Impact of the nitric oxide substrate L-arginine alone and combined with atropine on malathion neuro and hepato-toxicity.

OBJECTIVES

We investigated the impact of the nitric oxide substrate L-arginine on the neuro- and hepato-toxic effects of malathion in rats.

METHODS

Rats were treated intraperitoneally with malathion (150 mg/kg) alone or combined with L-arginine (100, 200 or 400 mg/kg), atropine (2 mg/kg) or L-arginine (200 mg/kg) combined with atropine (2 mg/kg). Rats were euthanized 4 h later, and their brains and livers analyzed for malondialdehyde, nitric oxide (NO), reduced glutathione (GSH), paraoxonase-1 (PON-1). Moreover, butyrylcholinesterase (BChE), interleukin-15 (IL-15) and anti-apoptotic protein B cell/lymphoma-2 (Bcl-2) were determined in brain tissue. Histopatholoy was also performed.

RESULTS

Malathion significantly raised brain NO and malondialdehyde alongside with a notable drop in PON-1 activity and GSH levels relative to the saline control. Brain BChE and Bcl-2 were markedly inhibited whereas IL-15 significantly increased by malathion. In brain, L-arginine treatment resulted in a significantly increased malondialdehyde, decreased GSH, and increased IL-15. A significant decrease in liver malondialdehyde occurred by L-arginine/atropine or atropine. In contrast, L-arginine, L-arginine/atropine or atropine caused a significant decrease in brain and liver NO levels and increased PON-1 activity. Bcl-2 in brain significantly increased by atropine. Malathion induced brain neuronal and liver degeneration showed marked improvement after atropine alone.

CONCLUSIONS

These results indicated that exogenously administered L-arginine did not protect against the neuro- and hepto-toxic effects of malathion. Meanwhile, the ability of atropine to mitigate the deleterious effects of a toxic dose of malathion provides a strong support to the role of excessive stimulation cholinergic pathways in inflicting such damage.