Abstract Aging is characterized by several neurochemical modifications involving structural proteins and neurotransmitters. Exercise has been recognized as an enhancer of overall health; whereas, diphenyl diselenide (PhSe)2 has been reported to have antioxidant, anti-inflammatory, and neuroprotective effects in rodents. A combination of pharmacological and non-pharmacological interventions has been proposed to prevent the aging effects. This study aimed to determine the swimming exercise and (PhSe)2 dietary supplementation synergic effects on the [3H] γ-aminobutyric acid (GABA) uptake in aged rats. Male Wistar rats (24 months) received 1 ppm of (PhSe)2 supplemented in the standard chow for 4 weeks. Rats were subjected to swimming training (20 min per day for 4 weeks). After 4 weeks, the [3H]GABA uptake was determined in samples of cerebral cortex and striatum of rats. The results of the present study demonstrate that the association of (PhSe)2-supplemented diet and swimming exercise was effective against the decrease of cerebral cortical and striatal [3H]GABA uptake in aged rats. The association of (PhSe)2 dietary supplementation with swimming exercise modulated the GABA uptake in cerebral structures of aged rats.

Este artigo de revisão aborda uma reflexão sobre o potencial terapêutico ou tóxico de compostos orgânicos de selênio, dando particular ênfase ao disseleneto de difenila e alguns dos seus análogos estruturais. Algumas características moleculares relacionadas com a toxicidade e farmacologia do disseleneto de difenila in vitro e in vivo são abordadas. Os artigos revisados, que abordam experimentos in vivo, indicam que a interação do disseleneto de difenila com tióis pode determinar seu potencial farmacológico ou toxicológico. Além disso, uma limitada ativação da rota de toxicidade, isto é, a oxidação controlada de moléculas de alto peso molecular, que contém grupos tióis, poderia contribuir para os efeitos farmacológicos do disseleneto de difenila. Conclui-se que a síntese de compostos orgânicos de selênio deve ser direcionada para o desenvolvimento de novos disselenetos de diorganoila que possam interagir com alvos moleculares específicos.

In this review, we summarized the potential role of synthetic organoseleno compounds as therapeutic or toxic agents, giving emphasis almost exclusively to diphenyl diselenide, the simplest of the diaryl diselenides, and some of its analogs. We presented the main molecular aspects related to the in vitro toxicity and pharmacology of diphenyl diselenide and also provided in vivo data indicating that the interaction of diphenyl diselenide with thiols can dictate either its toxicological or pharmacological property. The papers covered in this review indicate that a limited activation of the "toxic pathway", i.e., a controlled oxidation of specific high molecular weight thiol-containing molecules could contribute to the pharmacological effects of diphenyl diselenide. In conclusion, this review reinforces the necessity of developing new diorganoyl diselenides that could interact with specific molecular targets.

O objetivo deste estudo foi investigar se a exposição aguda ao ditelureto de difenila [(PhTe)2] causaria prejuízo no desenvolvimento comportamental de filhotes de ratos. Os filhotes receberam uma injeção subcutânea de (PhTe)2 (0,1 mg kg-1, 3 mL kg-1) ou veículo (3 mL kg-1) no 14º dia após o nascimento (DPN). Do 15º ao 21º DPN, foram realizados testes comportamentais nos filhotes e, imediatamente após estes testes, os filhotes foram submetidos à eutanásia. As análises histológicas, a determinação do conteúdo de mielina e a atividade da acetilcolinesterase (AChE) foram realizadas. O período crítico de intoxicação ocorreu no 4º e 5º dias após a injeção de (PhTe)2, quando os sinais de toxicidade foram mais evidentes, caracterizados pelo aparecimento de sinais sistêmicos de toxicidade, disfunções comportamentais, neurotoxicidade e uma alteração no sistema colinérgico. Desta forma, conclui-se que o (PhTe)2 induziu neurotoxicidade e prejuízos no desenvolvimento comportamental de filhotes de ratos.

The purpose of the present study was to investigate if acute exposure to diphenyl ditelluride (PhTe)2 causes impairment of developmental behavioral performance in rat pups. Rat pups received a single subcutaneous injection of (PhTe)2 (0.1 mg kg-1, 3 mL kg-1) or vehicle (3 mL kg-1) at 14th postnatal day. After exposure to (PhTe)2, the general parameters of neurotoxicity, behavioral tasks, cerebral myelin content, histological analysis and acetilcholinesterase (AChE) activity were performed during seven days. The appearance of classic signs of toxicity, behavioral alterations and the reduction in myelin content were dependent on the time after (PhTe)2 exposure to pups. Neuronal damage, reduction of myelin content, and the increase in AChE activity occurred mainly at 4th and 5th day after (PhTe)2 exposure, indicating that the critical period of neurotoxicity is coincident with the major behavioral alterations. In conclusion, exposure to (PhTe)2 induced neurotoxicity and impairment of developmental behavioral in rat pups.