Can mercury and arsenic disrupt antioxidant defenses and cause cellular stress?

Mercury and arsenic can each perturb cellular redox biology through thiol binding, glutathione disruption, and mitochondrial effects. The evidence is strongest for core chemical mechanisms and for arsenic-associated oxidative and mitochondrial stress; real-world impact depends substantially on chemical species, dose, duration, and tissue exposure.

Clinical and human evidence

• Arsenic: Human data link greater urinary arsenic with oxidative DNA damage. A meta-analysis of nine studies found a 41.49% increase in urinary 8-OHdG per 10 μg/g-creatinine increase in urinary arsenic; a repeated-measures cohort of 4,067 adults also found cross-sectional and longitudinal associations.
• Arsenic exposure was associated with lower glutathione in pooled in-vivo evidence (SMD −2.86, 95% CI −4.45 to −1.27), with chronic exposure also linked to lower blood GSH.
• Mercury: Higher blood mercury among seafood consumers has been associated with a lower GSH:GSSG ratio, and miner studies report higher malondialdehyde, consistent with a more oxidized state and lipid peroxidation. These measures are indirect and exposure-specific.

Mechanistic evidence

• Mercury (Hg²⁺ and methylmercury) and trivalent arsenicals—arsenite, MMA(III), and DMA(III)—bind cysteine sulfhydryl groups, including GSH and protein thiols. Pentavalent arsenicals bind protein thiols substantially less strongly.
• Mercury can inhibit glutathione peroxidase through its active-site selenocysteine. Arsenic can bind or consume GSH and impair GPx, glutathione reductase, and GST.
• Arsenic experimentally inhibits mitochondrial respiratory complexes I–IV, reduces ATP, dissipates membrane potential, and raises mitochondrial ROS. Mercury similarly disrupts mitochondrial enzymes and membranes, causing depolarization and impaired ATP production.

Bottom line

• The claim is supported by science. Arsenic has particularly strong evidence for oxidative and mitochondrial stress; mercury has strong evidence for thiol/GSH disruption and moderate evidence for oxidative-mitochondrial effects in human-relevant exposure settings.