Xiao-Min Yao1, Hui Chen, Yan Li. 1. Department of New Drug Development, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Abstract
AIM: Bicyclol is a synthetic anti-hepatitis drug with anti-oxidative property. The purpose of this study was to investigate the effect of bicyclol on hepatic ischemia/reperfusion (I/R) injury and related mechanisms. METHODS: Rats were subjected to 90 min of hepatic ischemia followed by reperfusion for 1, 3, 6 and 24 h. Three doses of bicyclol were orally administered before ischemia. Liver injury was evaluated by biochemical and histopathological examinations. Liver malondialdehyde (MDA), superoxide dismutase (SOD), nitric oxide (NO), inducible nitric oxide synthase (iNOS) and myeloperoxidase (MPO) contents, and plasma endotoxin levels were spectrophotometrically measured. The expressions of inflammatory and anti-inflammatory cytokines were detected by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Liver intercellular adhesion molecule-1 (ICAM-1) was examined by immunohistochemistry, and the expressions of nuclear factor (NF)-kappaB, inhibitor of NF-kappaB (IkappaB) and toll-like receptor 4 (TLR4) were determined by western blot. RESULTS: Bicyclol significantly inhibited the elevations of serum alanine aminotransferase, total bilirubin and plasma endotoxin levels, alleviated the formation of liver MDA and nitrite/nitrate, restored impaired antioxidant SOD, attenuated hepatic necrosis and neutrophil infiltration, and also improved the 7-day survival in I/R rats. Additionally, bicyclol markedly downregulated the overexpression of ICAM-1, modulated the expression of inflammatory/anti-inflammatory cytokines and inhibited the expression of NF-kappaB and TLR4 in I/R rats. CONCLUSION: Bicyclol had a remarkable protective effect on hepatic I/R injury, which was partially due to inhibiting the expression of TLR4 and NF-kappaB via its ability to attenuate oxidative stress and endotoxin.
AIM: Bicyclol is a synthetic anti-hepatitis drug with anti-oxidative property. The purpose of this study was to investigate the effect of bicyclol on hepatic ischemia/reperfusion (I/R) injury and related mechanisms. METHODS:Rats were subjected to 90 min of hepatic ischemia followed by reperfusion for 1, 3, 6 and 24 h. Three doses of bicyclol were orally administered before ischemia. Liver injury was evaluated by biochemical and histopathological examinations. Liver malondialdehyde (MDA), superoxide dismutase (SOD), nitric oxide (NO), inducible nitric oxide synthase (iNOS) and myeloperoxidase (MPO) contents, and plasma endotoxin levels were spectrophotometrically measured. The expressions of inflammatory and anti-inflammatory cytokines were detected by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Liver intercellular adhesion molecule-1 (ICAM-1) was examined by immunohistochemistry, and the expressions of nuclear factor (NF)-kappaB, inhibitor of NF-kappaB (IkappaB) and toll-like receptor 4 (TLR4) were determined by western blot. RESULTS:Bicyclol significantly inhibited the elevations of serum alanine aminotransferase, total bilirubin and plasma endotoxin levels, alleviated the formation of liver MDA and nitrite/nitrate, restored impaired antioxidant SOD, attenuated hepatic necrosis and neutrophil infiltration, and also improved the 7-day survival in I/R rats. Additionally, bicyclol markedly downregulated the overexpression of ICAM-1, modulated the expression of inflammatory/anti-inflammatory cytokines and inhibited the expression of NF-kappaB and TLR4 in I/R rats. CONCLUSION:Bicyclol had a remarkable protective effect on hepatic I/R injury, which was partially due to inhibiting the expression of TLR4 and NF-kappaB via its ability to attenuate oxidative stress and endotoxin.
Authors: Eman T Mehanna; Al-Shimaa A Ali; Fatma El-Shaarawy; Noha M Mesbah; Dina M Abo-Elmatty; Nora M Aborehab Journal: Molecules Date: 2021-12-08 Impact factor: 4.411