Cadmium (Cd), a highly toxic environmental pollutant, leads to a neurotoxicity and cognitive dysfunction in both animals and humans. In spite of the available in vitro evidence, there is a paucity of literature on the mechanisms by which CdCl2 induced these effects, in vivo. While numerous in vivo studies have shown a protective effect of Quercetin (QUR) against neurodegenerative disease, there is still uncertainty about the safety of such efficiency of QUR due to its low bioavailability.
Therefore, trails to enhance this have shown increased brain accumulation of QUR when administered in conjugation with α-tocopherol. Consequently, this study aimed to investigate the molecular effects of individual and combined administration of QUR and α-tocopherol against CdCl2 induced apoptosis and memory loss in rats. Results of the current study revealed that CdCl2 induced neural apoptosis, spatial memory loss and disturbed brain cholinergic system in mechanisms related to
increased oxidative stress, inhibition of protein phosphatase (PP2A) induced activation of ERK1/2 and JNK and activation of PTEN induced inhibition of Akt/mTOR/S6K1 signaling pathways. As compared to individual effects of QUR or α-tocopherol which were not effective to ameliorate CdCl2 induced apoptosis and cognitive dysfunction, combined administration of both drugs in both control and CdCl2 intoxicated rats could significantly enhance levels of antioxidant defense, improved cognitive dysfunction by enhancing levels of acetylcholine (Ach) and protein levels of CREB and BDNF, and decreased neural apoptosis by upregulating levels of PP2A induced inhibition of ERK1/2 and JNK signaling as well as downregulating expression of PTEN induced activation of Akt/mTOR/S6K1 signaling. In conclusion, only concomitant administration of QUR and α-tocopherol but not their individual use, provide an excellent protective formula against CdCl2 induced neurodegeneration and memory loss.
Key words: ERK1/2; JNK; Akt/m-TOR; Quercetin; α-tocopherol; apoptosis; cognitive dysfunction
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