Chlorpyrifos-induced alterations in rat brain acetylcholinesterase, lipid peroxidation and ATPases

The effect of chlorpyrifos (O, O'-diethyl-3, 5, 6-trichloro-2-pyridyl phosphorothionate, CPF) exposure on acetylcholinesterase (AChE) activity, lipid peroxidation and different ATPases activities was studied in rats. CPF caused significant inhibition of synaptosomal AChE activity in different regions of brain (fore, mid and hind) and inhibition ranged from 36 to 82% in rats receiving 20-100 mg CPF/kg body wt for 3 days. It also produced oxidative stress, resulting in marked increase in peroxidative damage of membrane lipids in a dose-dependent manner. The levels of malondialdehyde (MDA) and 4-hydroxy-2-nonanal (4-HNE), two major end products of lipid peroxidation were significantly increased in all the regions of brain. Increase in MDA levels was 66%, 117% and 172% in fore brain, 70%, 108% and 170% in mid brain and 40%, 110% and 169% in hind brain of rats given 20, 50 and 100 mg CPF/kg body wt for 3 days. The maximum increase in 4-HNE levels in all the three regions of brain was observed in the animals receiving CPF 100 mg/kg body wt. Na+/K+, Mg2+ and Ca(2+)-ATPases were inhibited to different extents in fore-, mid- and hind brain regions of rats given 20, 50 and 100 mg/kg body wt CPF for 3 days. Highest inhibition in the activity of Na+/K(+)-ATPase observed more than 90% in mid and hind-brain. Mg(2+)-ATPase in hind brain showed inhibition up to 97%. Inhibition in Ca(2+)-ATPase activity was also ranged from 22-94% in synaptosomes at different doses of CPF.