RESUMO
This study evaluated the most common toxic agents affecting domestic cats, the clinical signs of toxicity, and the therapeutic approaches for recovery. A survey on poisoning in cats was conducted among small animal veterinary practitioners from 2017 to 2018. Of the 748 completed questionnaires, 543 (72.6%) were evaluated. Pesticides and household cleaning supplies were the most common causes of poisoning in cats. The toxicant groups included pesticides and household cleaning supplies (organophosphates), human drugs (acetaminophen), plants/plant derivatives (lily), and veterinary drugs (tramadol). The major clinical signs for these four groups of toxicants were (1) acetaminophen poisoning, which caused oxidative erythrocyte damage; (2) muscarinic and nicotinic cholinergic syndrome, which resulted from organophosphate poisoning; (3) acute kidney injury, which resulted from intoxication of lily; and (4) serotonin syndrome, which resulted from tramadol toxicosis. Interventions for treating poisoning in cats were based on the clinical presentation of animals. In the present study, the significant toxins identified to be dangerous for cats were characterized using the obtained data in Brazil as well as the main associated clinical signs and therapy recommended by veterinarians.(AU)
Objetiva-se com este trabalho caracterizar os principais toxicantes para gatos domésticos, bem como os prevalentes sinais clínicos e a terapêutica associada. Uma pesquisa sobre envenenamento em gatos foi realizada entre médicos veterinários no período de 2017 a 2018. Dos 748 questionários preenchidos, 543 (72,6%) foram avaliados. Pesticidas e domissanitários foram os principais causadores de intoxicação em gatos. Entre os grupos tóxicos, destacaram-se, na categoria pesticidas e domissanitários (organofosforados), medicamentos humanos (acetaminofeno), plantas e derivados de planta (lírio) e medicamentos veterinários (tramadol). Os principais sinais clínicos para os quatro grupos de substâncias tóxicas foram: (1) intoxicação por acetaminofeno, que causou dano eritrocitário oxidativo; (2) síndrome colinérgica muscarínica e nicotínica, resultante do envenenamento por organofosforado; (3) lesão renal aguda, causada pela intoxicação por lírio; e (4) síndrome serotoninérgica, resultante da exposição ao tramadol. As intervenções realizadas para o tratamento dos envenenamentos foram justificáveis mediante a apresentação clínica dos animais. Por meio dos dados obtidos, puderam-se caracterizar os principais tóxicos para gatos no Brasil, bem como os principais sinais clínicos associados e a terapêutica preconizada pelos médicos veterinários.(AU)
Assuntos
Animais , Gatos , Compostos Organofosforados/toxicidade , Intoxicação/etiologia , Intoxicação/veterinária , Tramadol/toxicidade , Lilium/toxicidade , Acetaminofen/toxicidade , Serotoninérgicos/toxicidade , Estresse Oxidativo , Antagonistas Muscarínicos/toxicidade , Injúria Renal Aguda/induzido quimicamenteRESUMO
We examined whether lithium carbonate (Li2CO3, 100mg/L) is able to prevent memory impairment induced by scopolamine. Moreover, we evaluated the effects of lithium on anxiety-like behavior and acetylcholinesterase activity in adult zebrafish. We demonstrated that lithium prevents the memory impairment induced by scopolamine, decreases exploration and increases the activity of acetylcholinesterase in zebrafish. Collectively, this contributes to a better understanding of the pharmacology of lithium, its interaction with cholinergic neurotransmission, and its possible application to therapeutic treatments aimed at improving cognition.
Assuntos
Carbonato de Lítio/uso terapêutico , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/prevenção & controle , Escopolamina/toxicidade , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/uso terapêutico , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Feminino , Carbonato de Lítio/farmacologia , Masculino , Aprendizagem em Labirinto/fisiologia , Transtornos da Memória/psicologia , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Antagonistas Muscarínicos/toxicidade , Peixe-ZebraRESUMO
Systemic (IP) and/or intraseptal (IS) administration of scopolamine (SCP) and diazepam (DZP) induce amnesia, whereas IP injection of the neuropeptide substance P (SP) and choline chloride (ChCl) produce memory facilitation. The septohippocampal cholinergic system has been pointed out as a possible site of SCP and DZP-induced amnesia as well as for the mnemonic effects induced by SP and ChCl. We performed a series of experiments in order to investigate the interactions between cholinergic and GABA/benzodiazepine (GABA/BZD) systems with the SPergic system on inhibitory avoidance retention. Male Wistar rats were trained and tested in a step-down inhibitory avoidance task (1.0 mA footshock). Animals received, pre-training, IP (1.0 mg/kg) or IS (1.0 nM/0.5 microl) injection of DZP, SCP (SCP; 1.0 mg/kg - IP or 0.5 microM/0.5 microl--IS) or vehicle (VEH). Immediately after training they received an IP or IS injections of SP 1-11 (50 microg/kg--IP or 1.0 nM/0.5 microl--IS), SP 1-7 (167 microg/kg--IP or 1.0 nM/0.5 microl--IS), ChCl (20 mg/kg--IP or 0.3 microM/0.5 microl--IS) or VEH. Rats pretreated with SCP and DZP showed amnesia. Post-trial treatments with SP 1-11, SP 1-7 or ChCl blocked the amnesic effects of SCP and DZP. These findings suggest an interaction between SPergic and cholinergic mechanisms with GABAergic systems in the modulation of inhibitory avoidance retention and that the effects of these treatments are mediated, at least in part, by interactions in the septohippocampal pathway.
