Hyperoside Attenuates Zearalenone-induced spleen injury by suppressing oxidative stress and inhibiting apoptosis in mice

Zearalenone (ZEA) is a ubiquitous mycotoxin contaminant that causes immune toxicity, apoptosis, and oxidative stress in animals. Hyperoside (Hyp) is a flavonol glycoside compound with antioxidant and anti-apoptotic properties. However, the potential of Hyp to prevent ZEA-induced spleen injury remains unknown. To evaluate the chemoprotective effect of Hyp against ZEA-induced spleen injury, 60 male Kunming mice were randomly assigned into five groups. The first two groups were orally treated with ZEA (40 mg/kg) for 30 days, and combined with Hyp (0, 100 mg/kg) treatment. The other three groups are orally treated with normal saline, olive oil, or Hyp (100 mg/kg) for 30 days. Hyperoside had an inhibitory effect against ZEA-induced spleen lesions. In addition, Hyp significantly increased the activity of antioxidant enzymes [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT)], the total antioxidant capacity (T-AOC), and significantly reduced the malondialdehyde (MDA) content reducing ZEA-induced oxidative stress in the spleen. Moreover, the translation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target genes (CAT, NQO1, SOD1, GSS, GCLM, and GCLC) were ameliorated using co-therapy with Hyp before treatment with ZEA. Hyperoside also significantly inhibited the translation and expression of apoptotic genes (caspase3, casepase9, Bax, Bcl-2) and the production of apoptotic bodies induced by ZEA in the spleen. In conclusion, the findings revealed that Hyp inhibited ZEA-induced spleen injury through its antioxidant and anti-apoptotic effects. Thus, it provides a new treatment option for immune system diseases caused by ZEA.