Mercuric chloride induced brain toxicity in mice: The protective effects of puerarin‐loaded PLGA nanoparticles

Abstract

AbstractMercury is a toxic, environmentally heavy metal that can cause severe damage to all organs, including the nervous system. The functions of puerarin include antioxidant, anti‐inflammatory, nerve cell repair, regulation of autophagy, and so forth. But because of the limited oral absorption of puerarin, it affects the protective effect on brain tissue. The nano‐encapsulation of Pue can improve its limitation. Therefore, this study investigated the protective effect of Pue drug‐loaded PLGA nanoparticles (Pue‐PLGA‐nps) on brain injury induced by mercuric chloride (HgCl2) in mice. The mice were divided into normal saline (NS) group, HgCl2 (4 mg/kg) group, Pue‐PLGA‐nps (50 mg/kg) group, HgCl2 + Pue (4 mg/kg + 30 mg/kg) group, and HgCl2 + Pue‐PLGA‐nps (4 mg/kg + 50 mg/kg) group. After 28 days of treatment, the mice were observed for behavioral changes, antioxidant capacity, autophagy and inflammatory response, and mercury levels in the brain, blood, and urine were measured. The results showed that HgCl2 toxicity caused learning and memory dysfunction in mice, increased mercury content in brain and blood, and increased serum levels of interleukin (IL‐6), IL‐1β, and tumor necrosis factor‐α in the mice. HgCl2 exposure decreased the activity of T‐AOC, superoxide dismutase, and glutathione peroxidase, and increased the expression of malondialdehyde in the brain of mice. Moreover, the expression levels of TRIM32, toll‐like receptor 4 (TLR4), and LC3 proteins were upregulated. Both Pue and Pue‐PLGA‐nps interventions mitigated the changes caused by HgCl2 exposure, and Pue‐PLGA‐nps further enhanced this effect. Our results suggest that Pue‐PLGA‐nps can ameliorate HgCl2‐induced brain injury and reduce Hg accumulation, which is associated with inhibition of oxidative stress, inflammatory response, and TLR4/TRIM32/LC3 signaling pathway.