title: Biochemical, oxidative and histological changes caused by sub-acute oral exposure of some synthetic cyanogens in rats: ameliorative effect of α-ketoglutarate.
abstract: Time-dependent cyanide generation and acute toxicity of six different cyanogens were reported earlier, out of which malononitrile (MCN), propionitrile (PCN), and sodium nitroprusside (SNP) were found to be very toxic. We report here 14 d sub-acute toxicity of MCN, PCN, and SNP (oral; 1/10 LD50 daily) in female rats, and its amelioration by α-ketoglutarate (α-KG; oral; 5.26 mmol/kg; +5 min), a potential cyanide antidote. Significant decrease in white blood cells (PCN, SNP), platelets count (PCN), and blood glucose levels (MCN, PCN, SNP) was accompanied by elevated levels of alanine aminotransferase, lactate dehydrogenase (MCN, PCN, SNP), and aspartate aminotransferase (PCN, SNP). Oxidative damage was evidenced by diminished total antioxidant status in plasma and enhanced malondialdehyde levels in liver and kidney. This was accompanied by diminished levels of reduced glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase in the brain, liver and kidney. We also observed increased levels of blood cyanide and thiocyanate, together with inhibition of cytochrome c oxidase and thiosulfate-sulfur transferase activities in total brain and liver homogenate, respectively. Cyanogens also produced several histological changes in all the organs studied. Post-treatment with α-KG significantly abrogated the toxicity of cyanogens, indicating its utility as an antidote for long-term cyanogen exposure.
authors.affiliation: Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474 002, MP, India. Electronic address: rbhattacharya41@rediffmail.com.
authors.forename: Rahul
authors.initials: R
authors.lastname: Bhattacharya
authors.affiliation: Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474 002, MP, India.
authors.forename: Pooja
authors.initials: P
authors.lastname: Rao
authors.affiliation: Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474 002, MP, India.
authors.forename: Poonam
authors.initials: P
authors.lastname: Singh
authors.affiliation: Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474 002, MP, India.
authors.forename: Shiv Kumar
authors.initials: SK
authors.lastname: Yadav
authors.affiliation: Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474 002, MP, India.
authors.forename: Preeti
authors.initials: P
authors.lastname: Upadhyay
authors.affiliation: Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474 002, MP, India.
authors.forename: Sandhya
authors.initials: S
authors.lastname: Malla
authors.affiliation: Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474 002, MP, India.
authors.forename: Niranjan Laxman
authors.initials: NL
authors.lastname: Gujar
authors.affiliation: Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474 002, MP, India.
authors.forename: Vinay
authors.initials: V
authors.lastname: Lomash
authors.affiliation: Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474 002, MP, India.
authors.forename: Satish Chandra
authors.initials: SC
authors.lastname: Pant
mesh_terms: D000284:Administration, Oral; D000818:Animals; D005260:Female; D007656:Ketoglutaric Acids / Q000494:pharmacology*; D009570:Nitriles / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007656:Ketoglutaric Acids; D009570:Nitriles; C011206:cyanogen
keywords: Cyanogens; Oxidative damage; Protection; Sub-acute toxicity; α-Ketoglutarate