Effects of sulforaphane on the ferroptosis pathway and iron homeostasis in rats with diabetic retinopathy
10.13389/j.cnki.rao.2025.0150
- VernacularTitle:萝卜硫素对糖尿病视网膜病变大鼠铁死亡途径和铁稳态的影响
- Author:
Fa LIU
1
;
Dan HAN
;
Ziwei XU
;
Kunying LU
;
Weiqi ZHANG
Author Information
1. 150036 黑龙江省哈尔滨市,哈尔滨二四二医院眼三科
- Publication Type:Journal Article
- Keywords:
sulforaphane;
diabetic retinopathy;
ferroptosis;
iron homeostasis;
oxidative stress
- From:
Recent Advances in Ophthalmology
2025;45(11):870-876,882
- CountryChina
- Language:Chinese
-
Abstract:
Objective To reveal the effects of sulforaphane(SFN)on the ferroptosis pathway and iron homeostasis in rats with diabetic retinopathy(DR).Methods A DR rat model was established by a single intraperitoneal injection of streptozotocin at 65 mg·kg-1.After modeling,the rats were randomly divided into six groups(n=12 per group):Group C(control group),DR group,0.5SFN group,1.0SFN group,2.0SFN group,and 2.0SFN+Erastin group.Group C con-sisted of non-intervention control rats,while the other groups were DR model rats.Groups C and DR were orally adminis-tered 0.5 g·L-1 sodium carboxymethyl cellulose(CMC-Na).The 0.5SFN,1.0SFN,and 2.0SFN groups were orally ad-ministered SFN at 0.5,1.0,and 2.0 mg·kg-1,respectively.The 2.0SFN+Erastin group was orally administered 2.0 mg·kg-1 SFN and simultaneously received a tail intravenous injection of the ferroptosis inducer Erastin at 10.0 mg·kg-1.The intervention lasted for 4 weeks.Fasting blood glucose(FPG)was measured with a glucometer,glycosylated hemoglo-bin(GHb)was detected by visible spectrophotometry,and fasting insulin(FINS)was measured by ELISA.Retinal tissues were subjected to hematoxylin-eosin(HE)staining and periodic acid-Schiff(PAS)staining.The level of reactive oxygen species(ROS)in the retina was detected using the DCFH-DA probe,malondialdehyde(MDA)was measured by the TBA method,and reduced glutathione(GSH)was assessed by spectrophotometry.Retinal Fe2+content was determined by spectrophotometry.The mRNA expression levels of ferritin heavy chain 1(FTH1),ferroportin 1(FPN1),transferrin re-ceptor(TFRC),glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),thioredoxin 1(Trx1),and thioredoxin-interacting protein(TXNIP)in the retina were detected by qRT-PCR.GPX4 protein expression in the retina was detected by Western blot.Results Compared with the DR group,the 0.5SFN,1.0SFN,and 2.0SFN groups showed decreased FPG and GHb,increased FINS,improved retinal morphology with reduced neovascular capillaries,decreased levels of ROS and MDA,increased GSH levels,decreased retinal Fe2+content,increased FTH1 and FPN1 mRNA levels,de-creased TFRC mRNA levels,increased retinal GPX4,SLC7A11,and Trx1 mRNA levels,decreased TXNIP mRNA levels,and increased retinal GPX4 protein levels(all P＜0.05).Compared with the 2.0SFN group,the 2.0SFN+Erastin group showed increased FPG and GHb,decreased FINS,aggravated retinal damage with increased neovascular capillaries,elevat-ed levels of ROS and MDA,decreased GSH levels,increased retinal Fe2+content,decreased FTH1 and FPN1 mRNA levels,increased TFRC mRNA levels,decreased retinal GPX4,SLC7A11,and Trx1 mRNA levels,increased TXNIP mRNA levels,and decreased retinal GPX4 protein levels(all P＜0.05).Conclusion SFN alleviates DR in rats by inhibiting the ferrop-tosis pathway and maintaining iron homeostasis.
