Work

Betaine Inhibits Ferroptosis After Intracerebral Hemorrhage by Activating the Nrf2/HO-1 Pathway

Year: 2026

Type: article

Abstract: Intracerebral hemorrhage (ICH) is a type of stroke with high mortality and disability rates. The hemoglobin and iron ions released by ruptured red blood cells after ICH can induce programmed cell death characterized by lipid peroxide accumulation-a defining feature of ferroptosis-which is one of the key mechanisms for the occurrence and progression of secondary brain injury after ICH. Betaine (BET), a natural amino acid derivative, is known to be an antioxidant, but its protective effect and molecular mechanisms in ICH-induced ferroptosis have not been studied yet. In this study, we investigated the effect of BET intervention on ICH-induced ferroptosis and possible mechanisms in vitro and in vivo, and we evaluated the expression of ferroptosis and oxidative stress molecules through in vivo and in vitro experiments. We analyzed the distribution of nuclear factor E2-related factor 2 (Nrf2) and assessed neurobehavioral function, hematoma volume, and iron content in the brain tissue of mice with ICH. BET upregulates nuclear factor E2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) signaling, reducing long-chain acyl-CoA synthetase 4 (ACSL4), reactive oxygen species (ROS), and malondialdehyde (MDA) while increasing glutathione (GSH) and glutathione peroxidase 4 (GPX4) levels. It also decreases brain iron accumulation, aids hematoma clearance, and protects against ferroptosis and oxidative damage post ICH. Inhibition of Nrf2 with ML385 diminishes BET's neuroprotective effects, highlighting the pathway's importance in BET's mechanism of action. BET boosts antioxidant capacity via the Nrf2/HO-1 pathway; inhibits ferroptosis; reduces oxidative stress, brain edema, and iron accumulation post ICH; and aids hematoma clearance, offering neuroprotection.

Source: Antioxidants

DOI: 10.3390/antiox15010135

Authors: Jie Chen, Xurui Lu, Sunqian Liu, Weiliang Hu, Xiaorong Zhou, Zhifeng Wang

Institutions: Second Affiliated Hospital of Nantong University, Southeast University, Nantong University

Language: English

Topic: Intracerebral and Subarachnoid Hemorrhage Research

Subfield: Neurology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499