γ-Glutamylcysteine Alleviates t-BHP-Induced Oxidative Damage in NIH/3T3 Fibroblasts by Promoting Nuclear Translocation of Nrf2.

Fibroblasts are essential for tissue repair, but reactive oxygen species (ROS) can impair their function, leading to mitochondrial dysfunction and apoptosis. γ-Glutamylcysteine (γ-GC), a glutathione (GSH) precursor and potent antioxidant, may protect fibroblasts, though its mechanisms in ROS-mediated damage remain unclear. This study examined γ-GC's effects on tert-butyl hydroperoxide (t-BHP)-injured NIH/3T3 fibroblasts. γ-GC effectively reduced ROS levels, restored antioxidant defenses, and preserved mitochondrial function, thereby inhibiting apoptosis. Mechanistically, γ-GC upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) and promoted its nuclear translocation. The Nrf2 inhibitor ML385 confirmed that γ-GC's protective effects were mediated through Nrf2 activation. These results demonstrate that γ-GC, as a direct GSH precursor, not only scavenges ROS but also enhances cellular antioxidant capacity and mitochondrial homeostasis. Its dual role in ROS mitigation and Nrf2 activation highlights γ-GC's therapeutic potential for improving aberrant tissue repair.