Involvement of paraoxonase [PON] in oxidative stress induced by chlorpyrifos in albino rats

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 Animals were weighed weekly and blood samples were withdrawn after 7, 14, 21 and 28 days from the start of treatment.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. Keywords Organophosphorus insecticides, chlorpyrifos, oxidative stress, Paraoxonase, carboxyl esterase, acetyl cholinesterase, glutathione-s-transferase, reduced glutathione, Malondialdehyde, lipid profile male rats