Hesperidin Intervenes In The Decabromodiphenyl Ether-induced Intestinal And Reproductive Toxicity

Polybrominated diphenyl ethers(PBDEs)are a class of brominated flame retardants.They are widely used in electrical equipment,textile,and food packaging.PBDEs have been shown to induce liver,reproductive,neurological,and thyroid toxicity.As persistent organic pollutants,PBDEs have the characteristics of persistent toxicity and bioaccumulation,which pose a potential threat to human health.Decabromodiphenyl ether(PBDE-209)is one of the PBDEs’ most widely used homologs.This paper aims to explore the intestinal toxicity and reproductive toxicity mechanism induced by PBDE-209 and the effect of hesperidin intervention on the toxicity of PBDE-209.The main contents and results of the research are as follows:First of all,we explored the potential toxicity mechanisms of PBDE-209 in vivo and in vitro.We investigated the effects of PBDE-209 on intestinal oxidative stress and tissue structure in mice and the mechanism of in vitro cytotoxicity.Caco-2 cells were treated with different concentrations of PBDE-209(1,5,and 25 μmol/L)for 24 and 48 h.We determined the cell viability,reactive oxygen species(ROS)levels,mitochondrial parameters,and associated m RNA expression levels.The results showed that PBDE-209 significantly damaged the colon tissue of mice,increased the content of the oxidative stress biomarker malondialdehyde(MDA),and changed the activity of antioxidant enzymes.PBDE-209 inhibited the proliferation of Caco-2 cells and induced cytotoxicity.Changes in ROS generation and mitochondrial membrane potential(MMP)indicated that PBDE-209 caused oxidative stress in Caco-2 cells.Real-time quantitative PCR assay showed that PBDE-209 inhibited the m RNA expression of nuclear factor-E2-related factor 2(Nrf2)related to antioxidant defense.In addition,PBDE-209 increased the m RNA expression of FAS and cytochrome P4501A1(CYP1A1)in cells.These results suggested that PBDE-209 exert intestinal toxicity by inducing apoptosis and oxidative stress injury,and inhibiting antioxidant defense pathways.Additionally,we explored the effect of hesperidin intervention on reproductive toxicity induced by PBDE-209 in male mice.Male pubertal mice were exposed to PBDE-209(20,100,500 mg/kg·bw)and hesperidin(100 mg/kg·bw PBDE-209 + 100mg/kg·bw hesperidin)for 8 weeks.The sperm morphology,testis tissue damage,and the ultrastructure of seminiferous tubules were observed.We measured the organ coefficient,sex hormone levels,oxidative stress index,expressions of apoptosis-related proteins and m RNA in mice.The results showed that PBDE-209 increased the number of abnormal morphological spermatozoa in mice.The sex hormone levels were reduced,and the epididymal coefficient was increased in mice.We observed the injury of seminiferous tubules and a disordered arrangement of spermatogenic cells.PBDE-209 inhibited the proteins expression of blood-testis barrier-related and impaired blood-testis barrier integrity.PBDE-209 altered the expression of apoptosis-related proteins and m RNAs(Bax,Bcl-2,etc.)and induced apoptosis in testicular cells.PBDE-209 significantly increased MDA content and induced oxidative stress in mice testis.Compared with PBDE-209 groups,hesperidin reduced the number of abnormal spermatozoa in mice.The epididymis coefficient was decreased by hesperidin.Supplement of hesperidin alleviated the lesions of seminiferous tubules in mice testis.Also,hesperidin partially attenuated the damage of the blood-testis barrier and partially inhibited the apoptosis of testis cells in mice.This study showed that hesperidin intervention could alleviate PBDE-209-induced toxicity in pubertal mice to a certain extent.