Acute toxicity of some synthetic cyanogens in rats and their response to oral treatment with alpha-ketoglutarate.
Oral toxicity of several cyanogens and their reversal by alpha-ketoglutarate (A-KG; oral) were studied in rats. LD(50) of acetonitrile (ATCN), acrylonitrile (ACN), malononitrile (MCN), propionitrile (PCN), sodium nitroprusside (SNP), and succinonitrile (SCN) was 4891, 143.3, 69.8, 122.9, 69.8 and 488.7 mg/kg, respectively while the protection index of A-KG (ratio of LD(50) of cyanogens in the presence or absence of A-KG) was>2.0 against MCN (7.6), PCN (2.7) and SNP (3.6) only. We further studied the efficacy of A-KG against acute toxicity of these three cyanogens (0.75 LD(50)) on various hematological and biochemical variables in blood and soft tissues 24h post-exposure. We observed increase in white blood cells (SNP), plasma alanine (PCN, SNP) and aspartate (PCN) aminotransferase, lactate dehydrogenase (MCN, PCN, SNP), Na(+) (MCN, PCN) and cyanide (PCN), and decrease in K(+) (MCN, SNP) accompanied by an increase in brain, kidney and liver malondialdehyde (PCN), decrease in brain glutathione peroxidase, glutathione reductase (PCN, SNP), reduced glutathione (MCN, PCN, SNP) and cytochrome oxidase (PCN), liver rhodanese (PCN, SNP), and kidney cytochrome oxidase (PCN). The study indicates that (i) PCN was most toxic among all the cyanogens and (ii) beside cyanide, A-KG could be considered as an effective antidote for cyanogens.
Bhattacharya
R
R
Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior, Madhya Pradesh, India. rbhattacharya41@rediffmail.com
Satpute
R M
RM
Hariharakrishnan
J
J
Tripathi
H
H
Saxena
P B
PB
D000284:Administration, Oral; D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D001774:Blood Chemical Analysis; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D003486:Cyanides / Q000097:blood; D005260:Female; D007656:Ketoglutaric Acids / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D009570:Nitriles / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism; D011041:Poisoning / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D013861:Thiocyanates / Q000097:blood; D023382:Toxicity Tests, Acute
D000931:Antidotes; D003486:Cyanides; D007656:Ketoglutaric Acids; D009570:Nitriles; D013861:Thiocyanates; D010088:Oxidoreductases; C031760:thiocyanate