Degenerative changes in skeletal muscle of hens with tri- ortho-cresyl phosphate-induced delayed neurotoxicity: Altered acetylcholinesterase molecular forms and increased plasma creatine phosphokinase activity

Abstract

Degenerative changes in skeletal muscle were studied in hens with a delayed neuropathy induced with TOCP (tri- ortho-cresyl phosphate) that was characterized by axonal fragmentation in the sciatic nerve and by paralysis of the legs. Mean muscle weight and fiber diameter were significantly decreased in the musculus gastrocnemius, a leg muscle innervated by a branch of the sciatic nerve. The muscle fibers also exhibited abnormal morphology and high extrajunctional AChE activity in the muscle fiber sarcoplasm. Biochemical studies showed that the conentrations of acetylcholinesterase (AChE, EC 3.1.1.7) and nonspecific cholinesterase (EC 3.1.1.8) activities were doubled in the gastrocnemius of hens with delayed neurotoxicity compared to control. Sedimentation of the AChE molecular forms on sucrose density gradients showed that the relative activity of the 7 S form more than doubled and that of the 20 S form was decreased by 57% compared to normal hens. Following the onset of delayed neurotoxicity, creatine phosphokinase (EC 2.7.3.2) activity in the plasma was four times normal, and it was decreased by 56% in the gastronemius. These changes were not observed in birds treated with parathion ( O,O-diethyl- p-nitrophenyl phosphorothioate), which suggested that the alterations were associated with the delayed neuropathy. Muscle atrophy occurred in the m. pectoralis major of birds treated with TOCP and parathion, but this finding may have been a secondary effect of both organophosphates.