3H-1,2-Dithiole-3-Thione Protects Lens Epithelial Cells against Fructose-Induced Epithelial-Mesenchymal Transition via Activation of AMPK to Eliminate AKR1B1-Induced Oxidative Stress in Diabetes Mellitus

Tsung-Tien Wu; Ying-Ying Chen; Chiu-Yi Ho; Tung-Chen Yeh; Gwo-Ching Sun; Ching-Jiunn Tseng; Pei-Wen Cheng

doi:10.3390/antiox10071086

3H-1,2-Dithiole-3-Thione Protects Lens Epithelial Cells against Fructose-Induced Epithelial-Mesenchymal Transition via Activation of AMPK to Eliminate AKR1B1-Induced Oxidative Stress in Diabetes Mellitus

Antioxidants (Basel). 2021 Jul 6;10(7):1086. doi: 10.3390/antiox10071086.

Authors

Tsung-Tien Wu^{1

2

3}, Ying-Ying Chen^{1

2}, Chiu-Yi Ho^{4

5}, Tung-Chen Yeh⁶, Gwo-Ching Sun⁷, Ching-Jiunn Tseng^{4

5}, Pei-Wen Cheng^{4

5}

Affiliations

¹ Department of Ophthalmology, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan.
² School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
³ Department of Optometry, Shu-Zen Junior College of Medicine and Management, Kaohsiung 81362, Taiwan.
⁴ Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan.
⁵ Department of Biomedical Science, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan.
⁶ Department of Internal Medicine, Division of Cardiology, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan.
⁷ Department of Anesthesiology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.

Abstract

Studies demonstrated that the receptor of advanced glycation end products (RAGE) induced epithelial-mesenchymal transition (EMT) formation in the lens epithelial cells (LECs) of diabetic cataracts. This work investigated how 3H-1,2-dithiole-3-thione (D3T) reduces EMT formation in LECs of the fructose-induced diabetes mellitus (DM). LECs were isolated during cataract surgery from patients without DM or with DM. In a rat model, fructose (10% fructose, eight weeks) with or without D3T (10 mg/kg/day) treatment induced DM, as verified by blood pressure and serum parameter measurements. We observed that the formation of advanced glycation end products (AGEs) was significantly higher in epithelial human lens of DM (+) compared to DM (-) cataracts. Aldose reductase (AKR1B1), AcSOD2, and 3-NT were significantly enhanced in the rat lens epithelial sections of fructose-induced DM, however, the phosphorylation level of AMPK^T172 showed a reversed result. Interestingly, administration of D3T reverses the fructose-induced effects in LECs. These results indicated that AMPK^T172 may be required for reduced superoxide generation and the pathogenesis of diabetic cataract. Administration of D3T reverses the fructose-induced EMT formation the LECs of fructose-induced DM. These novel findings suggest that the D3T may be a candidate for the pharmacological prevention of cataracts in patients with DM.

Keywords: 3H-1,2-dithiole-3-thione (D3T); AKR1B1; AMPK; diabetic cataracts; epithelial-mesenchymal transition (EMT).