Assuntos
Amnésia/prevenção & controle , Colina/uso terapêutico , Diazepam/toxicidade , Substâncias Protetoras/uso terapêutico , Escopolamina/toxicidade , Substância P/uso terapêutico , Amnésia/induzido quimicamente , Animais , Aprendizagem da Esquiva , Moduladores GABAérgicos/toxicidade , Masculino , Antagonistas Muscarínicos/toxicidade , Neurônios/efeitos dos fármacos , Fragmentos de Peptídeos/uso terapêutico , Ratos , Ratos Wistar , Retenção Psicológica/efeitos dos fármacosRESUMO
This study was conducted to evaluate the effects of exposure to diphenyl diselenide (PhSe)2 on cognitive impairment induced by scopolamine, a muscarinic antagonist, using the Y-maze and Morris water maze tests in mice. One hour before the tests, mice were treated with (PhSe)2 (50 mg/kg, oral) and 30 min later memory impairment was induced by administration of scopolamine (1 mg/kg, intraperitoneal). (PhSe)2 (50 mg/kg, oral) significantly improved scopolamine-induced memory impairment in the Y-maze test. At the probe trial session in Morris water maze, (PhSe)2 (50 mg/kg, oral) significantly decreased the escape latency, increased the number of crossings in the platform local, and increased the time spent in the platform quadrant when compared with the scopolamine-treated group. General locomotor activity was similar in all groups. This study showed that (PhSe)2 ameliorated the impairments of spatial long-term memory and short-term memory, showed by the performance of mice in the Morris water maze and Y-maze tasks, respectively. These results suggest that (PhSe)2 may be useful for the treatment of cognitive impairment that may hold significant therapeutic value in alleviating certain memory deficits observed in Alzheimer's disease.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Derivados de Benzeno/farmacologia , Transtornos da Memória/tratamento farmacológico , Compostos Organosselênicos/farmacologia , Doença de Alzheimer/fisiopatologia , Animais , Modelos Animais de Doenças , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Atividade Motora/efeitos dos fármacos , Antagonistas Muscarínicos/toxicidade , Escopolamina/toxicidade , Fatores de TempoRESUMO
All five subtypes of muscarinic acetylcholine receptors (mAChR; M(1)-M(5)) are expressed in the hippocampus, where they are involved both in cognitive functions and in synaptic plasticity, such as long-term potentiation (LTP). Muscarinic toxins (MTs) are small proteins from mamba snake venoms that display exquisite discrimination between mAChRs. MT1 acts as an agonist at M(1) and an antagonist at M(4) receptors, with similar affinities for both. MT3, the most selective antagonist available for M(4) receptors, infused into the CA1 region immediately after training caused amnesia in the rat, indicating the participation of M(4) receptors in memory consolidation. Our goal was to investigate the participation of M(4) receptor in neurotransmission at the hippocampal Schaffer collaterals-CA1 synapses. Two different preparations were used: 1) field potential recordings in freshly prepared rat hippocampal slices with high-frequency stimulation to induce potentiation and 2) whole-cell voltage clamp in cultured hippocampal organotypic slices with paired stimuli. In preparation 1, a dose of MT3 that was previously shown to cause amnesia blocked LTP; the nonselective antagonist scopolamine blocked LTP without affecting basal transmission, although it was depressed with higher concentration. In preparation 2, basal transmission was decreased and LTP induction was prevented by an MT3 concentration that would bind mainly to M(4) receptors. Although M(1) receptors appeared to modulate transmission positively at these excitatory synapses, M(1) activation concomitant with M(4) blockade (by MT1) only allowed a brief, short-term potentiation. Accordingly, M(4) blockade by MT3 strongly supports a permissive role of M(4) receptors and suggests their necessary participation in synaptic plasticity at these synapses.
