Inflammasome/NF-κB translocation inhibition via PPARγ agonist mitigates inorganic mercury induced nephrotoxicity

Mercury (Hg) pollution poses global human health and environmental risks. However, still knowledge gaps exist on both exposures and health effects. Here, we combined transcriptome sequencing technique to further investigate the specific mechanisms of inorganic Hg toxicity in the kidney. Strikingly, transcriptomic analysis revealed that 4174 unigenes (including 2646 upregulated and 1528 downregulated unigenes) were differentially expressed under acute HgCl₂ (5 mg/kg) exposure in the kidney. Additionally, we observed that HgCl₂ selectively induced tumor necrosis factor superfamily (TNFSF) to participate in renal damage, which was consistent with the high-throughput sequencing data. The phenomenon is accompanied by NLRP3 inflammasome and NF-κB signal activation in the kidney. Simultaneously, ELISA results shown that TNF-α, IL-1β and IL-6 concentrations in the kidney were significant increased. KEGG enrichment analysis showed that peroxisome proliferators-activated receptors (PPAR) signaling pathway might be vital toxic mechanism of Hg in the kidney. Then, our data showed that PPARγ agonist (GW 1929) attenuated HgCl₂ (15 μg/ml)-induced apoptosis and NLRP3 inflammasome activation via decreasing translocation of NF-κB and increasing Bcl2 levels in vitro. Along with this, we demonstrated that PPARγ antagonists (GW9662) effectively aggravated HgCl₂-induced nephrotoxicity. Overall, our results suggested that PPARγ signaling pathway is considered to be a protective mechanism to combat against HgCl₂-triggered NLRP3 inflammasome activation and apoptosis.