Oxygen radicals in experimental shock: effects of spin-trapping nitrones in ameliorating shock pathophysiology (see comments)

Journal Article · Wed Apr 01 00:00:00 EST 1992 · Critical Care Medicine; (United States)

DOI:https://doi.org/10.1097/00003246-199204000-00012· OSTI ID:5308698

Novelli, G P ^[1]

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1. Institute of Anesthesiology and Intensive Care, University of Florence, Careggi Hospital, (Italy)

Circulatory shock is accepted as a consequence of an acute oxygen radical overgeneration. Spin-trapping nitrones inactivate free radicals by forming relatively stable adducts. Three spin-trapping nitrones (N-tert-phenyl-butyl-nitrone; alpha-4-pyridyl-oxide-N-tert-butyl-nitrone; 5-5,dimethyl,1,pyrroline-N-oxide) were tested regarding their role in the pathophysiology and evolution of circulatory shock in rats. A prospective, randomized, controlled trial of spin-trapping nitrones in rats experiencing three different models of circulatory shock was designed. In the first group, endotoxic, traumatic, and mesenteric artery occlusion shock (all 100% lethal in control experiments) was prevented by the ip administration of N-tert-phenyl-butyl-nitrone (150 mg/kg); alpha-4-pyridyl-oxide-N-tert-butyl-nitrone (100 mg/kg); or 5-5,dimethyl,1,pyrroline-N-oxide (100 mg/kg). However, the evolution of shock was unaffected by the same compounds when all three nitrones had been previously inactivated by exposure to light and air. In the second group, microcirculatory derangements that were provoked by endotoxin and were observed in the mesocecum of rats were completely prevented by pretreatment with either peritoneal administration of each of the three nitrones or by their topical application to the microscopic field. While the rats survived after systemic treatment, those rats receiving topical nitrones died from endotoxic shock. In the third group, cell-membrane stiffness (a sign of peroxidative damage) was measured by spin-probes and electron-spin resonance in mitochondrial and microsomal membranes. Cell membranes obtained from shocked rats were more rigid than those membranes of controls. However, the membranes obtained from rats that were submitted to trauma or endotoxin after pretreatment with N-tert-phenyl-butyl-nitrone had normal stiffness.

• OSTI ID: 5308698
• Journal Information: Critical Care Medicine; (United States), Vol. 20:4; ISSN 0090-3493
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
NITROGEN OXIDES
BIOLOGICAL EFFECTS
RADICALS
BIOSYNTHESIS
BIOLOGICAL SHOCK
CELL MEMBRANES
ELECTRON SPIN RESONANCE
LIPIDS
OXYGEN
RATS
ANIMALS
CELL CONSTITUENTS
CHALCOGENIDES
ELEMENTS
MAGNETIC RESONANCE
MAMMALS
MEMBRANES
NITROGEN COMPOUNDS
NONMETALS
ORGANIC COMPOUNDS
OXIDES
OXYGEN COMPOUNDS
PATHOLOGICAL CHANGES
RESONANCE
RODENTS
SYNTHESIS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology