Abstract

Cadmium (Cd) is a potential pathogenic factor in the nervous system associated with various neurodegenerative disorders. Puerarin (Pur) is an isoflavone purified from the Chinese medical herb, kudzu root, and exhibits antioxidant and antiapoptotic properties in the brain. In this study, the detailed mechanisms underlying the neuroprotective potential of Pur against Cd-induced neuronal injury was evaluated for the first time in vivo in a rat model and in vitro using primary rat cerebral cortical neurons. The results of the in vivo experiments showed that Pur ameliorated Cd-induced neuronal injury, reduced Cd levels in the cerebral cortices, and stimulated Cd excretion in Cd-treated rats. We also observed that the administration of Pur rescued Cd-induced oxidative stress, and attenuated Cd-induced apoptosis by concomitantly suppressing both the Fas/FasL and mitochondrial pathways in the cerebral cortical neurons of rats both in vivo and in vitro. Our results demonstrate that Pur exerted its neuroprotective effects by stimulating Cd excretion, ameliorating Cd-induced oxidative stress and apoptosis in rat cerebral cortical neurons.

Highlights

  • Cadmium (Cd) is an extremely toxic metal pollutant in the environment, which is well known for its occupational health risks

  • To investigate neuroprotective effects of Pur, we evaluated the histological changes in the cerebral cortex by Hematoxylin and Eosin (H&E) staining (Figure 1A)

  • Our results provide the first evidence that Pur exerted its neuroprotective effects by stimulating Cd excretion, ameliorating Cd-induced oxidative stress and apoptosis in rat cerebral cortical neurons

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Summary

Introduction

Cadmium (Cd) is an extremely toxic metal pollutant in the environment, which is well known for its occupational health risks. Cd is associated with toxic effects at extremely low doses and has a long biological half-life Growing evidence has shown that Cd exerts its toxic effects on the liver [2], kidney [3], testis [4], bone [5]. Cd is a potent neurotoxicant that can penetrate the blood brain barrier (BBB) to enter the brain and neurons [7,8]. Based on published reports and our previous observations, Cd induces neurotoxicity via promoting oxidative stress, apoptosis, and autophagy [6,9,10]. It is necessary to identify a novel therapeutic target and strategy to control Cd-induced neuronal injury

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