Intraperitoneal administration of methylene blue attenuates oxidative stress, increases peritoneal fibrinolysis, and inhibits intraabdominal adhesion formation.
BACKGROUND
Mounting evidence indicates that postoperative oxidative stress may be linked to decreased fibrinolytic activity and, subsequently, the development of intraabdominal adhesions. The goal of this study was to determine if methylene blue, a highly redox active dye that has been shown to inhibit adhesion formation (1) acts as an antioxidant in the postoperative peritoneum, and (2) subsequently affects fibrinolytic activity.


METHODS
Intraabdominal adhesions were surgically induced in rats receiving methylene blue (30 mg/kg) or vehicle (sterile water) intraperitoneally at surgery. At 24 h and 7 d following surgery, adhesion formation, oxidative stress, and peritoneal fibrinolytic activity were assessed.


RESULTS
Methylene blue did not affect adhesion formation at 24 h, but did induce a >50% regression in adhesions after 7 d (P < 0.05). Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and myeloperoxidase (MPO) activities, and 8-isoprostane and thiobarbituric acid-reactive substances were all significantly increased in peritoneal tissue samples (P < 0.05) by 24 h following surgery. Methylene blue inhibited NADPH oxidase by 98% and MPO activity by 78% in the 24 h tissue samples, and blunted the corresponding surgery-induced increases in tissue lipid and protein oxidation. Furthermore, methylene blue significantly increased (P < 0.05) fibrinolytic activity in peritoneal fluid at 24 h.


CONCLUSIONS
Methylene blue acts as an antioxidant in this experimental system and may reduce intraabdominal adhesion formation by enhancing peritoneal fibrinolytic activity following surgery.
Heydrick
Stanley J
SJ
Department of Surgery, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Reed
Karen L
KL
Cohen
Philip A
PA
Aarons
Cary B
CB
Gower
Adam C
AC
Becker
James M
JM
Stucchi
Arthur F
AF
D000005:Abdomen / Q000601:surgery*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001202:Ascitic Fluid / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005342:Fibrinolysis / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology*; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D000267:Tissue Adhesions / Q000378:metabolism / Q000517:prevention & control*