Carbon Monoxide Releasing Molecule-3 Alleviates Oxidative Stress and Apoptosis in Selenite-Induced Cataract in Rats via Activating Nrf2/HO-1 Pathway

Abstract

Purpose

This study investigated the protective effect of carbon monoxide releasing molecule-3 (CORM-3), the classical donor of carbon monoxide, on selenite-induced cataract in rats and explore its possible mechanism.

Methods

Sprague-Dawley rat pups treated with sodium selenite (Na₂SeO₃) were chosen as the cataract model. Fifty rat pups were randomly divided into 5 groups: Control group, Na₂SeO₃ (3.46 mg/kg) group, low-dose CORM-3 (8 mg/kg/d) + Na₂SeO₃ group, high-dose CORM-3 (16 mg/kg/d) + Na₂SeO₃ group, and inactivated CORM-3 (iCORM-3) (8 mg/kg/d) + Na₂SeO₃ group. The protective effect of CORM-3 was tested by lens opacity scores, hematoxylin and eosin staining, TdT-mediated dUTP nick-end labeling assay, and enzyme-linked immunosorbent assay. Besides, quantitative real-time PCR and western blotting were used for mechanism validation.

Results

Na₂SeO₃ induced nuclear cataract rapidly and stably, and the achievement ratio of Na₂SeO₃ group was 100%. CORM-3 alleviated lens opacity of selenite-induced cataract and attenuated the morphological changes of the rat lens. The levels of antioxidant enzymes GSH and SOD in rat lens were also increased by CORM-3 treatment. CORM-3 significantly reduced the ratio of apoptotic lens epithelial cells, besides, CORM-3 decreased the expression of Cleaved Caspase-3 and Bax induced by selenite and increased the expression of Bcl-2 in rat lens inhibited by selenite. Moreover, Nrf-2 and HO-1 were upregulated and Keap1 was downregulated after CORM-3 treatment. While iCORM-3 did not exert the same effect as CORM-3.

Conclusions

Exogenous CO released from CORM-3 alleviates oxidative stress and apoptosis in selenite-induced rat cataract via activating Nrf2/HO-1 pathway. CORM-3 may serve as a promising preventive and therapeutic strategy for cataract.

Keywords:

• CORM-3
• selenite-induced cataract
• oxidative stress
• apoptosis
• Nrf2
• HO-1

Author contributions

Jinglan Li was responsible for methodology, investigation, resources, writing original draft, and data curation. Zi Ye and Zhaohui Li were responsible for the supervision, project administration, funding acquisition, writing review, and editing. Yang Huang was responsible for language editing. Yating Liu, Tianju Ma, Lixiong Gao, and Yu Luo carried out the investigation and resources.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All data generated and analyzed in the present study are available from the corresponding author upon reasonable request.

Additional information

Funding

This study was supported by the National Natural Science Foundation of China [81670838; 82070937; 81870640] and the National Natural Science Foundation for Young Scientists of China [82101097].