Alleviation of Pb2+ pollution-induced oxidative stress and toxicity in microglial cells and zebrafish larvae by chicoric acid.

Pb²⁺ pollution and poisoning are serious environmental and pharmacological concerns. The World Health Organization reported that Pb has resulted in 540,000 deaths in 2016 alone. Therefore, effective drugs or supplements that can alleviate or offset Pb²⁺-induced toxicity are badly needed. Through screening biocompatible natural compounds, we discovered that chicoric acid exhibited potent protective activities against Pb²⁺-induced toxicity both in BV-2 microglial cells and in zebrafish from the first days of development. Chicoric acid was able to reduce Pb²⁺-induced increases in levels of reactive oxygen species and tumor necrosis factor alpha, restoring the cell cycle in BV-2 cells. In the zebrafish model, chicoric acid significantly alleviated the Pb²⁺-induced serious mortality and malformation of zebrafish larvae in a concentration-dependent manner. These protective activities of chicoric acid were mainly from its alleviation of Pb²⁺-induced dysregulation of oxidative response pathways, including key genes such as Aox1, Gclm, Hmox1, Nqo1, Scd1, and Srxn1, as well as HO-1 protein. Since Pb²⁺ is difficult to be completely eliminated from the body and chelating agents may cause serious adverse effects, chicoric acid is likely a potential supplement therapy, in addition to current clinical practices.