<i>Ante-mortem</i> glutathione peroxidase 4 inhibition by RSL3 affects post-mortem meat quality in broiler chickens

1. This study investigated the role of glutathione peroxidase 4 (GPX4), a key regulator of ferroptosis, a form of programmed cell death, in muscle biochemistry and meat quality, utilising broiler chickens whose <i>ante-mortem</i> GPX4 activity was inhibited pharmacologically.2. Male broilers were divided into two groups, each receiving <i>ante-mortem</i> administration of the GPX4 inhibitor, Ras-selective lethal 3 (RSL3), or a vehicle only. After slaughter, breast muscles were collected and stored for 48 h. The expressions of ferroptosis-related genes, glutathione levels, pH, colour and water-holding capacity were evaluated at multiple time points during the storage period.3. The RSL3 treatment decreased the expression of <i>GPX4</i> and ferritin heavy chain 1, which are negative regulators of ferroptosis, while it increased the expression of a ferroptosis accelerator, acyl-CoA synthetase long chain family member 4. The ratio of reduced to oxidised glutathione was significantly decreased in the RSL3 group. The RSL3 treatment decelerated post-mortem pH decline and colour changes, such as a decrease in L* and an increase in a* were observed in the RSL3 group. In addition, the RSL3 group showed increased levels of water-holding capacity.4. These findings suggested that <i>ante-mortem</i> GPX4 activity plays a role in determining meat quality, implying the possible involvement of ferroptosis in the mechanism by which skeletal muscle is converted after slaughter into meat that is eaten.