Tese
Os efeitos do ácido cafeico e do éster fenetil do ácido cafeico sobre as atividades da acetilcolinesterase e das ecto-nucleotidases em ratos
Fecha
2013-01-21Registro en:
ANWAR, Javed. THE EFFECTS OF CAFFEIC ACID AND CAFFEIC ACID
PHENETHYL ESTER ON THE ACTIVITIES OF
ACETYLCHOLINESTERASE AND ECTO-NUCLEOTIDASES IN RATS. 2013. 162 f. Tese (Doutorado em Ciências Biológicas) - Universidade Federal de Santa Maria, Santa Maria, 2013.
Autor
Anwar, Javed
Institución
Resumen
Phenolic compouds and their derivatives constitute a leading family of natural compounds. Caffeic acid (CA) and
caffeic acid phenethyl ester (CAPE) are the important members of phenolic compound, sharing several biological
applications; antioxidant, neuroprotective, anti-inflammatory, antiproliferative, antibacterial, antiviral, antiatherosclerotic and
anticancer properties. In spite of these, literature reportes some of its pro-oxidants activity depending on cellular
environment. These pathophysiolocal properties increased the interest to evaluate the effect of CA and CAPE on the enzyme
evolved in the purines salvage and the acetylcholine hydrolyzing enzyme the acetylcholineterase (AChE); in both PNS and
CNS, since the essential constituent of our dietary items. Previously, our research group has reported that phenolic compound
altered the activities of these enzymes. The AChE rapidly hydrolyzes the acetylcholine in neuronal and non neuronal tissues,
mediating several neurodegenerative diseases. Beside the ACh, ATP (as co-neurotramittors) and adenosine are important
signaling molecules, communicating cells in both PNS and CNS. In the extracellular signalling pathways; the adenine
nucleotides, their derivative and the coupling of these molecules with specific receptor have a crucial role in nervous,
vascular and immune systems. Once released, these molecules are hydrolyzed by a cascade of enzymes including
ectonucleoside triphosphate diphosphohydrolase (NTPDase; E.C. 3.6.1.5, CD39), 5 -nucleotidase (E.C 3.1.3.5, CD73),
ectonucleotide pyrophosphatase/phosphodiesterase (E-NPP), modulating crucially the signaling pathways in the normal
functioning of nervous, vascular and immune systems. Next, adenosine deaminase (ADA) and xanthin oxidase (XO) degrade
the adenosine and xanthine respectively which further control the functioning mechanisms in cellular events. Found in the
neuronal and non neuronal (in both PNS and CNS) the AChE, NTPDase, 5'-nucleotidase, E-NPP, and ADA regulate several
events including neurotransmission, inflammation, and thrombogenic process. We hypothesized to evaluate first the in vitro
effects of CA on AChE activity in peripheral and central cholinergic system of rats. The results showed that CA significantly
modulated the cholinergic system in vitro. By modulating the cholinergic system in vitro, apparently CA (e.g. phenolic
structure) has proper role in neurotransmission. Therefore we hypothesizes to evaluate the in vivo effects of CA on AChE,
NTPDase, E-NPP, 5'-nucleotidase, platelets aggregation and (ADA) in different tissues/cell from rats. The animals were
treated during 30 days and killed after behavioral test. The results showed that caffeic acid increased significantly the AChE
activity in hippocampus, hyphothalmus, pon and lymphocytes while that in cortex, cerebellum and striatum the AChE was
inhibited. CA improves step-down latencies in the inhibitory avoidance. Investigating the in vivo effects of CA in purinergic
system, caffecid acid increased the ATP and AMP hydrolysis in synaptosomes. However, in the synaptosomes no alterations
were observed in the ADA activity in the groups evaluated in this study. CA increased the ATP and AMP hydrolysis, while
the ADP hydrolysis was decreased in platelets. In the present findings caffeic acid decreased the platelets aggregation
induced by ADP agonist. Treatment with CA also increased the NTPDase and ADA activities in lymphocytes of rats.
Considering the dual function of caffeic acid in vitro and in vivo, the present study was extended to CAPE followed by acute
treatment model (ip) in order to elucidate the effect of another phenolic structure on the same parameters. In this line the
animals were treated (ip) with CAPE and killed after 40 minutes. In platelets, the results showed that the effect of CAPE
increased the NTPDase, E-NPP, 5 -nucleotidase activities, while ADA activities did not change significantly. In
synaptosomes CAPE significantly inhibited the NTPDase, and 5 -nucleotidase activity. CAPE induced no significant changes
in ADA in synaptosomes but reduced XO in whole brain. Finaly we investigated the activity of AChE in cortex, cerebellum,
striatum, hippocampus, hyphotalamus, pon, lymphocytes and muscules of rats treated with CAPE. The results showed that
CAPE significantly decreased the AChE activity in cortex cerebellum and striatum. CAPE significantly increased the AChE
activity in hippocampus hypothalamus, pons, muscle and lymphocytes. In cholinergic system our results clearly
demonstrating that both compound with dual functions.These findings demonstrated that the AChE activities and the cascade
of ecto-enzymes was alter in different tissues after treatment with CA and CAPE in rats, suggesting that these compound
should be considered a potentially therapeutic agent in immune, vascular and neurological disorders related with the
cholinergic purinergic system.