In Vitro Screen for Cyanide Antidotes
Abstract
We previously reported that isolated rat pheochromocytoma (PC 12) cells may be useful for in vitro evaluation of potential cyanide antidotes. The present study shows further results and in vivo validation of this in vitro approach. Ability to block a series of 6 biochemical markers of cyanide toxicity in PC12 cells (dopamine release, peroxide generation, cytosolic-free calcium) and inhibition of certain enzymes (catalase, superoxide dismutase and cytochrome oxidase) was evaluated for 39 different compounds from various pharmacological classes. Based on the composite scoring in all 6 assays, carbamazepine, mannitol, allopurinol and phenytoin were ranked as the most effective anticyanide compounds. In an attempt to maximize in vitro protection, combinations of potential antidotes were used. However, combinations were less effective than antidotes used alone in vitro assays. In some cases potential antidotes appear to interfere with each others actions in the in vitro screen. Known cyanide antidotes (e.g., pyruvate, mercaptopyruvate, alpha-ketoglutarate, naloxone and flunarizine) obtained relatively high ranking in the PC12 cell screen. Furthermore a significant correlation was found between protective effects (based on LD50s) of cyanide antidotes in mice and ranking in the in vitro screen.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 13, 1993
- Accession Number
- ADP008845
Entities
People
- Anumantha G Kanthasamy
- G. E. Isom
- J. L. Borowitz
- P. Mitchell
Organizations
- Purdue University