Activity and gene expression profile of certain antioxidant enzymes in different organs of rats after subacute cyanide exposure: effect of alpha-ketoglutarate.
Oxidative stress plays a crucial role in mediating cyanide toxicity. The present study addresses the effect of cyanide on activity and gene-expression profile of certain antioxidant enzymes and the expression of heat shock protein (HSP-70) in different organs of rats. Rats were treated with 0.50 LD(50) (7.0 mg/kg) of potassium cyanide (KCN; oral) and/or alpha-ketoglutarate (A-KG; 1.0 g/kg; oral) daily for 14 days, and various biochemical variables were measured in brain, liver, and kidney after 7 and 14 days of treatments and a 7-day recovery period. Cyanide significantly reduced the activity of glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), and catalase (CA) in all the organs after 7 days, while the activity of GPx in brain, liver, and kidney, GR in liver, and CA in brain remained diminished up to 14 days. The gene-expression profile of corresponding enzymes did not show any difference between the control and treatment groups. Elevated levels of malondialdehyde were observed in brain and kidney 7 and 14 days after cyanide. Cyanide also increased the expression of HSP-70 activity in brain after 7 days alone. Regression of toxicity was observed after the withdrawal of KCN. Treatment of A-KG was found to prevent all the biochemical alterations caused by cyanide. This study reveals that oxidative stress caused by cyanide was independent of the expression of antioxidant enzyme activity at the gene level, and all changes responded favorably to A-KG, indicating its therapeutic potential.
Hariharakrishnan
Janardhanan
J
Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior, India.
Anand
Tamatam
T
Satpute
Ravindra M
RM
Jayaraj
Ravindran
R
Prasad
G B K S
GB
Bhattacharya
Rahul
R
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000633:toxicity*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism; D007656:Ketoglutaric Acids / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010088:Oxidoreductases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011190:Potassium Cyanide / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D028761:Withholding Treatment
D004791:Enzyme Inhibitors; D018840:HSP70 Heat-Shock Proteins; D007656:Ketoglutaric Acids; D008315:Malondialdehyde; D010088:Oxidoreductases; D005978:Glutathione; D011190:Potassium Cyanide