The Scutellarin Protects Mouse Ovarian Granulosa Cells from ZEA-Induced Injury

BackgroundThe zearalenone (ZEA) contained in the animal grain feeds is produced by Fusarium fungi and this toxin targets ovarian granulosa cells (GCs) to cause reproductive disorders in female animals. Current research on drugs that can rescue ZEA-induced GCs damage is limited. The purpose of this study was to explore the effect of scutellarin (Scu) on ZEA-induced apoptosis of mouse ovarian GCs and its mechanism.ResultsIn one set of experiments, the primary cultured mouse ovarian GCs were co-treated with ZEA and scutellarin for 24 h. The results showed that Scu significantly alleviated ZEA-induced cell damage, restored cell cycle arrest, and inhibited apoptosis by reducing the ratio of cleaved-caspase-3, cleaved-PARP, and Bax/Bcl-2. In other set of experiments, six weeks old mice were intragastrical administered with 40 mg/kg ZEA for 2 h, followed by 100 mg/kg Scu for 3 d. It was shown that Scu inhibited ZEA-induced apoptosis and positive signal expression of cleared-caspase-3 in the ovarian granulosa layer, with the involvement of mitochondrial apoptotic pathway. ConclusionScu attenuated ZEA-induced reproductive toxicity by targeting mouse ovarian GCs, mainly affecting cell cycle phase distribution and apoptosis via mitochondrial apoptotic pathway in vitro and in vivo. These data provide strong evidence that Scu can be further developed as potential new therapeutic drug for preventing or treating reproductive toxicity caused by animal exposure to ZEA found in the grains of animal feeds.