ABSTRACT

Time of drug administration affects both the kinetics and dynamics of medications. This study investigated diurnal efficacy of alpha-lipoic acid (ALA), nifedipine, and glimepiride combination in the treatment of diabetic retinopathy. The study design comprised seven groups of rats, with groups 1 and 2 serving as non-diabetic and diabetic controls, respectively, receiving 1 ml/kg distilled water. All other groups were diabetic, and received 10 mg/kg glimepiride at 20:00 h. Groups 4–7 also received 20 mg/kg nifedipine at 08:00 h. In addition, groups 5–7 received 100 mg/kg ALA at 08:00 h, 14:00 h, and 20:00 h, respectively. Oral drug administration was for 28 days during which fasting and random blood glucose sampling were done weekly at 07:30 h and 13:30 h, respectively. On the 29^th day, rats were euthanized; blood was collected via the jugular veins for determination of serum ocular markers like magnesium, cholesterol, and triglyceride. Furthermore, the eyes were excised and their relative organ/body weight ratios determined. The right eyes were persevered in phosphate buffer for homogenization and determination of retina antioxidant profile (MDA, SOD, CAT, GSH), while the left eyes were preserved in formalin for histological examination. Results showed that treatment with ALA and glimepiride at 20:00 h along with nifedipine at 08:00 h resulted in better prognosis than other treatment groups and with improved glycemic control. Also, all their serum markers for retinopathy, organ weight, and histology did not differ significantly from that of the non-diabetic rats. Findings imply that diurnal efficacy in alpha-lipoic acid, nifedipine and glimepiride combination ameliorates diabetic retinopathy in rats and may be beneficial in the treatment of diabetic retinopathy.

摘要

给药时间会影响药物的动力学和动力学。本研究调查了 α-硫辛酸 (ALA)、硝苯地平和格列美脲联合治疗糖尿病视网膜病变的昼夜疗效。研究设计包括七组大鼠，第 1 组和第 2 组分别作为非糖尿病和糖尿病对照，接受 1 ml/kg 蒸馏水。所有其他组均为糖尿病患者，并在 20:00 h 接受 10 mg/kg 格列美脲。第 4-7 组还在 08:00 时接受了 20 mg/kg 硝苯地平。此外，第 5-7 组分别在 08:00、14:00 和 20:00 接受 100 mg/kg ALA。口服给药持续 28 天，在此期间分别在每周 07:30 和 13:30 进行空腹和随机血糖采样。29^日一天，老鼠被安乐死；通过颈静脉收集血液，用于测定血清眼部标志物，如镁、胆固醇和甘油三酯。此外，切除眼睛并确定它们的相对器官/体重比。右眼保存在磷酸盐缓冲液中用于匀浆和测定视网膜抗氧化谱（MDA、SOD、CAT、GSH），而左眼保存在福尔马林中用于组织学检查。结果表明，在 20:00 时使用 ALA 和格列美脲以及在 08:00 时使用硝苯地平进行治疗，预后优于其他治疗组，并且血糖控制得到改善。此外，他们的视网膜病变、器官重量和组织学的所有血清标志物与非糖尿病大鼠的血清标志物没有显着差异。研究结果表明，α-硫辛酸的昼夜功效，