2,4,6-triiodophenol induces glomerular mesangial cell damage through inflammatory imbalance, oxidative stress...

2,4,6-Triiodophenol (TIP) is a highly toxic iodinated disinfection byproduct that is generated during water disinfection, and TIP is widely detected in drinking water. This study aimed to investigate the nephrotoxicity of TIP and its potential mechanisms.

An in vitro exposure model was constructed by using mouse glomerular mesangial cells (MES-13 cell line). The cytotoxicity of TIP was evaluated via the CCK-8 assay and microscopic morphological observation. The expression of inflammatory cytokines was detected by qRT-PCR and ELISA. Oxidative stress markers, including malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD), were detected using ELISA, and cell apoptosis was analyzed by flow cytometry.

TIP exhibited obvious dose-dependent cytotoxicity in MES-13 cells. Low concentrations of exposure showed no significant cytotoxicity, whereas high concentrations of exposure markedly inhibited cell viability. Moreover, TIP can promote the gene and protein expression of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6). However, while the gene expression of the anti-inflammatory cytokine IL-10 was increased, its protein expression level showed no significant change, suggesting a post-transcriptional regulation or a protein translation delay effect. Further studies revealed that TIP not only overactivates oxidative stress but also induces aberrant apoptotic regulation. This finding indicates that MES-13 cells may respond to TIP-induced damage by regulating oxidative stress and cell apoptosis.

This study firstly demonstrated that TIP can induce glomerular mesangial cell damage through inflammatory imbalance, oxidative stress overactivation, and aberrant apoptosis. Our findings not only provide experimental evidence to elucidate the nephrotoxic mechanisms of TIP but also contribute to establishing relevant strategies for health risk prevention and control.