Experimental ethambutol neuropathy in rats: Morphometric and teased-fiber studies

Abstract

Eight rats were given 500 mg/kg body weight of the antituberculous drug ethambutol orally every day for 3 months (group A), and 7 took 150 mg/kg of the drug for 9 months (group B). The sciatic nerves at midthigh level and the posterior tibial nerves at ankle level were studied with morphometric examination and teased-fiber method. The number of myelinated fibers/mm 2 of fascicular area was significantly reduced in both sciatic and posterior tibial nerves of group B. The pattern of frequency distribution of myelinated nerve fiber diameters of both groups was not different from that of the controls. Teased-fiber study revealed that many fibers were undergoing axonal degeneration in both groups A and B. In addition, regenerating fibers after axonal degeneration were observed in group B. These results showed that the predominant pathologic change in ethambutol neuropathy was axonal degeneration and that regeneration was already occurring in the animals taking a small dose of the drug for a long period. The fact that the degree of pathologic change was rather more severe in the sciatic nerve than in the posterior tibial nerve indicated that this was not a “dying-back” neuropathy.