Denervation caused by tullidora (Karwinskia humboldtiana)

Crude homogenate of the seed of the tullidora (Coyotillo, buckthorn; Karwinskia humboldtiana) fruit or a purified neurotoxin extracted from it was administered orally to male Wistar rats. Three to 5 weeks later, gait disturbances and progressive flaccid paralysis of the hindlimbs appeared in these animals which were then submitted to acute experiments. Single twitch and tetanic contractions of the soleus muscle were studied in the tullidora treated rats. The twitch tension elicited by direct stimulation of the muscle was greater than that produced by nerve stimulation. In addition, the tension of nerve-elicited twitches diminished as the stimulating electrode was moved towards the spinal cord, suggesting failure of nerve conduction. When the muscle was directly stimulated, contraction and relaxation were slower than normal and the tetanus/twitch tension ratio was subnormal. These data suggest partial denervation of the soleus muscle under the action of the toxin. Electron microscopy revealed abnormal motor-nerve endings with few synaptic vesicles and denervated end-plates. Degenerative changes of axons and myelin disturbances were frequently seen in the intramuscular branches of the soleus nerve. However, alterations of this type were less severe in the nerve sections closer to the spinal cord and no significant changes were detected at the upper portion of the sciatic nerve. It is concluded that the paralysis produced by the tullidora toxin is the result of both conduction block of the nerve impulses and muscle denervation.