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

## TL;DR

γ-Glutamylcysteine protects fibroblasts from oxidative damage by boosting antioxidant defenses and promoting Nrf2 activity.

## Contribution

This study reveals γ-Glutamylcysteine's novel dual role in reducing ROS and activating Nrf2 to protect fibroblasts.

## Key findings

- γ-Glutamylcysteine reduces ROS levels and restores antioxidant defenses in NIH/3T3 fibroblasts.
- γ-Glutamylcysteine preserves mitochondrial function and prevents apoptosis via Nrf2 activation.
- Nrf2 inhibition confirms γ-Glutamylcysteine's protective effects depend on Nrf2 nuclear translocation.

## Abstract

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.

γ‐Glutamylcysteine (γ‐GC) reduces reactive oxygen species (ROS) levels in NIH/3T3 fibroblasts via modulation of the intracellular antioxidant system, and mitigates ROS‐induced mitochondrial membrane potential collapse and mitochondrial dysfunction in these cells. γ‐GC further alleviates ROS‐mediated apoptosis in NIH/3T3 fibroblasts. These protective effects of γ‐GC are dependent on its facilitation of Nrf2 nuclear translocation in NIH/3T3 fibroblasts.