Exogenous biliverdin improves the function of lung grafts from brain dead donors in rats.
BACKGROUND
Biliverdin, a product of heme oxygenase-1 (HO-1), ameliorates the posttransplant functions of heart, kidney, and liver. In this study, we investigated the effects of biliverdin on lung grafts from brain dead (BD) rat donors.


METHODS
Male Wistar rats were randomly divided into 3 groups. The sham group (n = 7), did not undergo BD. Both donor and recipient rats in the BD biliverdin group (n = 8) were injected with biliverdin (35 mg/kg in 1 mL) intraperitoneally after confirmed BD and transplantation. In the BD group (n = 8), both donor and recipient rats received the same volume of saline (35 mg/kg in 1 mL) as the BD biliverdin group. All donor rats were observed for 1.5 hours before undergoing lung transplantation. Two hours after transplantation, we obtained blood and lung graft samples.


RESULTS
Biliverdin reversed the aggravation of Pa(O(2)) in recipients, reduced the grafts wet/dry ratio, decreased the severity of lung injury measured by histologic examination, reduced serum tumor necrosis factor-alpha and interleukin-8 levels and inhibited myeloperoxidase activity (MPO) in the grafts. Furthermore, it significantly decreased malonaldehyde levels and increased superoxide dismutase levels. Biliverdin reduced cell apoptosis, activated protein expression of biliverdin reductase, and inhibited expression of HO-1 and nuclear factor (NF)-kappaB in lung grafts.


CONCLUSIONS
Biliverdin exerts protective effects on lung grafts from BD donors through anti-inflammatory, antioxidant, and anti-apoptotic mechanisms.
Wang
J
J
Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Zhou
H-C
HC
Pan
P
P
Zhang
N
N
Li
W-Z
WZ
D000818:Animals; D017209:Apoptosis; D001663:Bilirubin / Q000097:blood; D001664:Biliverdine / Q000627:therapeutic use*; D001794:Blood Pressure; D001926:Brain Death; D004797:Enzyme-Linked Immunosorbent Assay; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000473:pathology; D016209:Interleukin-8 / Q000097:blood; D016040:Lung Transplantation / Q000379:methods / Q000473:pathology / Q000502:physiology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013047:Specific Pathogen-Free Organisms; D014139:Tracheostomy; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D016209:Interleukin-8; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; D001664:Biliverdine; D001663:Bilirubin