Résumé
Abstract only Tumor Necrosis Factor‐α (TNF‐α) is an inflammatory cytokine present at high levels in sepsis, cancer, and other severe chronic diseases. TNF‐α is thought to be a major regulator of muscle wasting associated with these diseases. In addition to muscle wasting, TNF‐α is known to induce contractile dysfunction in skeletal muscle independent of muscle cachexia. We have previously shown that a single intraperitoneal (i.p.) dose of TNF‐α increases intracellular oxidant generation and depresses maximal force in mouse diaphragm. Pretreatment of male ICR mice with antioxidants injected i.p. with either Trolox, Superoxide Dismutate, Catalase, L‐Name, or vehicle 1 hr before receiving TNF‐α 100ug/kg, lowers cytosolic oxidant activity (p<0.05) and partially inhibits contractile losses (p<0.05) in diaphragm. We hypothesized that loss in force caused by TNF‐α was due to alterations in the contractile apparatus via oxidative stress. To test this hypothesis we have adapted the skinned single fiber technique to mouse diaphragm. Permeabilized (Triton X100, 1%) single diaphragm muscle fibers from control and treated mice were isolated and attached to a force transducer and activated in pCa solutions (9.0 – 4.5 pCa). TNF‐α did not have a significant effect on maximal Ca2+‐activated force. On the other hand, there was a trend for a rightward shift in the force/pCa relationship in response to TNF‐α (p<0.08). Supported by NIH HL59878