±2400 mU/g tissue, respectively (mean±S.D., n = 3–4). NTE represented around 70%, 24%, 58%, 10% and 24% of the total esterases in the same tissues, respectively. It was deduced that NTE represents between 69% and 89% of the “B-activity” (activity resistant to 40 M paraoxon) in the membrane fraction of all species. The mipafox I50 calculated for 30-min inhibition of NTE at 37 ◦C ranged between 7.4 and 12 M. These values are in the range of that for brain NTE in hen (the usual model for testing OP delayed neurotoxicity). Considering that bovine adrenal medulla contains high NTE activity, that it represents a high proportion of total activity, it is easier to dissect than adrenal medulla from equine, caprine or ovine, and is more readily available than species cited previously, and that its inhibitory properties are similar to the classical hen brain model, it is deduced that bovine adrenal medulla is the most appropriate source of chromaffin cells to study OP toxicity, with porcine as the second alternative. The kinetic properties of chromaffin cell cultures from bovine and porcine were in accordance with their properties in homogenate and subcellular fractions, and they displayed an appropriate stability and viability of the primary culture to be used in in vitro toxicological studies for both mechanistic and testing purposes.
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    Lectinhistochemistry and ultrastructure of microglial response to monosodium glutamate-mediated neurotoxicity in the arcuate nucleus
    (Murcia : F. Hernández, 1999) Pelaez, B.; Blazquez, J.L.; Pastor, F.E.; Sánchez, A.; Amat, P.
    In this study we describe the most relevant morphological features of the microglial reaction that takes place in the arcuate nucleus (AN) after neurotoxic injury induced by a single subcutaneous injection of monosodium glutamate (MSG) in neonatal rats. The time course of the reaction was evaluated by lectinhistochemistry. Microglial/macrophagic cells were labelled with the lectin obtained from Lycopersicon esculentum and with B4 isolectin from Griffonia simplicifolia. The microglial response was also studied by ultrastructural observations. 'The histochemical study revealed the presence of few reactive microglial cells at 6 h post-injection. These cells were intensely stained and had a globular morphology but contained no neuronal debris inside them when observed under the electron microscope. At 12 h post-injection, the number of microglial cells had increased and, at the same time, intense phagocytic activity was observed ultrastructurally. The microglial reaction peaked at 24 and 36 h post-injection, when the number of microglial/ macrophagic cells was maximum, although the ultrastructural observations showed that at 36 h the amount of debris ingested by macrophages was decreased with respect to animals sacrificed at 24 h. Finally, at 4 days after neurotoxic injection the number and morphology of microglial cells were similar to those observed in the control rats. The ultrastructural study also revealed the existence of microglial cell mitosis in the territory of the AN together with a strong increase in the number of supraependymal cells resembling macrophages in the third ventricle during the lesion. Our data demonstrate that activated microglial cells initially extend throughout the damaged territory, but from 24-36 h onwards they are especially patent in the ventrolateral portions of the AN.
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    Urolithin A attenuates bupivacaine-induced neurotoxicity in SH-SY5Y cells by regulating the SIRT1-activated PI3K/AKT pathway
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Liu, Bin; Wei, Yuan
    Urolithin A (UroA) is well-recognized for its anti-oxidative, anti-inflammatory, and immuno-modulatory potentials and has been proven to have neuroprotective effects. Nevertheless, the potential of UroA on bupivacaine (BUP)-induced neurotoxicity has never been reported. Using SH-SY5Y cells to establish a cell model, it was revealed that BUP stimulated cell viability reduction, LDH release increase, and suppression of SIRT1-activated PI3K/AKT signaling in SH-SY5Y cells, whereas UroA treatment caused an effective abrogation of the effects of BUP. Besides, SIRT1 overexpression caused an enhancement in the activity of PI3K/AKT signaling in BUP and UroA co-treated cells, indicating that SIRT1 mediated the activity of PI3K/AKT signaling. Moreover, UroA inhibited BUP-induced apoptosis, oxidative stress, and inflammatory responses in SH-SY5Y cells. However, the effects of UroA on BUP-induced neurotoxicity were all abated by inhibiting SIRT1 or PI3K/AKT signaling through EX527 or LY294002. In conclusion, UroA protected SH-SY5Y cells against BUP-induced injuries through PI3K/AKT signaling in a SIRT1-dependent manner.