Exogenous Biliverdin Improves the Function of Lung Grafts From Brain Dead Donors in Rats

Abstract

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-α 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)-κB in lung grafts. Conclusion Biliverdin exerts protective effects on lung grafts from BD donors through anti-inflammatory, antioxidant, and anti-apoptotic mechanisms.