Institutes of Agricultural Science and Technology Development, Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, P. R. China.
College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, P. R. China.
Environ Toxicol. 2022 Apr;37(4):720-729. doi: 10.1002/tox.23437. Epub 2021 Dec 13.
Autophagy is a regulatory mechanism involved in cadmium (Cd)-induced bone toxicity and is suppressed by various stimuli, including oxidative stress. Puerarin is an isoflavonoid compound isolated from Pueraria, a plant used in traditional Chinese medicine. The underlying mechanisms of action of puerarin remain unclear. The objective of this study was to explore the mitigating effects of puerarin on cadmium-induced oxidative damage in the bones of rats. Cadmium exposure increased oxidative damage in rat bones; this was markedly decreased by puerarin treatment, as demonstrated by changes in the activity of antioxidative enzymes. Cadmium-induced blockage of the expression of key bone regulatory proteins, autophagy-related markers, and signaling molecules was also alleviated by puerarin treatment. Additionally, cadmium reduced expression of the autophagic protein Rab7 and of late endosomal/lysosomal adaptor and MAPK and mTOR activator 1 (LAMTOR1); the decrease in these proteins was not restored by puerarin treatment. We speculate that puerarin relieves the inhibition of fusion of autophagosomes with lysosomes that is induced by cadmium; however, this specific effect of puerarin and downstream effects on bone regulatory mechanisms require further investigation. In conclusion, puerarin alleviates cadmium-induced oxidative damage in the bones of rats by attenuating autophagy, which is likely associated with the antioxidant activity of puerarin.
自噬是一种参与镉(Cd)诱导的骨毒性的调节机制,受到各种刺激的抑制,包括氧化应激。葛根素是从葛根中分离出来的一种异黄酮化合物,葛根是一种用于传统中药的植物。葛根素的作用机制尚不清楚。本研究旨在探讨葛根素对镉诱导的大鼠骨骼氧化损伤的缓解作用。镉暴露增加了大鼠骨骼的氧化损伤;葛根素处理明显减少了这种损伤,这可以通过抗氧化酶活性的变化来证明。镉诱导的关键骨调节蛋白、自噬相关标志物和信号分子的表达受阻也被葛根素处理所缓解。此外,镉降低了自噬蛋白 Rab7 和晚期内体/溶酶体衔接物和 MAPK 和 mTOR 激活物 1(LAMTOR1)的表达;这些蛋白的减少不能通过葛根素处理来恢复。我们推测,葛根素缓解了镉诱导的自噬体与溶酶体融合的抑制;然而,葛根素的这种特定作用及其对骨调节机制的下游影响需要进一步研究。总之,葛根素通过减弱自噬来缓解镉诱导的大鼠骨骼氧化损伤,这可能与葛根素的抗氧化活性有关。