Preservation of motor nerve function during early degeneration by the 21-aminosteroid anti-oxidant U74006F

The effects of 5 days of pretreatment with the 21-aminosteroid anti-oxidant U74006F have been examined on the rate of functional degeneration of cat soleus motor nerve terminals after axon section. Female cats were dosed for 5 days with either 7.7, 13.0 or 30.0 mg/kg (average doses) of U74006F p.o. twice daily followed by unilateral sciatic nerve section at the hip level on day 5. On day 7, the bilateral in vivo soleus nerve muscle prep. was set up to assess the neuromuscular functional status of the 48 h degenerating soleus nerve terminals in comparison to the contralateral non-sectioned preparation. In untreated cats, the ratio of the nerve-evoked (0.4 Hz) contractile tension of the 48 h nerve-sectioned to that of the contralateral non-sectioned was only 52 ± 8%. U74006F pretreatment produced a dose-related improvement with the 13.0 mg/kg dose having the best effect; the ratio was 86 ± 5% (P < 0.01 vs untreated). The maintenance of tetanic tension during a 10 s period of 100 Hz nerve stimulation was also improved by the 13.0 mg/kg dose from only 54.0 ± 5.2% in untreated animals to 72.2 ± 5.7 (P < 0.02). These results show a preservation of motor nerve function during early degeneration by the anti-oxidant U74006F thus providing further evidence for a free radical-mediated process in anterograde degeneration.