ORIGINAL RESEARCH article

Front. Toxicol.

Sec. In Vitro Toxicology

Volume 7 - 2025 | doi: 10.3389/ftox.2025.1583865

Cadmium Decreases Human Gingival Fibroblast Viability and Induces Pro-Inflammatory Response Associated with Akt and MAPK Pathway Activation

Provisionally accepted
  • 1Faculty of Dentistry, Mahidol University, Bangkok, Thailand
  • 2Chakri Naruebodindra Medical Institute (CNMI), Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Samutprakarn, Thailand

The final, formatted version of the article will be published soon.

Smoking and particulate matter 2.5 (PM2.5) expose millions to cadmium (Cd), a toxic heavy metal linked to pro-inflammatory responses, oxidative stress, and disease pathogenesis. In the oral cavity, chronic Cd exposure contributes to the progression of periodontal diseases and oral cancers. However, the direct effect of Cd on oral tissues and the underlying mechanisms remains unclear. This study explored the impact of environmentally relevant concentrations of Cd on human gingival fibroblasts (HGFs) by evaluating cell viability, pro-inflammatory cytokine secretion (IL-6 and IL-8), COX-2 expression, and the activation of key signaling pathways: Akt, ERK1/2, and JNK. Cd exposure significantly reduced HGF viability, elevated IL-6 and IL-8 secretion, and upregulated COX-2 expression. These effects were attenuated by inhibitors targeting Akt, ERK1/2, and JNK pathways. By integrating cytokine profiling, COX-2 expression, and inhibitor-based pathway analysis, our study provides mechanistic insights into how low-level Cd exposure triggers early inflammatory responses in gingival fibroblasts. Our findings reveal that Cd exerts pro-inflammatory and cytotoxic effects on HGFs, which may play a role as one of the factors in the pathogenesis of smoking-related oral diseases. Targeting Akt, ERK1/2, and JNK signaling pathways could offer therapeutic strategies to attenuate Cd-induced oral pro-inflammatory responses and tissue damage.

Keywords: cadmium1, fibroblasts2, cyclooxygenase3, interleukin-64, interleukin-85

Received: 26 Feb 2025; Accepted: 08 Jul 2025.

Copyright: © 2025 Parakaw, Srihirun, Sibmooh, Ruangsawasdi, Khemawoot and Vivithanaporn. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Pornpun Vivithanaporn, Chakri Naruebodindra Medical Institute (CNMI), Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Samutprakarn, 10540, Thailand

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