X-Message-Number: 29970
Date: Sun, 21 Oct 2007 10:36:38 -0700 (PDT)
From: 
Subject: BHA as a pretreatment to cryonics

[Although cryoprotectant injury is the major roadblock to fully reversible
cryostasis, chilling injury is another factor. BHA is an example of a
ERK1/2 inhibitor which can inexpensively deal with the later problem. In
addition to being incorporated directly into cryoprotectant solutions,
pretreatment of the patient with BHA, while still conscious merits some
consideration.]

Transplantation. 2007 Apr 15;83(7):948-53.
Inhibition of ERK1/2 activation by phenolic antioxidants protects kidney
tubular cells during cold storage.
    Karhum ki P, Tiitinen SL, Turpeinen H, Parkkinen J. Finnish Red Cross
Blood Service, Helsinki, Finland.
    BACKGROUND: Cold storage of tissues induces reactive oxygen species
(ROS), which contribute to cell injury. We have compared different
antioxidants in protection of renal tubular cells against hypothermia
injury and studied their effect on cold-induced mitogen-activated protein
(MAP) kinase activation. METHODS: Cultured renal tubular epithelial cells
(LLC-PK1) were stored in University of Wisconsin solution supplemented
with compounds tested for 16 hr at 4 degrees C. Release of lactate
dehydrogenase and cellular adenosine triphosphate were
measured. Activation of MAP kinases was determined by Western
blotting. Intracellular ROS were monitored with a fluorescent
probe. RESULTS: Cold storage resulted in a substantial loss of cell
viability. The simple phenol butylated hydroxyanisol (BHA) most
effectively prevented hypothermia-induced cell injury, whereas about
100-fold higher concentration of the polyphenol epigallocatechin gallate
(EGCG) was needed, although EGCG most effectively scavenged intracellular
ROS elicited by serum withdrawal. The MEK inhibitor U0126 and reduced
nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor
diphenyleneiodonium effectively protected the cells against hypothermia
injury. ERK1/2 was rapidly activated during chilling of the cells and
this was inhibited by BHA but not by EGCG. CONCLUSION: The results
suggest that chilling of renal epithelial cells induces ROS generation by
NADPH oxidase, which leads to rapid activation of the MEK-ERK1/2 cascade
and initiation of cell injury. This can be prevented by antioxidants.
PMID: 17460567

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