Antioxidant and anti-apoptotic effects of tocotrienol-rich fraction against streptozotocin-induced diabetic retinopathy in rats
- PMID: 36076612
- DOI: 10.1016/j.biopha.2022.113533
Antioxidant and anti-apoptotic effects of tocotrienol-rich fraction against streptozotocin-induced diabetic retinopathy in rats
Abstract
Oxidative stress, a key player in diabetic retinopathy (DR), is associated with retinal cell apoptosis. This study investigated the effect of tocotrienol-rich fraction (TRF), a potent antioxidant, towards visual behaviour, retinal morphology, cells apoptosis and redox status in streptozotocin (STZ)-induced DR rats. Sprague-Dawley rats were divided into 3 groups: non-diabetic (N), was injected with citrate buffer intraperitoneally, diabetic treated with vehicle (DV), and diabetic treated with TRF (DT), were injected with STZ intraperitoneally (55 mg/kg) to induce diabetes. DT received 100 mg of TRF/kg orally for 12-weeks, whereas DV and N received vehicle. The general and visual-behaviour responses were assessed at week 12 in an open field arena. Rats were then sacrificed, and retinae were processed for haematoxylin and eosin (H&E) and terminal transferase-mediated dUTP nick end-labelling (TUNEL) staining. Retinal antioxidant, lipid peroxidation and anti-apoptotic markers were measured. The general and visual-behaviour responses in DT were comparable to N. Retinal thickness and cell counts were lower in DV and DT compared to N. Lower number of TUNEL-positive cells were observed in DT compared to DV (1.48-fold, p < 0.001) which correlated with retinal caspase-3 expression (2.31-fold, p < 0.001). The retinal oxidative stress in DT was lower than DV as indicated by higher reduced glutathione (2.10-fold, p < 0.05), superoxide dismutase (1.12-fold, p < 0.05) and catalase (1.40-fold, p < 0.001), and lower malondialdehyde (2.54-fold, p < 0.001). In conclusion, oral TRF (100 mg/kg) supplementation for 12-weeks reduces retinal oxidative stress in STZ-induced DR rats, which in turn reduces retinal cell apoptosis and protects retinal morphology. These findings were associated with preservation of the visual-behaviour responses.
Keywords: Diabetic retinopathy; Neurodegeneration; Oxidative stress; Tocotrienol-rich fraction; Visual behaviour.
Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.
Conflict of interest statement
Conflict of interest statement The authors report no conflicts of interest. All authors have contributed substantially to the conception, design, drafting of the article, and in final approval of the version of the manuscript to be submitted. All authors have jointly decided to designate Dr Nurul Alimah Abdul Nasir to be responsible for decision-making regarding the presence of authors and the order of their presence in the manuscript. Dr Nurul Alimah Abdul Nasir has also been selected by all authors to be responsible for all future communication with the journal regarding this manuscript.
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