Characterization of formaldehyde-induced hepatotoxicity based on proteometabolomic analysis

Sanjita Paudel; Hyunchae Sim; Eunjoo Kang; Minseo Kim; Chai Won Park; Ann yae Na; Eun Ki Min; Ki Tae Kim; Wonhwa Lee; Sangkyu Lee

doi:10.1016/j.toxlet.2025.09.003

Characterization of formaldehyde-induced hepatotoxicity based on proteometabolomic analysis

Sanjita Paudel
, Hyunchae Sim
, Eunjoo Kang
, Minseo Kim
, Chai Won Park
, Ann yae Na
, Eun Ki Min
, Ki Tae Kim
, Wonhwa Lee
, Sangkyu Lee

Dept. of Environmental Engineering

Research output: Contribution to journal › Article › peer-review

Abstract

Formaldehyde (FA) is a well-known environmental toxicant used in various industries, including biomedical, agriculture, and textiles, but poses significant health risks. Despite extensive research, the exact hepatotoxic mechanism of FA remains unclear. This study investigated FA-induced liver toxicity through an integrative analysis of proteomics and metabolomics in rat models, identifying 84 differentially expressed proteins and 66 metabolites. Using xMWAS and Reactome software, the study highlighted ferroptosis as a key pathway in FA-induced liver damage. STAT3/HO-1 were identified as crucial protein biomarkers, leading to ferroptosis via lipid peroxide accumulation through iron efflux. Validation through qPCR, western blot, and cell experiments confirmed the involvement of genes like Stat3, Hmox-1, and coagulation-related genes (Fga, Fgb, Fgg, Serpina1, and A2M). This research reveals a novel FA hepatotoxic mechanism involving ferroptosis and complement and coagulation pathways, offering potential for therapeutic interventions.

Original language	English
Pages (from-to)	212-222
Number of pages	11
Journal	Toxicology Letters
Volume	412
DOIs	https://doi.org/10.1016/j.toxlet.2025.09.003
State	Published - Oct 2025

Keywords

Formaldehyde
Hepatotoxicity
Integrative omics
Proteo-metabolomics

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10.1016/j.toxlet.2025.09.003

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title = "Characterization of formaldehyde-induced hepatotoxicity based on proteometabolomic analysis",

abstract = "Formaldehyde (FA) is a well-known environmental toxicant used in various industries, including biomedical, agriculture, and textiles, but poses significant health risks. Despite extensive research, the exact hepatotoxic mechanism of FA remains unclear. This study investigated FA-induced liver toxicity through an integrative analysis of proteomics and metabolomics in rat models, identifying 84 differentially expressed proteins and 66 metabolites. Using xMWAS and Reactome software, the study highlighted ferroptosis as a key pathway in FA-induced liver damage. STAT3/HO-1 were identified as crucial protein biomarkers, leading to ferroptosis via lipid peroxide accumulation through iron efflux. Validation through qPCR, western blot, and cell experiments confirmed the involvement of genes like Stat3, Hmox-1, and coagulation-related genes (Fga, Fgb, Fgg, Serpina1, and A2M). This research reveals a novel FA hepatotoxic mechanism involving ferroptosis and complement and coagulation pathways, offering potential for therapeutic interventions.",

keywords = "Formaldehyde, Hepatotoxicity, Integrative omics, Proteo-metabolomics",

author = "Sanjita Paudel and Hyunchae Sim and Eunjoo Kang and Minseo Kim and Park, \{Chai Won\} and Na, \{Ann yae\} and Min, \{Eun Ki\} and Kim, \{Ki Tae\} and Wonhwa Lee and Sangkyu Lee",

note = "Publisher Copyright: {\textcopyright} 2025",

year = "2025",

month = oct,

doi = "10.1016/j.toxlet.2025.09.003",

language = "English",

volume = "412",

pages = "212--222",

journal = "Toxicology Letters",

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TY - JOUR

T1 - Characterization of formaldehyde-induced hepatotoxicity based on proteometabolomic analysis

AU - Paudel, Sanjita

AU - Sim, Hyunchae

AU - Kang, Eunjoo

AU - Kim, Minseo

AU - Park, Chai Won

AU - Na, Ann yae

AU - Min, Eun Ki

AU - Kim, Ki Tae

AU - Lee, Wonhwa

AU - Lee, Sangkyu

PY - 2025/10

Y1 - 2025/10

N2 - Formaldehyde (FA) is a well-known environmental toxicant used in various industries, including biomedical, agriculture, and textiles, but poses significant health risks. Despite extensive research, the exact hepatotoxic mechanism of FA remains unclear. This study investigated FA-induced liver toxicity through an integrative analysis of proteomics and metabolomics in rat models, identifying 84 differentially expressed proteins and 66 metabolites. Using xMWAS and Reactome software, the study highlighted ferroptosis as a key pathway in FA-induced liver damage. STAT3/HO-1 were identified as crucial protein biomarkers, leading to ferroptosis via lipid peroxide accumulation through iron efflux. Validation through qPCR, western blot, and cell experiments confirmed the involvement of genes like Stat3, Hmox-1, and coagulation-related genes (Fga, Fgb, Fgg, Serpina1, and A2M). This research reveals a novel FA hepatotoxic mechanism involving ferroptosis and complement and coagulation pathways, offering potential for therapeutic interventions.

AB - Formaldehyde (FA) is a well-known environmental toxicant used in various industries, including biomedical, agriculture, and textiles, but poses significant health risks. Despite extensive research, the exact hepatotoxic mechanism of FA remains unclear. This study investigated FA-induced liver toxicity through an integrative analysis of proteomics and metabolomics in rat models, identifying 84 differentially expressed proteins and 66 metabolites. Using xMWAS and Reactome software, the study highlighted ferroptosis as a key pathway in FA-induced liver damage. STAT3/HO-1 were identified as crucial protein biomarkers, leading to ferroptosis via lipid peroxide accumulation through iron efflux. Validation through qPCR, western blot, and cell experiments confirmed the involvement of genes like Stat3, Hmox-1, and coagulation-related genes (Fga, Fgb, Fgg, Serpina1, and A2M). This research reveals a novel FA hepatotoxic mechanism involving ferroptosis and complement and coagulation pathways, offering potential for therapeutic interventions.

KW - Formaldehyde

KW - Hepatotoxicity

KW - Integrative omics

KW - Proteo-metabolomics

UR - https://www.scopus.com/pages/publications/105014957848

U2 - 10.1016/j.toxlet.2025.09.003

DO - 10.1016/j.toxlet.2025.09.003

M3 - Article

C2 - 40907675

AN - SCOPUS:105014957848

SN - 0378-4274

VL - 412

SP - 212

EP - 222

JO - Toxicology Letters

JF - Toxicology Letters

ER -

Characterization of formaldehyde-induced hepatotoxicity based on proteometabolomic analysis

Abstract

Keywords

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