Diazinon altera a atividade das colinesterases periféricas sem alterar o comportamento de camundongos

Abstract

Organophosphorus compounds (OP) belong to a class of chemical compounds which contain a pentavalent phosphorus atom in its structure, which is bound by a double bond to an oxygen atom or to a sulfur atom. They are commonly used as war gas and also as pesticides in agriculture and veterinary medicine. Diazinon (DZ) is an OP of the phosphorothioate class, and like all OP, is characterized by the ability to inhibit cholinesterases (ChEs), causing damage mainly to the central nervous system (CNS). ChEs, both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), are enzymes that play key roles in cholinergic neurotransmission and other physiological functions, such as muscle contraction and detoxification. The objective of this study was to investigate the effects of short and long term exposure to two different doses of DZ on the behavioral performance and activity of ChEs of CNS and peripheral tissues, as well as to study the kinetic parameters of AChE inhibition by DZ, in vitro. Male Swiss adult mice were used for this purpose. The animals were exposed subcutaneously to DZ at doses of 0, 10 or 100 mg/kg for 10 or 30 days. During the last four days of treatment, the animals were submitted to behavioral tasks of open field (OF) and Morris water maze (MWM). On the 11th or 31st day, the animals were euthanized and the cerebral cortex, hippocampus, spleen, heart, stomach, liver, small intestine, skeletal muscle, pancreas, lung and kidney were collected to measure ChEs activity. For the in vitro assays, the sampling was performed similarly. Exposure to DZ for 10 or 30 days did not cause locomotor damage or altered memory, analyzed in the OF and MWM task, respectively. DZ does not alter the activity of cortex and hippocampus ChEs. In peripheral tissues, exposure for 10 days decreased the activity of the stomach bag, and of the BBB in the stomach, rim, lung and plasma. Exposure for 30 days decreased AChE activity of intestine, heart, liver and pancreas; and decreased BBB, intestinal, kidney, liver, lung and pancreas activity. The in vitro results show that an AChE of cerebral origin is insensitive to DZ; while the enzymes of peripheral origin are more sensitive to the compound. It is also possible that DZ is not competitively shaped to perform a heart and pancreas examination and has a mixed-type behavior for stomach and skin disease at the highest concentration tested. The results together may suggest that the absence of behavioral changes may be related to a lack of effects on a cerebral AChE, verified both in vivo and in vitro.