Cross-linking effect injury

Lipid peroxidation is one of the major sources of free-radical mediated injury that directly damages membranes and generates a number of secondary products. In particular, markers of lipid peroxidation have been found to be elevated in brain tissues and body fluids in several neurodegenerative diseases, and the role of lipid peroxidation has been extensively discussed in the context of their pathogenesis. Peroxidation of membrane lipids can have numerous effects, including increased membrane rigidity, decreased activity of membrane-bound enzymes (e.g., sodium pumps), altered activity of membrane receptors, and altered permeability [Anzai et al., 1999 Yehuda et al., 2002], In addition to effects on phospholipids, lipid-initiated radicals can also directly attack membrane proteins and induce lipid-lipid, lipid-protein, and protein-protein cross-linking, all of which obviously have effects on membrane function. 

Cole, D.J. Schell, R.M. Drummond, J.C. Reynolds, L. Focal cerebral ischemia in rats effect of hypervolemic hemodilution with diaspirin cross-linked hemoglobin versus albumin on brain injury and edema. Anesthesiology 1993, 78, 335-342. 

Cole, D.J. Drummond, J.C. Patel, P.M. Nary, J.C. Applegate, R.L., II. Effect of oncotic pressure of diaspirin cross-linked hemoglobin (DCLHb ) on brain injury after temporary focal cerebral ischemia in rats. Anesth. Analg. 1996, 83, 342-347. 

Piper, I.R. Garrioch, M.A. Souter, M.J. Andrews, P.J.D. Thomson, D. Effects of diaspirin cross-linked haemoglobin on past-traumatic cerebral perfusion pressure and blood flow in a rodent model of diffuse brain injury. Brit. J. Anaesthes. 1998, 80, 639-643. 

Although the exact mechanism by which mustard produces tissue injury is not known, the mechanism of action has been suggested to be its ability to directly alkylate DNA. This DNA alkylation and cross-linking in rapidly dividing cells such as basal keratinocytes, mucosal epithelium, and bone marrow precursor cells leads to cellular death and inflammatory reactions. Systemic effects with extensive exposures include bone marrow inhibition, with a drop in the white blood cell count, and gastrointestinal tract damage. 

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