Quercetin Alleviates Toxicity Induced by High Levels of Copper in Porcine Follicular Granulosa Cells by Scavenging Reactive Oxygen Species and Improving Mitochondrial Function

SIMPLE SUMMARY: CuSO(4) is a commonly used growth-promoting agent in pig production. It is clear that long-term intake of excess CuSO(4) will damage the reproductive performance of pigs. To better understand the toxic mechanism of CuSO(4) and the alleviating effect of quercetin on it, the oxidative stress level and mitochondrial status of porcine follicular granulosa cells treated with CuSO(4), or quercetin combined with CuSO(4) were investigated in this study. Our results suggest that quercetin could alleviate toxicity induced by high levels of copper in porcine ovarian granulosa cells by scavenging ROS and improving mitochondrial function. ABSTRACT: CuSO(4) is the most commonly used feed additive in pig production at present, but long-term ingestion of excessive copper would lead to chronic copper toxicity. High copper could reduce the reproductive efficiency of sows and seriously affect the development of the pig industry. Quercetin (QUE), a powerful antioxidant, reduces toxicity of a number of heavy metals. Porcine granulosa cells (pGCs) are crucial to the fate of follicle development. The present study found that high concentrations of CuSO(4) induced ROS production, which resulted in decreased mRNA expression of antioxidant-related genes GPX4, CAT, and SOD2 and increased mRNA expression of SOD1, TRX, and HO-1. The protein expression of antioxidant enzymes SOD2 and HO-1 decreased. Moreover, the concentration of MDA increased, the activity of CAT decreased, and the content of GSH decreased. After high copper treatment, the mitochondrial membrane potential (MMP) was decreased and the morphological structure was changed. However, the combined treatment with Quercetin (QUE) reversed these changes, and the level of cellular oxidative stress decreased. Therefore, we conclude that high copper has oxidative toxicity to pGCs, and QUE could remove the ROS induced by high copper, protect mitochondria from oxidative stress damage, and improve the function of pGCs.