2. ENVIRONMENTAL ChEMISTRy & TEChNOLOGy 2.1. Lectures

Chem. Listy, 102, s265–s1311 (2008) Environmental Chemistry & Technology
are not only scavengers and alarm cells but they also have
important functions to occupy key positions in every kind of
immune response: production of antibodies, induction of cell
immune reactions, development of immunologic memory
and tolerability, thus correctly being named “dispatcher
cells”. In our experiments, the functional activity of mouse
macrophages was activated under intoxication with OP at
10 –4 mg kg –1 (Fig. 1.). Activation of phagocytes affected by
low doses of OP leads to production of ROS (hydrogen peroxide,
superoxide anion, singlet oxygen and hydroxyl anions),
which cause modification of tissue and serum proteins and
lipids to further cause their obtaining of antigenic properties.
Thus, activation of phagocytes is an autocatalytic process and
can lead to formation of the vicious circle. On the other hand,
absence of macrophages’ activation under exposure to large
doses of OP indicates a suppression of antigen-presenting
function of these cells; it is also known that chemical agents
inhibiting this function in most cases cause suppression of
immune response 16 .
The animals’ immune status was further tested with low
angle light scattering technique and studies of functional activity
of blood platelets. Besides of a leading role in haemostasis,
blood platelets play also an important role in immune
reactions being a mediator between these two physiologic
systems 17,18 . For the expense of binding with C1q receptor,
the platelets can adhere to endothelium of capillaries, where
local interaction of platelets with activating agents can take
place 19,20 .
Peroral chronic administration of DFP and paraoxon to
laboratory animals for 3 months with the following examination
at 2, 4 and 5 months after cessation of the intoxication
demonstrated that in both cases a pronounced disturbance of
the functional activity of platelets was observed, followed by
a prolonged period of recovery of kinetic parameters of platelet
aggregation (Fig. 2.). In 3 months of chronic intoxication
with DFP a marked increase of EC 50 was registered, similar
to the case with Russian VX 21 . In contrast to DFP and RVX,
paraoxon did not have a visible effect on sensitivity of platelets,
but affected the maximal velocity of aggregation to the
greater extent.
Investigation of blood vessel endothelium revealed that
s298
Fig. 3. Relative excess over control (100 %) of the blood vessel
contracting force in 3 months of intoxication with DFP and
paraoxon at doses 10 –2 and 10 –4 mg kg –1 (carbachol was administered
at the background of pre-constriction with norepinephrine)
under chronic intoxication with OP an inhibition of endothelium-dependent
relaxation occurs with both DFP and paraoxon,
though the former was more potent at the same doses
(Fig. 3.). Moreover, the level of pre-constriction with epinephrine
under exposure to DFP was significantly different
from that observed under exposure to paraoxon. So not only
the level of relaxation following pre-constriction did change
but also the background tonus of blood vessels and dynamics
of the pre-constriction per se. In 2 months after cessation of
the intoxication, inhibition of the endothelial function was
nevertheless rather pronounced in both groups of rats that were
exposed to DFP and paraoxon at 10 –2 mg kg –1 . In 5 months,
there were significant changes only in rats exposed to DFP,
being at the same level in both groups of intoxicated rats
administered to DFP at doses 10 –4 and 10 –2 mg kg –1 .
Conclusions
Esterases of various geneses, localization and functional
specialization should be molecular targets for OP.
Fig. 2. Relative changes of the medium effective concentration of activator (EC50) and maximal velocity of platelet aggregation
(umax) after peroral administration of DFP (A) and paraoxon (b) at doses 1 × 10 –2 (max) and 1 × 10 –4 (min) mg kg –1 : after 3 months of
intoxication, then at 2, 4 and 5 months of the “recovery period”; (# – Р < 0.1; * Р < 0.05)