Acute toxicity of methyl isocyanate in rabbit: in vitro and in vivo effects on rabbit erythrocyte membrane.
Methyl isocyanate (MIC) interaction with the rabbit erythrocyte membrane increased the fluidity of the membrane and decreased the osmotic fragility of erythrocytes both in vitro and in vivo in rabbits intoxicated with MIC subcutaneously. MIC inhibited both acetylcholinesterase (AChE) and adenosine triphosphatase (ATPase) activities of erythrocytes dose-dependently in vitro, while in vivo a decreased trend in ATPase activity with unaltered AChE activity was observed. MIC also caused significant decrease in plasma sodium level with corresponding increase in potassium level in rabbits. The observed effects are due to MIC, per se, as the hydrolysis products of MIC, methylamine and N,N'-dimethylurea did not affect the erythrocyte fluidity and enzymes activities both in vitro and in vivo while they increased the osmotic fragility of erythrocytes in vivo in rabbits administered subcutaneously in equimolar concentration to MIC dosage. Inhibition of Na(+)-K(+)-dependent ATPase with altered permeability to cations and also probably water transport of plasma membrane due to MIC interaction are envisaged.
Jeevaratnam
K
K
Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior, India.
Vaidyanathan
C S
CS
D000110:Acetylcholinesterase / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D000986:Antisickling Agents / Q000633:toxicity*; D003485:Cyanates / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000201:enzymology; D005260:Female; D007279:Injections, Subcutaneous; D017953:Isocyanates; D009996:Osmotic Fragility / Q000187:drug effects; D011188:Potassium / Q000097:blood; D011817:Rabbits; D012964:Sodium / Q000097:blood
D000986:Antisickling Agents; D003485:Cyanates; D017953:Isocyanates; D012964:Sodium; C008461:methyl isocyanate; D000110:Acetylcholinesterase; D000251:Adenosine Triphosphatases; D011188:Potassium