Antibodies to neural proteins in organophosphorus-induced delayed neuropathy (OPIDN) and its amelioration.
The development of OPIDN and the efficacy of experimental intervention using the calcium-channel blocker verapamil were used as a model to test the serial time-measurements of serum autoantibodies against neuronal cytoskeletal proteins [e.g., neurofilament triplet (NF)] and glial proteins [myelin-basic protein (MBP) and glial fibrillary-acidic protein (GFAP)] as biomarkers of neurotoxicity and its amelioration. Ten White Leghorn hens (>7 months, 1.2-1.8 kg) were administered phenyl-saligenin phosphate (PSP; 2.5 mg/kg; im), a dose reported to induce a 70% decrease in neurotoxic esterase (NTE) activity. Five of the hens were administered verapamil (7 mg/kg; im) for 4 days starting one day before PSP administration. Serum was isolated from blood collected by serial brachial venepuncture before PSP (day 0) administration and on days 3, 7 and 21 after PSP administration, each hen acting as its own control. Serum antibodies (IgG) to NF-L, NF-M, NF-H, MBP, and GFAP were assayed using an ELISA. There were no detectable levels of antibodies on days 0 and 3. IgG against all neural proteins were detected on days 7 and 21, with titer levels being significantly (p< or =0.05) higher in sera of hens receiving PSP only. Anti-NF-L titers were highest compared to those against NF-M, NF-H or MBP at 21 days. Titers of anti-NF-L and anti-MBP significantly (p< or =0.01) correlated with clinical scores at days 7 and 21. Detection of anti-NF and anti-MBP antibodies confirms the neuroaxonal degeneration accompanied by myelin loss reported in this model of OPIDN and the amelioration of neuropathy using verapamil. The detection of anti-GFAP antibodies suggests CNS involvement in OPIDN, since astrocytes are only found therein. This study demonstrates that detection of neuroantibodies can be used as biomarkers of neuropathy development and to monitor the amelioration resulting from therapeutic intervention. Together with biomarkers of exposure neuroantibodies can be used to monitor neuropathogenesis due to environmental or occupational exposures.
El-Fawal
Hassan A N
HA
Neurotoxicology Laboratory, Division of Health Professions and Natural Sciences, Mercy College, Dobbs Ferry, NY 10522, USA. helfawal@mercy.edu
McCain
Wilfred C
WC
D000818:Animals; D000906:Antibodies / Q000032:analysis*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001323:Autoantibodies / Q000032:analysis / Q000096:biosynthesis; D001592:Benzyl Alcohols / Q000633:toxicity; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002645:Chickens; D004797:Enzyme-Linked Immunosorbent Assay; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis; D008297:Male; D004676:Myelin Basic Protein / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000276:immunology*; D020258:Neurotoxicity Syndromes / Q000276:immunology* / Q000378:metabolism*; D009943:Organophosphorus Compounds / Q000633:toxicity*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000276:immunology* / Q000473:pathology; D014317:Tritolyl Phosphates / Q000633:toxicity; D014700:Verapamil / Q000494:pharmacology
D000906:Antibodies; D001323:Autoantibodies; D001592:Benzyl Alcohols; D002121:Calcium Channel Blockers; D007074:Immunoglobulin G; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D009943:Organophosphorus Compounds; D014317:Tritolyl Phosphates; D014700:Verapamil; C010631:salicyl alcohol; C025541:tri-o-cresyl phosphate