Abstract
Benzo(a)pyrene (BaP), a toxic polycyclic aromatic hydrocarbon, is spread in different ways as an environmental pollutant. It has been proposed that BaP can induce toxicity through oxidative stress and apoptosis in vital organs. The present study evaluated the protective effect of melatonin, a circadian hormone of the pineal gland, on BaP-induced neurotoxicity focused on oxidative stress, autophagy, and apoptosis pathways. Thirty male mice in 5 groups were treated daily for 28 consecutive days: (I) control group (BaP and melatonin solvent), (II) BaP (75 mg/kg, orally), (III) and (IV) BaP + melatonin (10 and 20 mg/kg, i.p.), (V) melatonin (20 mg/kg). The oxidative stress markers were determined in the brain. Western blot was conducted for the level of LC3 II/I and Beclin1, as autophagy markers, caspase3 and Bcl2, as apoptosis proteins, and Sirt1 in the brain. The exposure of mice to BaP caused a marked increase in the malondialdehyde (MDA) level and decrease of glutathione (GSH) content in the brain. Furthermore, the Sirt1 level upregulated as well as LC3 II/I, Beclin1, and cleaved caspase3 proteins, while the level of Bcl2 did not change. Melatonin at 20 mg/kg concurrently with BaP restored the BaP alteration in the brain compared with the BaP group. In conclusion, BaP induced brain toxicity via the induction of oxidative stress, apoptosis, and autophagy, whereas melatonin afforded neuroprotection against BaP due to inhibition of these mechanisms.
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This paper was financially supported by the Vice Chancellor of Research, Mashhad University of Medical Sciences, Mashhad, Iran (Grant No. 97181).
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SM and SB wrote the paper and analyzed the data. SB and EZ performed the experiments. GK conceived and designed the experiments. All authors read and approved the manuscript and all data were generated in-house and that no paper mill was used.
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Mehri, S., Barangi, S., Zamiri, E. et al. The protective effect of melatonin on benzo(a)pyrene-induced brain injury: role of apoptosis and autophagy pathways. Naunyn-Schmiedeberg's Arch Pharmacol 393, 2241–2251 (2020). https://doi.org/10.1007/s00210-020-01936-9
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DOI: https://doi.org/10.1007/s00210-020-01936-9