Pyridoxal 5'-phosphate as an antidote for cyanide, spermine, gentamicin, and dopamine toxicity: an in vivo rat study.
Pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, readily forms complexes with a wide variety of potentially toxic substances, including cyanide (KCN), spermine (SPM), gentamicin (GM), and dopamine (DOP). The role of PLP as an antidote for these toxicants in vivo was studied. Rats were given intraperitoneal injections of the toxicant, followed by injections of either saline or PLP. For KCN, PLP increased the LD50 from 0.088 to 0.188 mmol/kg and extended the survival time at the highest dose employed from a median of 3 min to a median of 60 min. For SPM, PLP increased the LD50 from 0.162 to 0.262 mmol/kg and prevented death from renal failure at all doses employed except the highest. PLP protected against GM-induced neuromuscular paralysis and death. In the case of DOP, results were equivocal, but no deaths were seen in the PLP-treated rats. The combination of individually nontoxic doses of GM, DOP, and SPM caused death with renal tubular necrosis, pulmonary edema and hemorrhages, congestion of the viscera, and a diffuse coagulopathy. Because many seriously ill patients have elevated SPM levels and are given GM and/or DOP, we suggest that further investigation of the potential protective role of PLP in serious illness be undertaken.
D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D003486:Cyanides / Q000633:toxicity*; D004298:Dopamine / Q000633:toxicity*; D005260:Female; D005839:Gentamicins / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects; D008168:Lung / Q000187:drug effects; D011190:Potassium Cyanide / Q000633:toxicity*; D011732:Pyridoxal Phosphate / Q000494:pharmacology*; D011736:Pyridoxine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013096:Spermine / Q000633:toxicity*
D000931:Antidotes; D003486:Cyanides; D005839:Gentamicins; D013096:Spermine; D011732:Pyridoxal Phosphate; D011736:Pyridoxine; D011190:Potassium Cyanide; D004298:Dopamine