Antagonistic Effects Of Natural Polyphenols On The Toxicity Of Cadmium

Cadmium has been classified as a classⅡcarcinogen by the International Oncology Agency（IARC）.Clinically,chelating agents are most commonly used to treat patients with Cd poisoning,but there are some disadvantages in the application of chelating agents.For example,during the treatment of chronic Cd poisoning with disodium eodinate,chelating agent-bound Cd accumulates in the kidney,resulting in increasing the content of Cd in the kidney and aggravating nephrotoxicity.Phenolic natural products exist in fruits,vegetables,tea and other plants.Due to their excellently antioxidant activity,phenolic natural products have been used to prevent and treat cancers,eliminate inflammation and treat neurodegenerative diseases.However,the antagonistic effects and mechanism of polyphenolic natural products on Cd toxicity are still unclear.In this study,resveratrol of stilbene,curcumin of phenolic acid and quercetin of flavonoids were used to investigate the antagonism and mechanism of different kinds of natural polyphenols on Cd-induced cytotoxicity and genotoxicity.（1）Antagonistic effect of polyphenols on Cd-induced cytotoxicityBecause the liver,kidney and lung are the main target organs for Cd accumulation,we selected LO₂and HepG2 cells in the liver,A549 and BEAS-2B cells in the lung,786-O cells and HEK-293 cells in the kidney to explore the antagonistic effects of polyphenols on different cell lines.The results showed that the antagonistic efficiency of polyphenols to Cd was different in different target organs.Curcumin had the best effect,followed by resveratrol and quercetin.After that,we verified the changes of apoptosis and the content of lactate dehydrogenase（LDH）in HepG2 cells.It was found that curcumin and resveratrol had obvious antagonistic effects on Cd-induced apoptosis and the increase of LDH.Curcumin had the best antagonistic effect,followed by resveratrol.The cells pretreated with quercetin had no significant protective effect on Cd-induced apoptosis and the increase of lactate dehydrogenase,which was similar to the results of cell survival test.It can be seen that the antagonistic effects of polyphenols on Cd in different cell lines are very different.（2）Protective effects of polyphenols on the genotoxicity caused by CdPhosphorylated histone（γ-H2AX）is a protein involved in the process of DNA repair and is the most sensitive molecule to DNA damage,which is used to screen the genotoxicity of compounds both in vitro and in vivo.In order to explore the protective effect of polyphenols on the genotoxicity induced by Cd,we detected the changes ofγ-H2AX protein content.The results showed that curcumin,resveratrol and quercetin could significantly reduce the increase ofγ-H2AX protein content induced by Cd.These data suggested that polyphenol natural products had a good protective effect on DNA damage caused by Cd.（3）Mechanism of antagonistic effect of polyphenols on Cd toxicityThe purpose of this study was to explore the mechanism of polyphenols against the toxicity of Cd from two aspects of oxidative stress and intracellular accumulation of Cd.The results showed that polyphenols could not only reduce the increase of ROS induced by Cd,but also reduce the accumulation of Cd in cells.Curcumin had the strongest ability to reduce the intracellular accumulation of ROS and Cd,followed by resveratrol and quercetin.In conclusion,polyphenols have protective effects on both genotoxicity and cytotoxicity induced by Cd,and the antagonistic effect on genotoxicity is better than that on cytotoxicity.The antagonistic effect of different kinds of polyphenols on Cd toxicity was different.Curcumin of phenolic acids had the best effect on Cd toxicity,while resveratrol of astragalus and quercetin of flavonoids had the average effect on Cd toxicity.We explored the mechanism of the difference from two aspects:antioxidant and reduction of Cd intracellular accumulation.It provides a new idea to select safe and efficient natural polyphenols for Cd toxicity as an intervention method for Cd detoxification.