Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8545742 | Environmental Toxicology and Pharmacology | 2018 | 6 Pages |
Abstract
Several evidences have related the biochemical and pharmacological properties of thymol, but the possible neurotoxic effects of this compound remain unknown and not evaluated. Thus, the purpose of this study was to evaluate whether intake of thymol in different doses (10, 20 and 40â¯mg/kg) induce neurotoxicity and behavioral alterations using mice as experimental model, as well as the involvement of blood-brain barrier (BBB) and brain neurotransmitters in these alterations. Thymol (20 and 40â¯mg/kg) significantly decrease latency time to inhibitory avoidance task when compared to control group, indicating a memory loss after 30 days of oral treatment. Also, thymol (20 and 40â¯mg/kg) induced a significant increase on BBB permeability to Evan's blue dye when compared to control group, which is an indicative of BBB breakdown. Moreover, a significant increase of brain acetylcholinesterase (AChE) was observed in mice treated with 40â¯mg/kg of thymol, while the activity of sodium-potassium pump (Na+, K+-ATPase) was inhibited in mice treated with 20 and 40â¯mg/kg thymol when compared to control group. Finally, mice that received 20 and 40â¯mg/kg thymol showed a significant increase on cerebral reactive oxygen species (ROS) levels and cerebral xanthine oxidase (XO) activity compared to control group. Based on these evidences, the rupture of BBB can be considered an important pathway linked in thymol-induced memory loss. Also, the augmentation of brain ROS levels elicited by increase on XO activity may be a via involved in the damage to BBB, and an oxidative pathway that impairs the activity of brain neurotransmitters, as AChE and Na+, K+-ATPase. In summary, the dose of 10â¯mg/kg thymol can be safe and without neurotoxic effects in a period of 30 days of intake.
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Authors
Matheus D. Baldissera, Carine F. Souza, Antônio Francisco Igor M. De Matos, Pedro Henrique Doleski, Bernardo Baldisserotto, Aleksandro S. Da Silva, Silvia G. Monteiro,