No abstract

Different types of epilepsy and forms of pathological anxiety have been described as significant neurological disorders that may exist as comorbidities. Some of those disorders share the association of affected limbic areas/neuropathological triggers as well as the use of drugs for their clinical management. The aim of this work was to investigate the anticonvulsant and anxiolytic properties of the vitexin (apigenin-8-Cglucoside), since this compound is a flavonoid usually found as one of the major constituents in several medicinal plants claimed as anxiolytics and/or anticonvulsants. This investigation was performed by the use of a series of classical murine animal models of chemically induced-seizures and of anxiety-related tests (open-field, elevated plusmaze, and light-dark box tests). Here, we show that the systemic administration of vitexin (1.25; 2.5 and 5 mg/kg; i.p.) exhibited selective protection against chemically-induced seizures. Vitexin did not block seizures evoked by glutamate receptors agonists (NMDA and kainic acid), and it did not interfere with the latencies for these seizures. Conversely, the same treatments protected the animals in a dose-dependent manner against the seizures evoked by the Gabaergic antagonists picrotoxin and PTZ and rise the latency time for the first seizure on non-protected animals. The higher dose of vitexin protected 100% of animals against the tonic-clonic seizures triggered by GABA antagonists. The results from open-field, elevated plus-maze, and light-dark box tests indicated the anxiolytic properties of vitexin at similar range of doses described for the anticonvulsant action screening. Furthermore, these results pointed that vitexin did not cause sedation or locomotor impairment on animals. The selective action of vitexin against picrotoxin and PTZ may reinforce the hypothesis by which this compound acts mainly by the modulation of GABAergic neurotransmission and/or related pathways. This could be useful to explain the dual activity of vitexin as anticonvulsant and anxiolytic, and highlight the pharmacological interest on this promising flavonoid.

No tratamento da água potável são utilizados produtos clorados de modo a garantir o nível de segurança sanitária exigido. Contudo, na presença de precursores, pode ocorrer a formação de Subprodutos da Desinfecção (SPD) em decorrência da reação com o cloro. O SPD Cloral Hidratado (CH), composto hipnótico e sedativo, tem sido encontrado na água, no entanto não é citado no padrão de potabilidade brasileiro. Este trabalho tem como objetivo geral avaliar o risco toxicológico do CH a partir de ensaios específicos e calcular um Valor Máximo Permissível (VMP). Roedores foram expostos a diferentes concentrações padronizadas de CH e submetidos a análises bioquímicas e bioensaios comportamentais e de locomoção, tais quais os de campo aberto, indução de sono e rotarod. Foi identificado o Nível de Efeito Adverso Não Observado (NOAEL) na dose 9,60 mg.kg-1.d-1, obtendo-se o VMP de 2,3 mg.L-1 de CH; considerando o Nível de Menor Efeito Observado (LOAEL) na dose 0,96 mg.kg-1.d-1, obteve- se o VMP de 0,023 mg.L-1 de CH, valor próximo ao 0,02 mg.L-1 citado nos padrões da Austrália (2017) e da Nova Zelândia (2017). Palavras-chave: Água potável. Avaliação de risco. Cloral hidratado. LOAEL. NOAEL. Subprodutos da desinfecção.

Depression and anxiety are common neuropsychiatric disorders that usually appear as comorbidities. The development of new drugs is crucial for safer and more effective clinical management of both disorders. Riparin A is a synthetic chemical analog of riparins that naturally occur in several medicinal plants. Marked pharmacological effects such as anxiolytic and antidepressant properties characterize this class of compounds. However, little is known about the potential anxiolytic and antidepressant effects of Riparin A. In this work, we showed that, unlike other riparins, Riparin A exerts only a very mild anxiolyticlike effect as demonstrated by the results of classical behavioral tests such as the elevated plus-maze, lightdark box and open-field tests in rats. However, all doses of Riparin A (2.5; 5.0 and 10 mg/kg; intraperitoneal) have shown significant antidepressant activity in rats submitted to forced swimming test. In addition to this interesting pharmacological property, Riparin A did not promote any important alterations in the locomotor performance of the animals as specifically demonstrated by the rotarod test. Furthermore, Riparin A did not induce sedation in treated animals; instead, this compound appears to increase the animal's state of alertness as measured by the latency time to loss of reflexes and time to recovery from sleep in rats submitted to the pentobarbital-induced sleep time test. The present results point to an antidepressant effect of Riparin A and reinforce the pharmaceutical interest in the group of riparins, particularly their high potential for use in new studies investigating the structure-activity relationships between member compounds. Behavioural