Department of Pharmacology, Faculty of Medicine, Manipal University College Malaysia (MUCM), Bukit Baru, 75150 Melaka, Malaysia; Centre for Neuroscience Research (NeuRon), Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, 47000 Sungai Buloh, Selangor, Malaysia.
Centre for Neuroscience Research (NeuRon), Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, 47000 Sungai Buloh, Selangor, Malaysia.
Biomed Pharmacother. 2022 Sep;153:113533. doi: 10.1016/j.biopha.2022.113533. Epub 2022 Aug 17.
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.
氧化应激是糖尿病视网膜病变 (DR) 的关键因素，与视网膜细胞凋亡有关。本研究探讨了生育三烯酚（TRF），一种有效的抗氧化剂，对链脲佐菌素 (STZ) 诱导的 DR 大鼠的视觉行为、视网膜形态、细胞凋亡和氧化还原状态的影响。Sprague-Dawley 大鼠分为 3 组：非糖尿病 (N)，腹腔内注射柠檬酸盐缓冲液；糖尿病用载体 (DV) 治疗；糖尿病用 TRF (DT) 治疗，腹腔内注射 STZ (55mg/kg) 诱导糖尿病。DT 口服 100mg/kg TRF 治疗 12 周，而 DV 和 N 给予载体。在 12 周时，在开放场域中评估一般和视觉行为反应。然后处死大鼠，处理视网膜进行苏木精和伊红 (H&E) 和末端转移酶介导的 dUTP 缺口末端标记 (TUNEL) 染色。测量视网膜抗氧化剂、脂质过氧化和抗凋亡标志物。DT 的一般和视觉行为反应与 N 相似。与 N 相比，DV 和 DT 的视网膜厚度和细胞计数较低。与 DV 相比，DT 中观察到的 TUNEL 阳性细胞数量较少 (1.48 倍，p<0.001)，这与视网膜 caspase-3 表达相关 (2.31 倍，p<0.001)。DT 的视网膜氧化应激低于 DV，表现为还原型谷胱甘肽升高 (2.10 倍，p<0.05)、超氧化物歧化酶升高 (1.12 倍，p<0.05) 和过氧化氢酶升高 (1.40 倍，p<0.001)，以及丙二醛降低 (2.54 倍，p<0.001)。总之，口服 TRF (100mg/kg) 补充 12 周可降低 STZ 诱导的 DR 大鼠的视网膜氧化应激，从而减少视网膜细胞凋亡并保护视网膜形态。这些发现与视觉行为反应的保留有关。
