SAGE Journals Online
Advertisement
Sign In to gain access to subscriptions and/or personal tools.

 

Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Advertisement

Sign In to gain access to subscriptions and/or personal tools.
Human & Experimental Toxicology
This Article
Right arrow Full Text (PDF)
Right arrow References
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Bhattacharya, R
Right arrow Articles by Vijayaraghavan, R
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bhattacharya, R
Right arrow Articles by Vijayaraghavan, R
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Promising role of a-ketoglutarate in protecting against the lethal effects of cyanide

R Bhattacharya

Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior-474002, Madhya Pradesh, India; rbhattacharya41{at}rediffmail.com pharm_tox{at}yahoo.co.in

R Vijayaraghavan

Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior-474002, Madhya Pradesh, India

Treatment of cyanide poisoning generally includes amyl nitrite and//or sodium nitrite (SN) in combination with sodium thiosulphate (STS). However, in many instances of cyanide poisoning, use of nitrites is contraindicated due to their strong vasoactive properties. a-Ketoglutarate (a-KG) antagonizes cyanide poisoning by cyanohydrin formation. Protective efficacy of graded doses of a-KG (p.o.) as pretreatment, simultaneous treatment or post-treatment was evaluated against acute potassium cyanide (KCN) poisoning (p.o.) in female rats. Pretreatment with a-KG (0.125–2.0 g//kg) exhibited dose-and time-dependent effects and was found to be effective even when given up to 60 min prior to KCN. Addition of STS significantly enhanced the protective efficacy of a-KG at all the doses and time intervals. A 10-min pretreatment with a-KG increased the LD50 of KCN by 7-fold, which was further increased 28-fold by the addition of both SN and STS. Simultaneous treatment with a-KG (2.0 g//kg) increased the LD50 of KCN by 7-fold, which was doubled by the addition of STS. However, addition of SN did not confer any additional protection. Post-treatment with a KG+STS minimized the mortality by 50% but did not significantly extend the survival time in KCN (2 LD50)-administered rats. KCN (0.75 LD50) inhibited rat brain cytochrome oxidase, which was significantly protected by pretreatment or simultaneous treatment with a-KG and STS. Considering the efficacy and safety of peroral a-KG, a promising treatment regimen consisting of a-KG +STS or a-KG+SN+STS is proposed depending upon the situation.

Key Words: a-ketoglutarate • cyanide antidote • cyanide poisoning • cytochrome oxidase • protection • protection index

Human & Experimental Toxicology, Vol. 21, No. 6, 297-303 (2002)
DOI: 10.1191/0960327102ht255oa
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?




Advertisement