Dual Effect of Alternariol on Acetyl Cholinesterase and Monoamineoxidase Extracted from Different Parts of Rat Brain

Abstract

Alternariol is a metabolite product of different strains of alternaria tenuis fungus. It’s structure has a similarity to cannabinol derivatives and it has a chemical formula 3,4,5 trihydroxy 6- methyl dibenzoxy-α–pyrone. The effect of the alternariol on both acetylcholinesterase (AChE) and monoamineoxidase (MAO-A) enzymes extracted from whole and five different parts of male albino rat brains; namely: frontal cortex, basal ganglia, cerebellum, pons, medulla oblongata was studied. Kinetic studies were done to determine the type of inhibition of AChE and MAO-A enzymes and the enzyme –inhibitor dissociation constants (Ki) by alternariol.The results indicated that alternariol inhibited both AChE and MAO –A enzymes of the cortex and medulla oblongata more than the extracts of the other parts of the brain. These parts are responsible for perception, motor, sensory, psychic activities and reflex centers of respiration.The inhibition of these enzymes increased with increasing the amount of alternariol added to the assay mixture, i.e., the inhibition was dose dependent and of the competitive type. The values of Ki for alternariol – AChE enzyme extracts varied from 12.0 to 15.0 mmol/L and for alternariol – MAO enzyme extracts varied from 28 to 30 mmol/L and were of the same order of magnitude.The difference in the degree of inhibition of the extracts of these brain parts could be attributed to the slight difference in the structure i.e; arrangement of their amino acids (isozyme phenomenon) and to their distinct gene loci.The inhibition of AChE and MAO-A by alternariol may save ACh and biogenic amines which are of great importance for the patients suffering from Alzheimers and dementia.

Keywords

• acetylcholine
• 5 hydroxytryptamine (serotonin)
• alternariol
• acetyl cholinesterase
• monoamine oxidase