Fluorinated Oxazolidine Derivative RS-10 Ameliorates Hyperglycemic Conditions and Restores Visual Function in an In
Sanjay Gopi1, S Prethiba1, M Chandhru1
1Toxicology and Pharmacology Laboratory, Department of Biotechnology, Faculty of Science and Humanities, SRM Institute of Science and Technology, Kattankulathur, India.
Purpose:
The pathogenesis of diabetic retinopathy involves oxidative stress, inflammation, and neuronal dysfunction, with oxidative stress playing a critical role in retinal cell injury. The current study evaluates the therapeutic potential of 3-(4-fluorophenyl)-4-(4-nitrophenyl)-1,2-oxazolidine, a fluorinated oxazolidine derivative with potent anti-inflammatory, antioxidant, and antidiabetic properties, in mitigating diabetic retinopathy-induced retinal damage using a zebrafish model.
Methods:
Adult zebrafish were divided into five groups: control (group I, no intervention), STZ-induced diabetic retinopathy (group II, 50 μL of 7 mg/mL STZ administered intraperitoneally followed by 1% glucose exposure for 30 min, with an intravitreal injection of 20 μL of 7% STZ on day 7), 3-(4-fluorophenyl)-4-(4-nitrophenyl)-1,2-oxazolidine low dose (group III, 50 μM 3-(4-fluorophenyl)-4-(4-nitrophenyl)-1,2-oxazolidine administered intraperitoneally on days 14 and 21 post-induction), 3-(4-fluorophenyl)-4-(4-nitrophenyl)-1,2-oxazolidine mid dose (group IV, 100 μM 3-(4-fluorophenyl)-4-(4-nitrophenyl)-1,2-oxazolidine administered intraperitoneally on days 14 and 21 post-induction), and 3-(4-fluorophenyl)-4-(4-nitrophenyl)-1,2-oxazolidine high dose (group V, 200 μM 3-(4-fluorophenyl)-4-(4-nitrophenyl)-1,2-oxazolidine administered intraperitoneally on days 14 and 21 post-induction). Retinal histomorphometry, optomotor response, oxidative stress markers, and inflammatory markers were assessed across all groups.
Results:
3-(4-Fluorophenyl)-4-(4-nitrophenyl)-1,2-oxazolidine treatment at 200 μM concentration significantly reduced ROS accumulation, lipid peroxidation, and restored antioxidant enzyme levels, indicating its potent antioxidant activity. Histopathological analysis revealed a marked reduction in retinal neuronal degeneration, preserved retinal structure, and enhanced neuronal integrity. Behavioral analysis showed improved visual function, with 3-(4-fluorophenyl)-4-(4-nitrophenyl)-1,2-oxazolidine-treated zebrafish displaying improved optokinetic and optomotor response with improved swimming behavior, suggesting functional preservation of retinal activity. Furthermore, molecular analysis revealed the modulation of key oxidative stress markers and pro-inflammatory cytokines such as tnf-α, il-1β with the suppression underscoring 3-(4-fluorophenyl)-4-(4-nitrophenyl)-1,2-oxazolidine's ability to mitigate inflammation and oxidative damage.
Conclusion:
These findings highlight the therapeutic efficacy of 3-(4-fluorophenyl)-4-(4-nitrophenyl)-1,2-oxazolidine in preventing diabetic retinopathy-related retinal degeneration by reducing oxidative stress and preserving retinal function, suggesting further investigation into its clinical applicability for managing retinal diseases linked to oxidative stress and inflammation.
