Protection from cold injury by deferoxamine, an iron chelator.
The presence of hydroxyl radical (OH) has been implicated in the pathogenesis of cold injury. Since iron is known to catalyze the OH formation responsible for cellular injury, this study was designed to examine whether an iron chelator such as deferoxamine can salvage a tissue from cold injury. Cold injury was induced in the hind limbs of rabbits. The experimental group received 0.6 mM of deferoxamine through the femoral vein prior to cooling of the limbs. Deferoxamine reduced the tissue injury, as evidenced by the decreased release of lactate dehydrogenase, a nonspecific marker for cellular injury. In addition, this drug inhibited OH formation and lipid peroxidation when examined by monitoring the formation of conjugated dienes and malonaldehyde, presumptive markers for lipid peroxidation. Rewarming of the cooled limbs was also associated with the loss of membrane phospholipids, with the corresponding accumulation of lysophosphoglycerides and free fatty acids, especially linoleic and arachidonic acids. Deferoxamine prevented the loss of phospholipids and inhibited the accumulation of amphipathic lipid products. These results indicates that deferoxamine salvaged the tissue from cold injury, possibly by preventing the formation of OH presumably by chelating iron, thus protecting the phospholipids from free radical attack.
Maity
S
S
Department of Surgery, University of Connecticut School of Medicine, Farmington.
Lu
D
D
Russel
J C
JC
Lyengar
J
J
Das
D K
DK
D000818:Animals; D003080:Cold Temperature / Q000009:adverse effects*; D003676:Deferoxamine / Q000627:therapeutic use*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005609:Free Radicals; D006878:Hydroxides; D017665:Hydroxyl Radical; D007501:Iron / Q000502:physiology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008563:Membrane Lipids / Q000378:metabolism; D009132:Muscles / Q000293:injuries / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D011817:Rabbits
D005230:Fatty Acids, Nonesterified; D005609:Free Radicals; D006878:Hydroxides; D008563:Membrane Lipids; D010743:Phospholipids; D017665:Hydroxyl Radical; D007501:Iron; D007770:L-Lactate Dehydrogenase; D003676:Deferoxamine