Epigenetic reprogramming in cadmium-associated liver injury: Evidence, mechanistic insights, and therapeutic perspectives

IF 4.6 3区环境科学与生态学 Q2 ENVIRONMENTAL SCIENCES

Environmental toxicology and pharmacology Pub Date : 2026-10-01 Epub Date: 2026-09-26 DOI:10.1016/j.etap.2026.105178

Xing Zhang, Na Liu, Jie Zhou

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Abstract

Chronic cadmium (Cd) exposure is associated with adverse liver outcomes, including metabolic dysfunction-associated steatotic liver disease (MASLD), inflammation, and fibrosis, yet the mechanisms underlying persistent hepatic injury remain incompletely resolved. This review critically examines population-based and experimental evidence for Cd-associated epigenetic alterations, focusing on DNA methylation, histone modifications, N⁶-methyladenosine (m⁶A) RNA modification, and non-coding RNA regulation, and evaluates the extent to which these changes represent epigenetic dysregulation or remodeling versus relatively durable and functionally consequential reprogramming. Evidence is interpreted according to study design and level of functional validation. Current findings support context-dependent, model-specific roles for selected epigenetic regulators, with functional convergence on metabolic dysfunction, oxidative stress, inflammation, cell-death pathways, and fibrogenic activation, rather than a unified causal epigenetic program in humans. We further discuss cross-layer interactions, cell-type heterogeneity, emerging preclinical intervention strategies, and translational barriers, highlighting the need for longitudinal human studies, cell-resolved multi-omics, and target-specific functional validation.

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来源期刊

Environmental toxicology and pharmacology 医学-毒理学

CiteScore

7.00

自引率

4.70%

发文量

185

审稿时长

34 days

期刊介绍： Environmental Toxicology and Pharmacology publishes the results of studies concerning toxic and pharmacological effects of (human and veterinary) drugs and of environmental contaminants in animals and man. Areas of special interest are: molecular mechanisms of toxicity, biotransformation and toxicokinetics (including toxicokinetic modelling), molecular, biochemical and physiological mechanisms explaining differences in sensitivity between species and individuals, the characterisation of pathophysiological models and mechanisms involved in the development of effects and the identification of biological markers that can be used to study exposure and effects in man and animals. In addition to full length papers, short communications, full-length reviews and mini-reviews, Environmental Toxicology and Pharmacology will publish in depth assessments of special problem areas. The latter publications may exceed the length of a full length paper three to fourfold. A basic requirement is that the assessments are made under the auspices of international groups of leading experts in the fields concerned. The information examined may either consist of data that were already published, or of new data that were obtained within the framework of collaborative research programmes. Provision is also made for the acceptance of minireviews on (classes of) compounds, toxicities or mechanisms, debating recent advances in rapidly developing fields that fall within the scope of the journal.