A goldfish model for evaluation of the neurotoxicity of omega-conotoxin GVI A and screening of monoclonal antibodies.
The neurotoxicity of omega-conotoxin (omega-CgTx), a potent neuronal voltage-sensitive calcium channel blocker, was measured using a new bioassay. omega-CgTx was administered intraperitoneally (ip) to goldfish weighing approximately 1.6 g, and dose-related changes were observed over a 2-hr period. omega-CgTx induced time- and dose-dependent abnormal swimming behavior (ASB) and mortality. The antitoxin activity of the antibodies was investigated in vivo by either (1) preincubation of the antibody with omega-CgTx at 4 degrees C overnight, or (2) pretreatment with antibody, 30 min before omega-CgTx injection in a 10:1 antibody/omega-CgTx molar ratio. The LD50 dose of omega-CgTx in goldfish was 5 nmol/kg ip, and preincubation of monoclonal antibody (50 nmol/kg ip) with omega-CgTx (5 nmol/kg ip) significantly (p less than 0.05) reduced mortality, ASB, and toxicity time. The antitoxin activity of the monoclonal antibodies evidenced in the goldfish bioassay was further tested in the conscious rat. In the rat, the increases in mean arterial pressure and heart rate induced by omega-CgTx (0.03 nmol/rat icv) were significantly (p less than 0.02 and p less than 0.01, respectively) attenuated by preincubation of the toxin with the antibody (0.3 nmol/rat). We conclude that the goldfish bioassay provides a simple, accurate, and inexpensive in vivo model for the study of the toxicity of omega-CgTx.
Adeyemo
O M
OM
Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
Shapira
S
S
Tombaccini
D
D
Pollard
H B
HB
Feuerstein
G
G
Sirén
A L
AL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015220:Calcium Channels / Q000187:drug effects; D006054:Goldfish; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects*; D010456:Peptides, Cyclic / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D020866:omega-Conotoxin GVIA
D000911:Antibodies, Monoclonal; D015220:Calcium Channels; D010456:Peptides, Cyclic; D020866:omega-Conotoxin GVIA