Resveratrol ameliorates disorders of mitochondrial biogenesis and mitophagy in rats continuously exposed to benzo(a)pyrene from embryonic development through adolescence.

ABSTRACT

Exposure to benzo(a)pyrene (BaP) is associated with poor neurodevelopment in children and memory impairment in adults. Previous research has demonstrated that mitochondrial damage plays an important role in BaP-induced neurotoxicity. Of interest, increasing evidence has suggested that resveratrol (RSV) can alleviate nerve cell damage, however the exact mechanisms of biological activity in mitochondria are not fully understood. In the current study, Wistar rats were exposed to BaP (1, 2, 4 mg/kg) and/or RSV (15, 30 mg/kg) during embryonic development and adolescence, and learning and memory ability, mitochondrial damage, and the expression of proteins associated with mitochondrial biogenesis and mitophagy were evaluated. These studies indicated that 2 and 4 mg/kg BaP could induce disorders of mitochondrial biogenesis and mitophagy, which leads to abnormal nerve cell development. However, pretreatment with 30 mg/kg RSV alleviated cell damage and the disorder of mitochondrial biogenesis by activating the AMPK/PGC-1α signaling pathway and promoting mitophagy. These findings suggested that RSV had utility in promoting mitochondrial homeostasis against BaP-induced nerve cell damage in the hippocampus of rats.