Effect of cerivastatin on peripheral capillary permeability to albumin and peripheral nerve function in diabetic rats.

OBJECTIVE: To examine the effect of cerivastatin on capillary permeability to albumin and peripheral nerve function in diabetic rats. ANIMALS: Diabetes was induced in male Wistar rats by i.p. injection of streptozotocin (STZ) at the age of 5 days. Forty diabetic rats were randomized in two groups: one treated by cerivastatin (diabetic treated group, DT) and the other untreated (diabetic untreated group, DU). The data were compared to a group of normal rats. MEASUREMENTS: The peripheral capillary filtration of albumin (CFA) was studied on a limb by a non-invasive isotopic method, and nerve electrophysiological measurements were performed. Rats were followed-up until 6 months. In group DU albumin retention (AR) increased by 3 months and lymphatic uptake of interstitial albumin was impaired at 6 months. None of these disorders was observed in group DT. Motor and sensory nerve conduction velocities (MNCV and SNCV) were significantly slower at 6 months in group DU but not in group DT as compared to control rats. The duration of the sensory nerve action potential (SNAP) was significantly longer in group DU than in control rats at 6 months whereas it did not differ in group DT and in control animals. CONCLUSIONS: This study shows that cerivastatin may prevent the peripheral increase in CFA and lymphatic dysfunction induced by diabetes. These beneficial effects on microcirculation may be involved in the prevention of nerve function deterioration. The underlying mechanisms are likely to be independent of a lipid-lowering effect, but their clarification needs further investigations.

Nerve electrophysiological changes in rats with early induced diabetes.

In rats with diabetes induced at weaning, pathological examinations have shown that the reduction of myelin thickness occurs earlier than axon size reduction. The aim of this study was to provide a detailed description of neurophysiological changes during nerve growth and maturation in rats with streptozotocin-induced diabetes in prepubertal stage. Five-day male Wistar rats received an injection of streptozotocin. Motor and sensory conduction velocities increased until 6.5 months in diabetic and control rats and at this age it became lower in diabetic rats. In diabetic rats, the amplitudes of the compound motor action potentials (CMAP) were lower by the 3 months and did not increase later. The amplitudes and areas of sensory action potentials (SNAP) increased until 9 months in both groups. SNAP duration decreased with ageing. Sensory peak 1 and peak 2 latencies became longer from 6.5 to 9 months in diabetic rats, with a longer latency difference between the 2 sensory peaks by 4 months. At 3 and 4 months of age, peak 1 and peak 2 latencies correlated with SNAP amplitude and duration in control rats but not in diabetic rats. In conclusion, in rats with early induced diabetes, the earliest electrophysiological impairments consist of lower CMAP amplitudes, and longer difference between latencies of sensory peaks 1 and 2. These sequential neurophysiological changes should be considered when testing new therapeutic approaches in diabetic neuropathy.