An Overview of Hexavalent Chromium-Induced Necroptosis, Pyroptosis, and Ferroptosis
Kurmangaliyeva S. Baktikulova K. Tkachenko V. Seitkhanova B. Shapambayev N. Rakhimzhanova F. Almagambetova A. Kurmangaliyev K.
May 2025Springer
Biological Trace Element Research
2025#203Issue 52619 - 2635 pp.
Heavy metals are common environmental industrial pollutants. Due to anthropogenic activity, chromium, especially its hexavalent form [Cr(VI)], is a widespread environmental contaminant that poses a threat to human health. In this review paper, we summarize the currently reported molecular mechanisms involved in chromium toxicity with a focus on the induction of pro-inflammatory non-apoptotic cell death pathways such as necroptosis, pyroptosis, and ferroptosis. The review highlights the ability of chromium to induce necroptosis, pyroptosis, and ferroptosis revealing the signaling pathways involved. Cr(VI) can induce RIPK1/RIPK3-dependent necroptosis both in vitro and in vivo. Chromium toxicity is associated with pyroptotic NLRP3 inflammasome/caspase-1/gasdermin D-dependent secretion of IL-1β and IL-18. Furthermore, this review emphasizes the role of redox imbalance and intracellular iron accumulation in Cr(VI)-induced ferroptosis. Of note, the crosstalk between the investigated lethal subroutines in chromium-induced toxicity is primarily mediated by reactive oxygen species (ROS), which are suggested to act as a rheostat determining the cell death pathway in cells exposed to chromium. The current study provides novel insights into the pro-inflammatory effects of chromium, since necroptosis, pyroptosis, and ferroptosis affect inflammation owing to their immunogenic properties linked primarily with damage-associated molecular patterns. Inhibition of these non-apoptotic lethal subroutines can be considered a therapeutic strategy to reduce the toxicity of heavy metals, including chromium.
Cancer , Cell death , Ferroptosis , Heavy metals , Necroptosis
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Department of Microbiology, Virology and Immunology, West Kazakhstan Marat Ospanov Medical University, 68 Maresyev St, Aktobe, Kazakhstan
State Institution “Republican Scientific and Practical Centre of Sports, ” 8 Narochanskaya St, Minsk, Belarus
Department of Microbiology, Virology and Immunology, South Kazakhstan Medical Academy, Al-Farabi Sq, Shymkent, Kazakhstan
Department of General Practitioner – 1, Khoja Akhmet Yasawi International Kazakh-Turkish University, 7/7 Baitursynov St, Shymkent, Kazakhstan
Department of Microbiology, NCJSC “Semey Medical University, ” 103 Abay St, Semey, Kazakhstan
Department of Phthisiology and Dermatovenerology, West Kazakhstan Marat Ospanov Medical University, 68 Maresyev St, Aktobe, Kazakhstan
Department of Microbiology
State Institution “Republican Scientific and Practical Centre of Sports
Department of Microbiology
Department of General Practitioner – 1
Department of Microbiology
Department of Phthisiology and Dermatovenerology
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