Occurrence of halonaphthoquinone disinfection byproducts in Shanghai’s drinking water and the hepatotoxic effects on lipid accumulation

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Introduction In recent years, aromatic disinfection by-products (DBPs) have attracted widespread concern due to their elevated concentration and significant toxicity. Recent studies have identified a new class of DBPs, halonaphthoquinones (HNQs), during drinking water disinfection processes, which exhibit both high occurrence levels and considerable toxicological risks. Methods This study established a liquid–liquid extraction coupled with HPLC-MS/MS method to determine HNQs levels in drinking water. In July 2024, source and finished water samples were collected from three drinking water treatment plants (Plants A, B, and C) in Shanghai, which source their water from the Q and J reservoirs. A total of 9 source and 9 finished water samples were collected in each plant. Based on the HNQs concentrations detected in finished water, the effects of mixed HNQs exposure on lipid accumulation in HepG2 human hepatoma cell line in vitro were investigated. Results In finished water, MCNQ showed the highest levels, averaging 8.7–13.05 ng/L and peaking at Plant A (13.05 ng/L, p < 0.05). Followed by MBNQ, with a mean range of 1.37–13.89 ng/L and a peak at Plant B (13.89 ng/L, p < 0.05). Combined exposure to HNQs in drinking water can induce lipid accumulation in HepG2 cells. Under HF culture conditions, HepG2 cells exhibited lipid accumulation even at shorter exposure time and lower concentrations of HNQs, suggesting that HF and HNQs may act synergistically to promote hepatocytic lipid accumulation. Mixed exposure to HNQs can induce oxidative stress in HepG2 cells, possibly by inhibition of IPMK/AMPK/SIRT1/PGC-1α pathway genes expression, which may reduce mitophagic clearance capacity, thereby disrupting the cellular redox balance and promoting lipid accumulation. Discussion These results suggest that HNQs may be important risk factors for metabolic dysfunction-associated fatty liver disease (MAFLD), and further observation and validation of the impact of HNQs on MAFLD are needed in the future.

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