Antioxidant and anti-apoptotic effects of tocotrienol-rich fraction against streptozotocin-induced diabetic retinopathy in rats

Biomed Pharmacother. 2022 Sep:153:113533. doi: 10.1016/j.biopha.2022.113533. Epub 2022 Aug 17.

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.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Apoptosis / drug effects
  • Diabetes Mellitus, Experimental* / metabolism
  • Diabetic Retinopathy* / chemically induced
  • Diabetic Retinopathy* / drug therapy
  • Oxidative Stress
  • Rats
  • Rats, Sprague-Dawley
  • Streptozocin* / metabolism
  • Streptozocin* / pharmacology
  • Superoxide Dismutase / metabolism
  • Tocotrienols* / pharmacology
  • Tocotrienols* / therapeutic use

Substances

  • Antioxidants
  • Tocotrienols
  • Streptozocin
  • Superoxide Dismutase