Lipid peroxidation and changes in cytochrome c oxidase and xanthine oxidase activity in organophosphorus anticholinesterase induced myopathy

Cultured hepatocytes and hemisphere neurons from chick embryos and mouse neuroblastoma cells were exposed to carbon tetrachloride (CC14; 0, 1, 2, 3 and 4mM) for 1 hour, using a perfusion system developed for studying the effects of volatile substances. In the perfused cultures, three parameters were compared: lipid peroxidation, membrane integrity and cellular respiration. In addition, cytochrome C oxidase activity was determined after incubation of cell homogenates with CC14. A concentration-dependent increase in lipid peroxidation and membrane permeability was found in the neuroblastoma cells. The hepatocytes responded to a lesser extent with respect to membrane permeability and their lipid peroxidation did not differ from that of controls. The hepatocytes responded with a 35% decrease in respiration when exposed to 3mM CC14, and a 20% decrease in cytochrome C oxidase activity after treatment with 1.5mM CCl4. In the neuronal cells, much smaller decreases in respiration were found and their cytochrome C oxidase activity remained unaffected. These results are very similar to those obtained after incubation in a closed chamber system. However, the perfused cells were found to be less sensitive to CCl4 than cells exposed under static conditions.

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Xanthine oxidase and activated neutrophils cause oxidative damage to skeletal muscle after contractile claudication

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00684.2003 ◽

2004 ◽

Vol 286 (1) ◽

pp. H252-H256 ◽

Cited By ~ 22

Author(s):

A. R. Judge ◽

S. L. Dodd

Keyword(s):

Skeletal Muscle ◽

Lipid Peroxidation ◽

Oxidative Damage ◽

Xanthine Oxidase ◽

Muscle Damage ◽

Protein Oxidation ◽

Oxidase Activity ◽

Neutrophil Infiltration ◽

Xanthine Oxidase Activity ◽

Infiltration Control

We previously showed oxidative damage and edema within skeletal muscle after contractile claudication. To investigate the sources of this oxidative damage in the gastrocnemius muscle, we administered allopurinol (Allo, to inhibit xanthine oxidase) and cyclophosphamide (Cyclo, to deplete neutrophils) before inducing contractile claudication in male Sprague Dawley rats. Contractile claudication (ligated stimulated, LS) caused a significant increase in xanthine oxidase activity [sham ligated stimulated (SS) = 2.57 ± 0.07; LS = 3.22 ± 0.07] and neutrophil infiltration (SS = 0.47 ± 0.03; LS = 0.91 ± 0.10) compared with controls (SS), and this was associated with increased lipid peroxidation, protein oxidation, muscle damage, and edema. Pretreatment with Allo attenuated the increase in xanthine oxidase activity and attenuated lipid hydroperoxides (control LS = 12.85 ± 0.50; Allo LS = 9.96 ± 0.71), muscle damage, and neutrophil infiltration (control LS = 0.91 ± 0.10; Allo LS = 0.61 ± 0.07). This latter finding suggests that xanthine oxidase-derived oxidants are chemotactic to neutrophils. Pretreatment with Cyclo reduced neutrophil infiltration (control LS = 0.91 ± 0.10; Cyclo LS = 0.55 ± 0.02) and attenuated lipid peroxidation (control LS = 12.85 ± 0.50; Cyclo LS = 6.462 ± 0.62), protein oxidation (control LS = 2.59 ± 0.47; Cyclo LS = 1.77 ± 0.60), muscle damage, and edema. Together, these data indicate that contractile claudication causes an increase in xanthine oxidase activity and neutrophils in muscle and that inhibition of these oxidant sources protects against oxidative stress, muscle damage, and edema.

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