The superoxide dismutase (SOD)-mimic manganese-deferoxamine (Mn-DFO) improves survival following hemorrhagic and endotoxic shock

Conference · Mon Feb 26 04:00:00 EST 1990 · FASEB Journal (Federation of American Societies for Experimental Biology); (United States)

OSTI ID:6054271

de Garavilla, L; Chermak, T; Valentine, H L; Hanson, R C ^[1]

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1. NOVA Pharmaceutical Corp., Baltimore, MD (United States)

The novel, low-molecular weight, organo-metallic complex Mn-DFO functions in vitro as an SOD-mimic effectively dismutating the superoxide radical. Oxygen-derived free radicals appear to be involved in the pathology of both endotoxic (ENDO) and hemorrhagic (HEM) shock whereby treatment with SOD is associated with improvements in survival. Therefore, the following models were utilized to evaluate the in vivo activity of Mn-DFO. Male rats (350-450g) were anesthetized with ketamine (100mg/kg, ip) and subjected to HEM hypotension by withdrawing approximately 40% of the animals' blood volume over a 10 minute period. MABP was maintained constant at 40mmHg for 60 minutes, followed by complete autoreinfusion. Survival was reduced to 20% in the control group at 24 hour post-reinfusion. A single post-shock dose of Mn-DFO (10mg/kg, iv) more than doubled the survival rate for up to 24 hour post-reinfusion as compared to control. Female mice (CFmal and-1, 20-25g) were challenged with 500ug of ENDO and 0.8ug of actinomycin/animal and dosed 1 hour pre and post with Mn-DFO (30mg/kg/dose, iv). Survival improved from 60% in the control group to 100% in the Mn-DFO group at 18 hours post ENDO challenge. Using a multiple dosing regimen, Mn-DFO significantly improved survival for up to 48 hours post-ENDO. Thus, unlike other SOD-mimics, Mn-DFO appears to exhibit in vivo activity.

• OSTI ID: 6054271
• Report Number(s): CONF-9104107--
• Conference Information: Journal Name: FASEB Journal (Federation of American Societies for Experimental Biology); (United States) Journal Volume: 4:3
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINES
ANIMALS
ANTIOXIDANTS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL SHOCK
CHELATING AGENTS
COMPLEXES
DEFEROXAMINE
ENZYMES
HEMORRHAGE
IN VIVO
KINETICS
MAMMALS
MANGANESE COMPLEXES
ORGANIC COMPOUNDS
OXIDOREDUCTASES
PATHOLOGICAL CHANGES
PROTEINS
RADICALS
RATS
REACTION KINETICS
RODENTS
SUPEROXIDE DISMUTASE
SUPEROXIDE RADICALS
SURVIVAL CURVES
SYMPTOMS
THERAPY
TRANSITION ELEMENT COMPLEXES
VERTEBRATES