Assuntos
Hipocampo/fisiologia , Neurônios/fisiologia , Receptor Muscarínico M4/fisiologia , Sinapses/fisiologia , Transmissão Sináptica , Animais , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Técnicas In Vitro , Peptídeos e Proteínas de Sinalização Intercelular , Potenciação de Longa Duração/efeitos dos fármacos , Masculino , Antagonistas Muscarínicos/toxicidade , Neurônios/efeitos dos fármacos , Neurotoxinas/toxicidade , Técnicas de Patch-Clamp , Peptídeos/toxicidade , Ratos , Ratos Wistar , Receptor Muscarínico M4/antagonistas & inibidores , Escopolamina/toxicidade , Sinapses/efeitos dos fármacosRESUMO
This study verifies the effects of bovine brain phosphatidylserine (PS) on passive avoidance (PA) and contextual fear conditioning (CFC) tests in scopolamine-treated mice. Mice received daily i.p. 50 mg/kg PS or 0.2 M Tris pH 7.4 (TRIS) for 5 days. On day 6, mice received saline (TRIS-SAL and PS-SAL) or 1 mg/kg SCO (TRIS-SCO and PS-SCO) i.p. After 20 min, the animals were submitted to PA (experiment 1) or CFC (experiment 2) training sessions, and tests were performed 24 h later. Latency in entering the dark chamber of the PA apparatus presented by TRIS-SCO (but not PS-SCO) group in the test was significantly higher than those presented by controls. Except for TRIS-SCO, all the groups presented higher latencies in the test compared to the training session. In experiment 2, the TRIS-SCO (but not PS-SCO) group presented significantly lower freezing duration than that presented by the TRIS-SAL group in the test. Animals treated with PS alone presented higher freezing duration than that presented by the TRIS-SAL group. The results demonstrate that PS attenuates SCO-induced amnesia in both PA and CFC tests. In addition, PS per se improves retention in the CFC test.
Assuntos
Amnésia/prevenção & controle , Química Encefálica/fisiologia , Antagonistas Muscarínicos/toxicidade , Fosfatidilserinas/farmacologia , Escopolamina/antagonistas & inibidores , Escopolamina/toxicidade , Amnésia/induzido quimicamente , Animais , Aprendizagem por Associação/efeitos dos fármacos , Aprendizagem da Esquiva/efeitos dos fármacos , Bovinos , Condicionamento Psicológico/efeitos dos fármacos , Emoções/efeitos dos fármacos , Medo/fisiologia , Masculino , Memória/efeitos dos fármacos , CamundongosRESUMO
Five new piperidine alkaloids were designed from natural (-)-3-O-acetyl-spectaline and (-)-spectaline that were obtained from the flowers of Senna spectabilis (sin. Cassia spectabilis, Leguminosae). Two semi-synthetic analogues (7 and 9) inhibited rat brain acetylcholinesterase, showing IC50 of 7.32 and 15.1 microM, and were 21 and 9.5 times less potent against rat brain butyrylcholinesterase, respectively. Compound 9 (1mg/kg, i.p.) was fully efficacious in reverting scopolamine-induced amnesia in mice. The two active compounds (7 and 9) did not show overt toxic effects at the doses tested in vivo.
Assuntos
Acetilcolinesterase/química , Alcaloides , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/farmacologia , Desenho de Fármacos , Piperidinas , Plantas Medicinais/química , Alcaloides/síntese química , Alcaloides/química , Alcaloides/farmacologia , Amnésia/induzido quimicamente , Amnésia/tratamento farmacológico , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Butirilcolinesterase/química , Inibidores da Colinesterase/química , Flores/química , Masculino , Camundongos , Estrutura Molecular , Antagonistas Muscarínicos/toxicidade , Piperidinas/síntese química , Piperidinas/química , Piperidinas/farmacologia , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , Escopolamina/toxicidade , Relação Estrutura-AtividadeRESUMO
Wet dog shakes (WDS) and head shakes (HS) are associated with experimentally induced convulsive seizures. We sought to determine whether these behaviors are correlated or not with major (status epilepticus (SE) or fully kindled animals) or minor (non-SE or partially kindled animals) seizure severity. WDS are directly correlated with SE induced by intracerebral star fruit extract (Averrhoa carambola) injection and with kindled animals in the amygdala fast kindling model. On the other hand, WDS are inversely correlated with SE induced by intracerebral bicuculline and pilocarpine injections. Systemic pilocarpine in animals pretreated with methyl-scopolamine barely induced WDS or HS. The role of shaking behaviors may vary from ictal to anticonvulsant depending on the experimental seizure model, circuitries involved, and stimulus intensity. The physical presence of acrylic helmets may per se inhibit the HS response. Also, methyl-scopolamine, a drug incapable of crossing the blood-brain barrier, can induce HS in animals without acrylic helmets.