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Alterations in rat axonal cytoskeletal proteins induced by in vitro and in vivo 2,5-hexanedione exposure.

Authors
DeCaprio-AP; O'Neill-EA
Source
Toxicol Appl Pharmacol 1985 Apr; 78(2):235-247
NIOSHTIC No.
00147792
Abstract
The effects of 2,5-hexanedione (110134) on axonal cytoskeletal proteins were studied in rats. Male Wistar-rats were administered 8 weeks, or for 8 weeks plus a 9 week recovery period. The animals were observed for clinical symptoms and weighed at the end of the study. The animals were killed and assayed for histopathologic changes in the peripheral and central nervous systems. Serum and axonal cytoskeletal proteins from the central nervous system were isolated. Axonal cytoskeletal proteins were studied by polyacrylamide gel electrophoresis. Serum and axonal cytoskeletal proteins were assayed for pyrrole adduct formation. Experimental rats gained weight at slower rates than control animals. Rats treated for 5 or 8 weeks with 2,5-hexadione showed ataxia and hindlimb paralysis. Swollen and degenerating axons were observed in the peripheral and central nervous systems. Nine weeks of recovery reversed the peripheral nerve damage, but had no effect on central nervous system damage. Gel electrophoresis detected discrete new protein bands in brain stem and spinal cord axonal protein preparations, and high molecular weight nonmigrating proteinaceous material in all treated animals. The concentration of nonproteinaceous material increased with length of exposure. Nine weeks of recovery reversed these changes. A 2,5-dimethyl-pyrrole adduct was detected in serum and axonal cytoskeletal protein in all treated animals after 2 weeks. Nine weeks of recovery after the 8 week exposure resulted in the pyrrole adduct disappearing from serum proteins; however, residual amounts of the adduct were still present in axonal cytoskeletal proteins. The authors conclude that the mechanism of action of 2,5-hexanedione and other gamma diketones involves the formation of pyrrole in axonal proteins.
Keywords
NIOSH-Publication; NIOSH-Grant; Neurotoxic-effects; Cytology; Cytotoxins; Quantitative-analysis; Cytolysis; Cytotoxic-effects; Protein-chemistry; Proteins; Toxic-materials; Toxicology; Toxins; Toxic-effects
Contact
Biochem and Genetic Toxicology New York State Dept of Health Empire State Plaza Albany, N Y 12201
CODEN
TXAPA9
CAS No.
110-13-4
Publication Date
19850401
Document Type
Journal Article
Funding Amount
133853
Funding Type
Grant
Fiscal Year
1985
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-01972
Issue of Publication
2
ISSN
0041-008X
Priority Area
Neurotoxic Disorders; Neurotoxic-effects
Source Name
Toxicology and Applied Pharmacology
State
NY
Performing Organization
New York State Dept of Health, New York, New York
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