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Study Ties ALDH2*2 Variant to Severe Liver Injury Through 'Aldehyde Storm' Mechanism

Acute surges of reactive aldehydes overwhelmed glutathione defenses, triggering ferroptosis in knock-in mice.

Overview

  • Osaka Metropolitan University used Aldh2*2 knock-in mice, modeling a common East Asian variant that impairs aldehyde detoxification, and exposed them to allyl alcohol metabolized to acrolein.
  • The exposure produced a rapid rise of multiple aldehydes in blood—an “aldehyde storm”—followed by hepatic accumulation and extensive liver injury.
  • Liver glutathione levels were severely depleted during the surge, driving oxidative stress and iron-dependent cell death consistent with ferroptosis.
  • Researchers said the acrolein dose exceeded smoking exposure, whereas patients on acrolein-generating chemotherapy such as cyclophosphamide may face greater risk.
  • The authors recommend that ALDH2*2 carriers limit aldehyde sources including cigarette and e‑cigarette smoke, support antioxidant defenses through diet, and monitor liver health as follow-up studies assess chronic exposure and cancer links.