Protective effect of N-acetylcysteine on Dipentyl phthalate (DPeP) induced cognitive dysfunction and brain oxidative stress in mice

Background: Dipentyl phthalate (DPeP) is a plasticizer compound commonly used in polyvinylchloride plastic to increase their softness and flexibility. They are not bound covalently to the plastic polymers and can therefore leach out into the environment, and have been shown to adversely affect the health of humans and animals. Methods: We investigated the effect of DPeP on the various cognitive parameters and oxidative stress markers in mice. The protective effects of N-acetylcysteine (NAC) on DPeP induced alteration in cognitive behaviour and oxidative stress was also studied. Mice were orally treated with two doses (33 and 100mg/kg ) of DPeP for 28 days. Cognitive functions were assessed using spatial navigation task on Morris water maze (MWM) and Step down latency (SDL) in passive avoidance apparatus. Oxidative stress was assessed by examining the levels of malondialdehyde (MDA), glutathione (GSH), ferric reducing antioxidant power (FRAP) and 8-Hydroxy-deoxyguanosine (8-OH-dG) levels in whole brain of mice. Results: There was a significant increase of latency in spatial navigation task and significant decline in the SDL in passive avoidance apparatus in DPeP  treated group as compared to the control groups. There was also a significant increase in the levels of oxidative stress following DPeP administration as seen with rise in levels of MDA, 8-OH-dG and a fall in GSH and FRAP levels. Conclusion: The present study shows that DPeP adversely affects learning and memory functions in mice by an oxidative stress mediated neuronal damage and these effects were attenuated by pre-treatment with NAC.