Treatment with Actovegin^® Improves Sensory Nerve Function and Pathology in Streptozotocin-Diabetic Rats via Mechanisms Involving Inhibition of PARP Activation

Abstract

Background:

Diabetic neuropathy is one of the most severe complications of diabetes, affecting approximately one-third of diabetic patients. We investigated the potential neuroprotective effect of Actovegin^®, a deproteinized hemoderivative of calf blood, in an animal model of diabetic neuropathy.

Methods:

A single intravenous injection of streptozotocin (STZ, 55 mg/kg) was used to induce experimental diabetes in male Sprague-Dawley rats. Actovegin^® (200 or 600 mg/kg) was administered intraperitoneally from day 11 to day 40 post-STZ exposure. N-acetylcysteine (NAC) was used as a positive control and was added to drinking water (0.2 g/l) from day 2 until day 40. Measurements to assess efficacy included sensory nerve conduction velocity (SNCV), intraepidermal nerve fiber density (IENFD), and poly(ADP-ribose) content.

Results:

A decrease (35%) in sensory nerve conduction velocity (SNCV) was seen in STZ-induced diabetic rats from day 10 post-STZ administration and persisted at days 25 and 39. At study completion (day 41), a decrease (32%) in intraepidermal nerve fiber density (IENFD) was found in hind-paw skin biopsies from STZ-rats. Reduced SNCV and IENFD were significantly ameliorated by both doses of Actovegin^®. More­over, 600 mg/kg Actovegin^® markedly decreased poly(ADP-ribose) polymerase (PARP) activity in sciatic nerves from STZ-diabetic rats as assessed by poly(ADP-ribose) content.

Conclusion:

Actovegin^® improved several para­meters of experimental diabetic neuropathy via mechanisms involving suppression of PARP activation, providing a rationale for treatment of this disease in humans.

Key words

Actovegin^® - streptozotocin - diabetes - neuropathy - neuroprotection - PARP

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