Antioxidant vitamin therapy alters sepsis-related apoptotic myocardial activity and inflammatory responses.
This study examined the effects of antioxidant vitamins on several aspects of sepsis-related myocardial signaling cascades. Sprague-Dawley rats were divided into four groups: group 1, vehicle-treated shams; group 2, sham-operated rats given antioxidant vitamins (vitamin C, 24 mg/kg; vitamin E, 20 U/kg; vitamin A, 417 U/kg; and zinc, 3.7 ng/kg) by oral gavage in 0.5 ml water twice daily for 3 days and no septic challenge (vitamin-treated, sham-operated rats); group 3, intratracheal delivery of Streptococcus pneumoniae, 4 x 10(6) colony forming units in a volume of 0.3 ml phosphate buffer solution; group 4, S. pneumonia challenge as described for group 3 plus antioxidant vitamins (as described for group 2). Hearts collected 24 h after septic challenge were used to examine several aspects of cell signaling and ventricular function. As a result, when compared with sham-operated rats, sepsis in the absence of antioxidant therapy promoted NF-kappaB activation, increased mitochondrial cytochrome c release, increased myocyte cytokine secretion, increased caspase activation, and impaired left ventricular function. Antioxidant vitamin therapy plus septic challenge prevented NF-kappaB activation, reduced mitochondrial cytochrome c release, decreased caspase activity, abrogated cardiomyocyte secretion of inflammatory cytokines, and improved myocardial contractile function. In conclusion, antioxidant vitamin therapy abrogated myocardial inflammatory cytokine signaling and attenuated sepsis-related contractile dysfunction, suggesting that antioxidant vitamin therapy may be a potential approach to treat injury and disease states characterized by myocardial dysfunction.
Carlson
Deborah
D
Dept. of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9160, USA.
Maass
David L
DL
White
D Jean
DJ
Tan
Jing
J
Horton
Jureta W
JW
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D017209:Apoptosis / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D009202:Cardiomyopathies / Q000188:drug therapy / Q000378:metabolism* / Q000382:microbiology; D020169:Caspases / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D011008:Pneumococcal Infections / Q000150:complications / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism*; D015398:Signal Transduction; D012964:Sodium / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000472:pathogenicity; D016277:Ventricular Function, Left; D014815:Vitamins / Q000627:therapeutic use*
D000975:Antioxidants; D016207:Cytokines; D016328:NF-kappa B; D014815:Vitamins; D045304:Cytochromes c; D012964:Sodium; D020169:Caspases; D002118:Calcium