Abstract
Time-dependent effects of alpha-lipoic acid/nifedipine/glimepiride combination on diabetic neuropathies were investigated in rats. 7 groups (n=9) of rats were used. First and second groups were apparently normal and diabetic rats respectively, and were administered 1mL/kg distilled water. The rest of the groups were diabetic and administered 10mg/kg glimepiride at night-time (8:00 pm). Groups 4-7 were administered additional 20mg/kg nifedipine at morning-time (8:00 am), while groups 5-7 were also administered 100mg/kg alpha-lipoic acid (ALA) in the morning, afternoon and night-time respectively (8:00 am, 2:00 pm and 8:00 pm). During the 28 days of oral treatment, paw pressure, tail immersion and motor coordination tests were conducted. The rats were euthanized on the 29th day after a charcoal meal. The small intestines were excised to determine intestinal transit while the brain was collected, homogenised and used to determine levels of oxidative stress. Data show that treatment with ALA at 8:00 am or 2:00 pm significantly (P≤0.01) produced a delay in the onset and improved prognosis of neuropathies. Treatment with ALA at 8:00 pm prevented manifestation of neuropathies throughout the study with positive antioxidant effects. Time-dependent ALA treatment in combination with nifedipine and glimepiride should be studied in humans with an approximately similar circadian timing. This may provide additional clinical therapeutic options for diabetic neuropathies.
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