283 - Quercetin Antagonizes Tall Fescue Toxicosis-induced Cardiovascular Toxicity in Lamb (Ovis Aries) via Modulating PGC-1α Mediated Mitochondrial Biogenesis

Abstract: Quercetin is a natural flavonoid with a higher antioxidant capacity and anti-inflammatory. Tall fescue [Schedonorus arundinaceus (Schreb.) Dumort; E+] is perennial cool-season grass for grazing livestock in North America. Fescue infected with the endophyte (Neotyphodium coenophialum) produces chemicals toxic to livestock. However, the impact of quercetin on alleviating fescue toxicosis has received only limited attention. The objective of this experiment was to investigate the mitigation effect of quercetin on fescue toxicosis-induced cardiotoxicity of lambs. A total number of 24 Dorper lambs were randomized to four groups (n = 6 per group) and grazed tall fescue seed for 42 days. The results indicated that quercetin treatment alleviated fescue toxicosis induced cardiovascular histopathology injury (Fig 1), inhibited the increased trend of creatine kinase activities, and serum prolactin concentrations (Fig 2). Meanwhile, quercetin mitigated fescue toxicosis-induced cardiovascular oxidative damage by decreasing MDA and H₂O₂ contents, increasing antioxidant enzymes (T-SOD, Cu-Zn SOD, CAT, and T-AOC) activities (Fig 3). Quercetin evidently enhanced fescue toxicosis-induced down-regulation of phase I, II, and II detoxification gene expression to relieve oxidative damage (Fig 4-6). Moreover, quercetin triggered the NF-kB signaling pathway to ameliorate fescue toxicosis-induced cardiovascular inflammation (Fig 7-9). Quercetin attenuated cardiac mitochondrial impaired via Parkin/PINK modulated mediated mitophagy and PGC1-α mediated biogenesis(Fig 10-13). Collectively, our findings demonstrated that quercetin explicated potential protection against fescue toxicosis-induced cardiovascular toxicity.