Chronopharmacology of the alpha-lipoic acid/nifedipine/glimepiride combination in the amelioration of retinopathy in rats

Abstract

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 29th 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.