Effect of acute tri-o-tolyl phosphate exposure on 2', 3'-cyclic nucleotide 3'-phosphohydrolase activity in hen neural...

The activity of 2', 3'-cyclic nucleotide 3'-phosphohydrolase (CNP, EC 3.1.4.37), a myelin-associated enzyme, was monitored in brain, spinal cord, and sciatic nerve homogenates from tri-o-tolyl phosphate (TOTP) and tri-m-tolyl phosphate (TMTP) treated hens. Atropinized adult White Leghorn hens were orally dosed with TOTP (200 mg/kg) or with TMTP (200 mg/kg). The treated birds were monitored daily for development of delayed neurotoxicity, and CNP activity was measured via spectrophotometry at the time of maximal locomotor impairment (27-35 days post dosing). The TOTP-treated birds manifested locomotor deficit by 15 days postdosing and exhibited T2-T4 ataxia at maximal locomotor impairment. The hens administered TMTP exhibited no signs of delayed neurotoxicity. CNP activity of sciatic nerve preparations from TOTP-dosed hens was significantly inhibited (p less than 0.05) at the time of maximal locomotor impairment. There was also a significant correlation between decreased CNP activity and the degree of ataxia at the time of maximal locomotor impairment. This decrease in sciatic nerve CNP activity was most likely associated with nerve fiber degeneration. The level of CNP activity in spinal cord and brain homogenates from TOTP-dosed birds was not markedly altered. TMTP-treated birds exhibited no change in neural tissue CNP activity. The results suggest that the criterion of decreased CNP activity may serve as a useful biochemical adjunct to established clinical, biochemical, and morphological methods in the assessment of chemically-induced neuropathies.