Protective effect of rutin on ferroptosis‐induced oxidative stress in aging laying hens through Nrf2/HO‐1 signaling

Abstract

Oxidative stress is a major cause of ovarian aging and follicular atresia. There is growing evidence that showed potential roles of rutin in antidiabetic, anti‐inflammatory, antitumor, antibacterial and antioxidant, although it is yet unclear what the underlying mechanism is. Here, we looked into the potential effects of rutin on oxidative stress in the prehierarchical small white follicles (SWFs) from 580‐day‐old (D580) laying chickens. According to the findings, aging D580 layer ferroptosis was much higher than it was for laying hens during the peak period (280‐day‐old, D280). In both naturally aged and d‐gal‐induced chicken SWFs, rutin treatment concurrently boosted cell proliferation and prevented apoptosis. In addition, rutin inhibited the increased ferroptosis in aging hens. Meanwhile, rutin markedly suppressed the elevated ferroptosis and descending antioxidant capacity of D280‐culture‐SWFs from chicken elicited by d‐gal. Rutin's activation of the Nrf2/HO‐1 pathway hastened the SWFs' verbal battle with oxidative damage and reduced ferroptosis. Furthermore, activation of the ferroptosis signal increased the oxidative damage in SWFs. In conclusion, rutin alleviated oxidative stress that was induced by ferroptosis in aging chicken SWFs through Nrf2/HO‐1 pathway. These findings point to a novel mechanism by which rutin protects SWFs from oxidative stress by suppressing ferroptosis, which is presumably a fresh approach to slowing ovarian aging in laying hens.

Positive effects of rutin on female reproduction

“…Culture of sheep ovarian follicles with rutin increased their morphological quality, although it did not affect their number, viability, growth and development (Lins et al., 2017). Administration of rutin to aging hens prevented the atresia of their ovarian follicles (Wu et al., 2023).…”

“…The stimulatory and protective effect of rutin on rat (Jahan et al., 2016; Nayki et al., 2018), mice (Lins et al., 2017, 2020) and chicken (Wu et al., 2023) folliculogenesis was associated with an increase of antioxidant and mitochondrial activity and a decrease in reactive oxygen species in ovarian follicles. The toxic influence of rutin on cultured cancer cells was associated with its antioxidant effect (de Araújo et al., 2013; Wu et al., 2023). It indicates that rutin effect on ovarian follicle development and human ovarian cancer cells could be mediated by its antioxidative action.…”

“…There is a limited number of evidence for direct action of rutin on viability in ovarian cells, whilst rutin exerted the opposite effects on (Sirotkin, Záhoranska, et al, 2020). Administration of rutin promoted proliferation and suppressed apoptosis and ferroptosis in chicken ovarian cells (Wu et al, 2023).…”

Natural Flavonoids and Ferroptosis: Potential Therapeutic Opportunities for Human Diseases

“…Furthermore, fisetin promoted the expression of FTH1 and HO-1 via activating the SIRT1/NRF2 pathway, which could protect against doxorubicin-induced cardiotoxicity by inhibiting ferroptosis . Analogously, rutin suppressed ferroptosis in small white follicles by regulating the NRF2/HO-1 pathway, thereby improving ovarian aging in laying hens . Galangin, mainly derived from the rhizome of Alpinis officinarum , could protect mouse liver from I/R injury .…”

“…108 Analogously, rutin suppressed ferroptosis in small white follicles by regulating the NRF2/HO-1 pathway, thereby improving ovarian aging in laying hens. 109 Galangin, mainly derived from the rhizome of Alpinis of ficinarum, could protect mouse liver from I/R injury. 110 The levels of phosphoinositide 3-kinase (PI3K), phosphorylated protein kinase B (p-AKT), phosphorylated cAMP response elementbinding protein (p-CREB), and GPX4 were decreased in RSL3-induced HT1080 cells, while galangin treatment restored the levels of these proteins.…”