Skin nitric oxide and its metabolites are increased in nonburned skin after thermal injuries.
Local and systemic inflammation can lead to progression of burn wounds, converting second- to third-degree wounds or extending the burn to adjacent areas. Previous studies have suggested that the skin is an important site of production of nitric oxide (NO), synthesized by inducible nitric oxide synthase (iNOS) activation after injury. NO increases in burned wounds, but its formation in noninjured skin has not been investigated. We hypothesized that after severe burns, NO and cytotoxic peroxynitrite would increase in noninjured skin. We also tested the hypothesis that BBS-2, a specific inhibitor of iNOS, would impair NO formation after burn. Thirteen female sheep were randomized into burn injury and smoke inhalation (n = 5, group 1), burn and smoke treated with BBS-2 (n = 3, group 2), and sham (saline treatment, no injury) (n = 5, group 3). All the animals, including the sham-injury group, were mechanically ventilated for 48 h. Samples of nonburned skin and plasma were collected from each animal, and levels of NO and its metabolites were evaluated using a NO chemiluminescent detector. Nitrotyrosine and iNOS expression were determined in the skin by Immunoperoxidase staining, and scoring of masked slides (epidermis, hair follicles, vessels, glands, and stroma) was performed. Skin NO and metabolites significantly increased in the burn and smoke injury group, and this was inhibited by BBS-2. Nitrotyrosine expression also increased significantly in the skin of burned animals. BBS-2 prevented the increase of NOx but not the increase of nitrotyrosine expression in skin. Plasma levels of NO increased in burned animals when compared with sham, but this increase was not significant. The increase of NO and its metabolites after burn in noninjured skin is followed by a significant increase in peroxynitrite, a potent cytotoxic mediator.
Department of Surgery, Shriners Hospital for Children, Galveston, Texas 77555, USA.
Gisele V
GV
Oliveira
Katsumi
K
Shimoda
Perenlei
P
Enkhbaatar
Jeff
J
Jodoin
A S
AS
Burke
D L
DL
Chinkes
Hal K
HK
Hawkins
David N
DN
Herndon
Lillian
L
Traber
Daniel
D
Traber
Kazunori
K
Murakami
D000818:Animals; D002056:Burns / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D012016:Reference Values; D012756:Sheep; D012867:Skin / Q000473:pathology; D012879:Skin Physiological Phenomena; D015208:Smoke Inhalation Injury / Q000473:pathology / Q000503:physiopathology*
D009569:Nitric Oxide