Skip Navigation


ToxSci Advance Access originally published online on May 28, 2003
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
74/2/345    most recent
kfg135v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (2)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Valentovic, M. A.
Right arrow Articles by Minigh, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Valentovic, M. A.
Right arrow Articles by Minigh, J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Toxicological Sciences 74, 345-351 (2003)
Copyright © 2003 by the Society of Toxicology

IN VITRO TOXICOLOGY AND ALTERNATIVE TESTING

Pyruvate Attenuates Myoglobin in Vitro Toxicity

Monica A. Valentovic1 and Jennifer Minigh

Department of Pharmacology, Marshall University School of Medicine, 1542 Spring Valley Drive, Huntington, West Virginia 25704-9388

Myoglobinuria is a complication of crush injury as well as substance abuse. This study examined whether pyruvate modified myoglobin in vitro renal toxicity. Renal slices from Fischer-344 rats were incubated for 120 min with 0–12 mg/ml myoglobn. In an initial study, gluconeogenesis was stimulated by the addition of 10 mM pyruvate during the final 30 min. In all other studies, renal slices were incubated with myoglobin in the presence of 0 or 10 mM pyruvate for 120 min. Myoglobin increased lactate dehydrogenase (LDH) release and this was not modified by the presence of pyruvate for the last 30 min of the incubation. Myoglobin toxicity was reduced by coincubation of myoglobin with pyruvate for 120 min. LDH leakage was increased 1.2-, 1.7-, and 1.8-fold above control by 4, 10, and 12 mg/ml myoglobin, compared to 1.2, 1.3, and 1.3 fold in slices coincubated with 10 mM pyruvate, respectively. Myoglobin diminished adenosine triphophate (ATP) levels but pyruvate maintained a 5x higher level of ATP within the slices. Glucose (10 mM) provided protection only for the low concentration (4 mg/ml) of myoglobin. Myoglobin induced oxidative stress while pyruvate prevented the rise in lipid peroxidation and glutathione disulfides by myoglobin. Myoglobin diminished total glutathione levels in pyruvate-treated tissue, but glutathione levels remained higher than tissues incubated in the absence of pyruvate. These results indicate that pyruvate reduced toxicity by preventing oxidative stress and via a supply of an energy substrate.

Key Words: myoglobinuria; substance abuse; rhabdomyolysis; renal dysfunction; pyruvate; lactate dehydrogenase; glutathione levels.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.