ABSTRACT
Organophosphorus insecticides (OPs) exert their toxic effect through
inhibition of acetylcholinesterase (AchE). In addition, accumulated evidences
indicated that oxidative stress involved in OPs neurotoxicity and cytotoxicity.
However, the mechanism underlay OPs induces oxidative stress still so far
unclear. Recent reports were focused on the role of paraoxonase (PON), the
HDL-associated A-esterase, in the degradation of the oxon form of the
organophosphate. This enzyme, which known to play a critical role in OPs
metabolism has a vital role in preventing both LDL and HDL from
Peroxidation. Based on the previous observation we propose that the interaction
of OPs with PON is the key step in initiating lipid Peroxidation and oxidative
stress. To test this suggestion, chlorpyrifos (CPF) was orally gavaged at dose
levels of 3, 6, and 12 mg/Kg/day to adult male albino rats for 28 consecutive
days. Animals were weighed weekly and blood samples were withdrawn after 7,
14, 21 and 28 days from the start of treatment. At the end of the experiment,
animals were sacrificed and organs were weighed. The brain and the liver were
frozen and kept till the biochemical analysis. Malondialdehyde (MDA), reduced
glutathione (GSH), triglyceride (TG), total cholesterol, HDL-cholesterol and
total protein level were determined. Also, PON, carboxyl esterase (CE),
acetylcholinesterase (AchE), and glutathione-S-transferase (GST) activity were
determined. In addition, PON and CE isozymes were separated on Native-PAGE
electrophoresis. Results indicated that CPF produced constant and dose
dependent inhibition in both plasma ChE and liver ChE whereas brain AchE
was weakly affected. A pattern of adaptation was observed in plasma CE. Brain
CE was the most affected, whereas, plasma PON did not affected by (CPF)
treatment. Brain PON seemed to be highly susceptible and the effect was dose
dependent. The same pattern was observed with AE. The native PAGE
confirmed the biochemical determinations. Treatment also increased plasma
MDA. GSH levels in blood, liver and brain were increased whereas, GST
activity increased only in plasma. The cholesterol and triglyceride levels
increased, whereas, HDL level didn't affect by treatment. The analysis of
correlation also showed significant correlation between PON and MDA in brain
and liver. These results support the suggestion that OPs interfere with the
antioxidant system. In addition, it was clear that animals were developed an
adaptation mechanism as a result of repetition chlorpyrifos treatment and more
work should be offer to clear the role of PON in oxidative stress induced by OPs