Abstract
Due to its ability to cross blood brain barrier and placenta, dibutyl phthalate (di-n-butyl phthalate, DBP) is expected to cause severe side effects to the central nervous system of animals and humans. A little data is available about the potential DBP neurotoxicity; therefore, this work was designed to investigate the brain tissue injury induced by DBP exposure. Forty Wister albino rats were allocated randomly into 4 groups (10 rats each). Group 1 served as control and the rats administered with physiological saline (0.9% NaCl) orally for 12 weeks. Groups 2, 3 and 4 were orally treated with DPB (100, 250 and 500 mg/kg) respectively for 12 weeks. DBP-intoxicated rats showed a disturbance in the oxidative status in cerebral cortex, striatum and brainstem, as represented by the elevated oxidants [malondialdehyde (MDA), nitric oxide (NO), 8-hydroxy-2-deoxyguanosine (8-OHdG)] and the decreased antioxidant molecules [reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR)]. DBP also enhanced a pro-inflammatory state through increasing the release of tumor necrosis factor- α (TNF-α) and interleukin-1β (IL-1β). The increase of these cytokines was associated with the increase of pro-apoptotic proteins [Bcl-2 associated X protein (Bax) and caspase-3] and the decrease of the anti-apoptotic protein, B cell lymphoma 2 (Bcl-2). In addition, the levels of norepinephrine (NE), dopamine (DA) and acetylcholine esterase (AChE) activity were decreased. This was accompanied by the alterations in the major excitatory and inhibitory amino acids neurotransmitters levels. The present findings indicated that DBP could exert its neuronal damage through oxidative stress, DNA oxidation, neuroinflammation, activation of apoptotic proteins and altering the monoaminergic, cholinergic and amino acids transmission.
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Kassab, R.B., Lokman, M.S. & Essawy, E.A. Neurochemical alterations following the exposure to di-n-butyl phthalate in rats. Metab Brain Dis 34, 235–244 (2019). https://doi.org/10.1007/s11011-018-0341-0
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DOI: https://doi.org/10.1007/s11011-018-0341-0