Sulforaphane Alleviates PACS 2-Mediated Oxidative Stress Damage in Porcine Endometrial Stromal Cells Induced by Zearalenone.

Abstract

Zearalenone (ZEA) is commonly found in crops and feed, with a high detection rate and concentration. This substance adversely affects reproduction and development, with particularly noticeable effects on pigs. Given these detrimental effects, there is an urgent need to identify effective protective agents against ZEA toxicity. Sulforaphane (SFN) has emerged as a promising candidate owing to its widely acknowledged antioxidant, anti-inflammatory, and detoxifying properties. This study elucidates ZEA's mechanism of oxidative injury in porcine endometrial stromal cells (ESCs) via mitochondrial-associated membrane (MAM) disruption and demonstrates SFN's protective role. ZEA disrupts the structural integrity and functional dynamics of mitochondrial-associated membranes (MAM) by downregulating PACS 2, leading to elevated intracellular Ca2+ levels (P < 0.01), increased ROS generation (P < 0.01), MDA accumulation (P < 0.01), and suppressed antioxidant enzyme activity (P < 0.01). SFN (10 μM) or the overexpression of PACS 2 can reduce the toxic damage caused by ZEA (45 μM). This study highlights the mechanism by which ZEA causes oxidative damage in porcine cells through mitochondrial membrane disruption and showcases SFN's protective effects, opening up possibilities for broader applications against ZEA toxicity.