Effect of PEG-superoxide dismutase on the diaphragmatic response to endotoxin.
Although it is known that endotoxin can induce diaphragmatic dysfunction, the mechanism of this effect is not fully understood. However, because the effects of endotoxin on other tissues appear to be mediated in part by free radicals, the present study sought to determine if free radicals may also contribute to the diaphragmatic dysfunction induced by endotoxin administration. Studies were performed on four groups of hamsters. One group of animals received intraperitoneal injections of endotoxin on the first and second days of study (i.e., 10 and 20 mg/kg, respectively). The second group received saline rather than endotoxin, the third group received both endotoxin and a free radical scavenger, PEG-SOD (2,000 U/kg given intraperitoneally every 12 h on Days 1 and 2), and the fourth group received PEG-SOD alone. All groups were killed on the third study day (i.e., 48 h after the initial injections). Diaphragmatic contractile function was assessed in vitro using muscle strips excised from the costal diaphragms of freshly killed animals; diaphragm samples were also assayed for malondialdehyde (MDA), a commonly used index of free-radical-mediated lipid peroxidation. MDA levels were higher in diaphragms from endotoxin-treated animals than from saline-treated control animals, and the contractility of diaphragm strips from endotoxin-treated animals was reduced when compared with strips from saline-treated control animals. Administration of PEG-SOD prevented MDA formation and contractile dysfunction in endotoxin-treated animals. Diaphragm contractility and MDA levels for animals given PEG-SOD alone were similar to those for saline-treated control animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Shindoh
C
C
Pulmonary Division, Case Western Reserve University, Cleveland, Ohio 44109.
Dimarco
A
A
Nethery
D
D
Supinski
G
G
D000818:Animals; D006224:Cricetinae; D003964:Diaphragm / Q000187:drug effects* / Q000503:physiopathology; D004731:Endotoxins / Q000494:pharmacology*; D016166:Free Radical Scavengers; D005609:Free Radicals; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D008647:Mesocricetus; D009119:Muscle Contraction / Q000502:physiology; D011092:Polyethylene Glycols; D013482:Superoxide Dismutase
D004731:Endotoxins; D016166:Free Radical Scavengers; D005609:Free Radicals; D011092:Polyethylene Glycols; D008315:Malondialdehyde; D013482:Superoxide Dismutase; C063471:polyethylene glycol-superoxide dismutase