title: Effect of sub-acute oral cyanide administration in rats: protective efficacy of alpha-ketoglutarate and sodium thiosulfate.
abstract: Chronic toxicity of cyanide in humans and animals has been previously described. Alpha-ketoglutarate (alpha-KG) and sodium thiosulfate (STS) are known to confer remarkable protection against acute cyanide poisoning in rodents. Their efficacy against sub-acute or chronic cyanide exposure is not known. The objective of the present study was to assess the sub-acute toxicity of potassium cyanide (KCN) in female rats following oral administration of 7.0 mg/kg (0.5 LD50) for 14 d. The effect of alpha-KG (oral; 1.0 g/kg) and/or STS (intraperitoneal, 1.0 g/kg) on cyanide toxicity was also evaluated. Various hematological and biochemical indices were determined after 7 d of treatment and additional parameters like organ-body weight index (OBI) and histology of brain, heart, lung, liver, kidney and spleen were performed after 14 and 21 d (recovery group) of cyanide exposure. Sub-acute exposure of KCN did not produce any significant change in body weight of the animals, OBI, hematology and the levels of blood urea, creatinine, aspartate aminotransferase, triiodothyronine (T3) and tetraiodothyronine (T4). The levels of temporal glutathione disulfide (GSSG) and hepatic malondialdehyde (MDA), reduced glutathione (GSH) and GSSG were unaffected. However, in KCN treated animals elevated levels of blood glucose and reduced levels of alanine aminotransferase were observed. Activities of cytochrome c oxidase in the brain and rhodanese in the liver were diminished. Reduced levels of GSH and enhanced levels of MDA in brain were observed. Increased levels of blood thiocyanate were observed in all the treatments of KCN. Additionally, KCN also produced various histological changes in the brain, heart, liver and kidney. Although, treatment of alpha-KG and STS alone significantly blunted the toxicity of KCN, concomitant use of both interventions afforded to maximum protection. This study indicates a promising role of alpha-KG and STS for the treatment of prolonged cyanide exposures.
authors.affiliation: Division of Pharmacology and Toxicology, Defense Research and Development Establishment, Jhansi Road, Gwalior 474 002 (MP), India.
authors.forename: R K
authors.initials: RK
authors.lastname: Tulsawani
authors.forename: M
authors.initials: M
authors.lastname: Debnath
authors.forename: S C
authors.initials: SC
authors.lastname: Pant
authors.forename: Om
authors.initials: O
authors.lastname: Kumar
authors.forename: A O
authors.initials: AO
authors.lastname: Prakash
authors.forename: R
authors.initials: R
authors.lastname: Vijayaraghavan
authors.forename: R
authors.initials: R
authors.lastname: Bhattacharya
mesh_terms: D000284:Administration, Oral; D000410:Alanine Transaminase / Q000032:analysis / Q000378:metabolism; D000825:Animal Structures / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D003486:Cyanides / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000633:toxicity*; D003576:Electron Transport Complex IV / Q000032:analysis / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000097:blood; D019803:Glutathione Disulfide / Q000097:blood; D007656:Ketoglutaric Acids / Q000494:pharmacology* / Q000627:therapeutic use; D008315:Malondialdehyde / Q000032:analysis / Q000378:metabolism; D011041:Poisoning / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D013861:Thiocyanates / Q000097:blood; D013884:Thiosulfate Sulfurtransferase / Q000032:analysis / Q000378:metabolism; D013885:Thiosulfates / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors; D014284:Triiodothyronine / Q000097:blood; D014508:Urea / Q000097:blood
chemical_list: D001786:Blood Glucose; D003486:Cyanides; D007656:Ketoglutaric Acids; D013861:Thiocyanates; D013885:Thiosulfates; D014284:Triiodothyronine; D008315:Malondialdehyde; D014508:Urea; D003404:Creatinine; D003576:Electron Transport Complex IV; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D013884:Thiosulfate Sulfurtransferase; D005978:Glutathione; C017717:sodium thiosulfate; C031760:thiocyanate; D019803:Glutathione Disulfide