Abstract
BackgroundActivation of Kupffer cell (KC) is acknowledged as a key event in the initiation and perpetuation of bile duct warm ischemia/reperfusion injury. The inhibitory effect of gadolinium chloride (GdCl3) on KC activation shows potential as a protective intervention in liver injury, but there is less research with regard to bile duct injury.MethodsSixty-five male Sprague-Dawley rats (200–250 g) were randomly divided into three experimental groups: a sham group (n = 15), a control group (n = 25), and a GdCl3 group (n = 25). Specimen was collected at 0.5, 2, 6, 12 and 24 h after operation. Alanine aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin (TBIL) of serum were measured. Tumor necrosis factor-α (TNF-α), Capase-3 activity and soluble Fas (sFas) were detected. The pathologic changes of bile duct were observed. Immunochemistry for bile duct Fas was performed. Apoptosis of bile duct cells was evaluated by the terminal UDP nick end labeling assay.ResultsGdCl3 significantly decreased the levels of ALT, ALP and TBIL at 2, 6, 12, and 24 h, and increased serum sFas at 2, 6 and 12 h (P<0.05). TNF-α was lower in the GdCl3 group than in the control group at 2, 6, 12 and 24 h (P<0.05). Preadministration of GdCl3 significantly reduced the Caspase-3 activity and bile duct cell apoptosis at 2, 6, 12 and 24 h. After operation for 2, 6 and 12 h, the expression of Fas protein was lower in the GdCl3 group than in the control group (P<0.05).ConclusionsGdCl3 plays an important role in suppressing bile duct cell apoptosis, including decreasing ALT, ALP, TBIL and TNF-α; suppressing Fas-FasL-Caspase signal transduction during transplantation.
Highlights
Biliary complications remain a major cause of morbidity and mortality after orthotopic liver transplantation [1,2]
Those for ALT, alkaline phosphatase (ALP) and DBIL levels were significantly higher in the control group than in the sham group at all indicated time points (P,0.01); Bile duct function was evaluated with ATL, ALP and total bilirubin (TBIL), respectively
Serum tumor necrosis factor-a (TNF-a) and soluble Fas (sFas) levels As shown in Fig. 2, the serum level of TNF-a was markedly increased during warm ischemia/reperfusion, reaching a plateau 12 h after operation
Summary
Biliary complications remain a major cause of morbidity and mortality after orthotopic liver transplantation [1,2]. Hepatic artery thrombosis [3], prolonged cold injury time [1,2,4], warm ischemia/reperfusion injury [1,4,5], and immunological rejection [6,7] have all been variously associated with structural changes and functional lesions of the biliary tract following grafting Among these pathogenic factors, warm ischemia/reperfusion injury is recognized as the major cause of the early phase of biliary lesion development [1,8]. Our laboratory has established an orthotopic autologous rat liver transplantation model [18] This model simulates the entire process of clinical liver transplantation and avoids the effects of infection and immune suppression while accurately controlling bile duct warm ischemia/reperfusion time. The inhibitory effect of gadolinium chloride (GdCl3) on KC activation shows potential as a protective intervention in liver injury, but there is less research with regard to bile duct injury
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
