Changes of mitochondrial ultrastructures and function in central nervous tissue of hens treated with tri-ortho-cresyl phosphate (TOCP)

• Published in: Human & experimental toxicology Vol. 30; no. 8; pp. 1062 - 1072
• Main Authors: Xing Xin, Tao Zeng, Dou, Dan-Dan, Sheng Zhao, Du, Jing-Yun, Pei, Jing-Jing, Xie, Ke-Qin, Zhao, Xiu-Lan
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.08.2011; Sage Publications; Sage Publications Ltd
• Subjects: Animals; Behavior, Animal - drug effects; Biological and medical sciences; Cerebral Cortex - drug effects; Cerebral Cortex - physiopathology; Cerebral Cortex - ultrastructure; Cerebrum; Chemical and industrial products toxicology. Toxic occupational diseases; Chickens; Cortex; Dose-Response Relationship, Drug; Electron microscopy; Esters; Medical sciences; Membrane permeability; Membrane potential; Membrane Potential, Mitochondrial - drug effects; Mitochondria; Mitochondria - drug effects; Mitochondria - ultrastructure; Mitochondrial Membrane Transport Proteins - metabolism; Mitochondrial Swelling - drug effects; Morphology; Neurotoxicity; Neurotoxicity Syndromes - etiology; Neurotoxicity Syndromes - pathology; Neurotoxicity Syndromes - physiopathology; Oil; Permeability; Phenobarbital; Phosphate; Plasticizers - toxicity; Poultry; Sodium; Solvents; Spinal cord; Spinal Cord - drug effects; Spinal Cord - physiopathology; Spinal Cord - ultrastructure; Succinate dehydrogenase; Time Factors; Toxicity; Toxicology; Tritolyl Phosphates - toxicity; Ultrastructure; Various organic compounds; Ventral horn; tri-ortho-cresyl phosphate (TOCP); morphological changes; mitochondrial permeability transition (MPT); organophosphorus ester-induced delayed neurotoxicity (OPIDN); methyl thiazolyl tetrazolium (MTT) reduction; Nervous system diseases; Neuropathy; Permeability; Hen; Vertebrata; Mitochondria; Neurotoxicity; Treatment; Ultrastructure; Animal; Delayed toxicity; Morphological change; Organophosphorus compounds; Nervous tissue; Aves
• ISSN: 0960-3271; 1477-0903
• DOI: 10.1177/0960327110386815

Tri-ortho-cresyl phosphate (TOCP), an organophosphorus ester, is capable of producing organophosphorus ester-induced delayed neurotoxicity (OPIDN) in humans and sensitive animals. The mechanism of OPIDN has not been fully understood. The present study has been designed to evaluate the role of mitochondrial dysfunctions in the development of OPIDN. Adult hens were treated with 750 mg/kg·bw TOCP by gavage and control hens were given an equivalent volume of corn oil. On day 1, 5, 15, 21 post-dosing, respectively, hens were anesthetized by intraperitoneal injection of sodium pentobarbital and perfused with 4% paraformaldehyde. The cerebral cortex cinerea and the ventral horn of lumbar spinal cord were dissected for electron microscopy. Another batch of hens were randomly divided into three experimental groups and control group. Hens in experimental groups were, respectively, given 185, 375, 750 mg/kg·bw TOCP orally and control group received solvent. After 1, 5, 15, 21 days of administration, they were sacrificed and the cerebrum and spinal cord dissected for the determination of the mitochondrial permeability transition (MPT), membrane potential (Δψ m) and the activity of succinate dehydrogenase. Structural changes of mitochondria were observed in hens’ nervous tissues, including vacuolation and fission, which increased with time post-dosing. MPT was increased in both the cerebrum and spinal cord, with the most noticeable increase in the spinal cord. Δψm was decreased in both the cerebrum and spinal cord, although there was no significant difference in the three treated groups and control group. The activity of mitochondrial succinate dehydrogenase assayed by methyl thiazolyl tetrazolium (MTT) reduction also confirmed mitochondrial dysfunctions following development of OPIDN. The results suggested mitochondrial dysfunction might partly account for the development of OPIDN induced by TOCP.