XXXV Reunião Anual da SBBqResumoID:9371


Kinetic and toxicological effect of tacrine (Cognex ®) with the venom of Krait (Bungaraus caeruleus) acetylcholinesterase and human serum butrylcholinesterase activity

Mushtaq Ahmed*; João Batista T. Rocha; Maria R.C. Schetinger



Departamento de Quimica, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Laboratório de Bioquímica Toxicológica, 97105-900, Santa Maria, RS, Brazil

 

*Corresponding author: mushtaq213@yahoo.com


Elapidae poisoning is well known due its highly toxicity and death is common in several parts of the world, particularly in Asia. Death caused by Bungarus poisoning can at least in part be related to the presence of high quantities of acetylcholinesterase (AChE) in its venom. Kinetic parameters of the effect of tacrine as a cholinesterase inhibitor have been studied on two different sources. (1) snake venom (Bungaraus caeruleus) acetylcholinesterase (AChE),(2) human serum butyrylcholinesterase (BChE).Tacrine inhibited both venom acetylcholinesterase (AChE) as well as human serum butyrylcholinesterase (BChE) in a concentration dependent manner. Kinetic study indicates that the nature of inhibition was mixed for both enzymes i.e. Km values increase and Vmax decrease by increase of tacrine concentration. The calculated IC50 for snake venom as well as for human serum were being about 31 nM and 26 nM respectively. Ki was observed to be 13 nM for venom acetlcholinesterase (AChE) and 12 nM for serum butrylcholinesterase (BChE). KI (dissociation constant of AChE-ASCh-tacrine complex into AChE-ASCh complex and tacrine) was estimated 20 nM for venom and 10 nM for serum butrylcholinesterase (BChE), while the γKm (dissociation constt of AChE-ASCh-tacrine complex into AChE-tacrine complex and ASCh) were 0.086 mM and 0.147 mM for snake venom acetylcholinesterase (AChE) as well as for serum butrylcholinesterase (BChE) respectively. We demonstrated for the first time that this therapeutic agent used for the the treatment of Alzheimer's disease can also be considered an inhibitor of snake venom and human serum butyrylcholinesterase.

Supported by CNPq/TWAS