X-Message-Number: 30184
Date: Thu, 20 Dec 2007 23:37:16 -0800 (PST)
Subject: Dithiothreitol: powerful protection against toxicity

[The mechanism of dithiothreitol protection against allyl alcohol
toxicity is apparently unknown. Could dithiothreitol help reduce
vitrification solution toxicity as well?]

Toxicology. 1994 Jan 26;86(1-2):147-61.
Dithiothreitol reversal of allyl alcohol cytotoxicity in isolated rat
  Rikans LE, Cai Y. Department of Pharmacology, College of Medicine,
University of Oklahoma Health Sciences Center, Oklahoma City 73190.
  Reversal by dithiothreitol (DTT) of allyl alcohol cytotoxicity was
investigated in isolated rat hepatocytes. Allyl alcohol-induced protein
sulfhydryl loss, bleb formation, and cell death were prevented by DTT,
when it was added to hepatocytes 30 min after the toxicant. The
protective effect of DTT also was demonstrated in cells that were washed
after 30 min of exposure to allyl alcohol, indicating that protection was
not related to inhibition of allyl alcohol metabolism or inactivation of
acrolein. DTT reversed the cell surface protrusions that formed during
exposure to allyl alcohol, but reversal of blebbing did not insure that
the cells would remain viable. Glutathione disulfide was not formed in
allyl alcohol-treated cells, and DTT reversal of cytotoxicity occurred
without restoring glutathione levels. Moreover, protection against allyl
alcohol toxicity required the continuous presence of DTT. The results
suggest that initial events in the toxic process are reversible, and that
DTT can prevent cytotoxicity if added to hepatocytes before irreversible
damage occurs; however, the mechanism by which DTT exerts its protection
is not clear.
PMID: 8134921

Arch Biochem Biophys. 1989 Dec;275(2):551-8.
Allyl alcohol- and acrolein-induced toxicity in isolated rat hepatocytes.
  Silva JM, O'Brien PJ. Faculty of Pharmacy, University of Toronto,
Ontario, Canada.
  Incubation of isolated hepatocytes with allyl alcohol results in GSH
depletion and subsequent cytotoxicity which is prevented by pyrazole, an
inhibitor of alcohol dehydrogenase. Both GSH depletion and cytotoxicity
were much more rapid when hepatocytes were incubated with acrolein, the
reactive metabolite, and were not affected by pyrazole. However,
cytotoxicity of both allyl alcohol and acrolein was enhanced by the
aldehyde dehydrogenase inhibitors cyanamide and
disulfiram. Malondialdehyde, a lipid peroxidation product, was also
formed when hepatocytes were incubated with either agent, and treatment of
the hepatocytes with a ferric ion chelator, desferrioxamine, or an
antioxidant delayed the cytotoxicity without affecting GSH
depletion. Although no GSSG was formed and addition of disulfide
reductant dithiothreitol did not restore GSH levels, cytotoxicity was
prevented if dithiothreitol was added some time after either agent.
PMID: 2596853

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