Ginkgo biloba extract (EGb 761) attenuates lung injury induced by intestinal ischemia/reperfusion in rats: roles of oxidative stress and nitric oxide.

AIM To investigate the effect of ginkgo biloba extract (EGb 761) on lung injury induced by intestinal ischemia/reperfusion (II/R). METHODS The rat model of II/R injury was produced by clamping the superior mesenteric artery for 60 min followed by reperfusion for 180 min. The rats were randomly allocated into sham, II/R, and EGb + II/R groups. In EGb + II/R group, EGb 761 (100 mg/kg per day) was given via a gastric tube for 7 consecutive days prior to surgery. Rats in II/R and sham groups were treated with equal volumes of the vehicle of EGb 761. Lung injury was assessed by light microscopy, wet-to-dry lung weight ratio (W/D) and pulmonary permeability index (PPI). The levels of malondialdehyde (MDA) and nitrite/nitrate (NO2(-)/NO3(-)), as well as the activities of superoxide dismutase (SOD) and myeloperoxidase (MPO) were examined. Western blot was used to determine the expression of inducible nitric oxide synthase (iNOS). RESULTS EGb 761 markedly improved mean arterial pressure and attenuated lung injury, manifested by the improvement of histological changes and significant decreases of pulmonary W/D and PPI (P < 0.05 or 0.01). Moreover, EGb 761 markedly increased SOD activity, reduced MDA levels and MPO activity, and suppressed NO generation accompanied by down-regulation of iNOS expression (P < 0.05 or 0.01). CONCLUSION The results indicate that EGb 761 has a protective effect on lung injury induced by II/R, which may be related to its antioxidant property and suppressions of neutrophil accumulation and iNOS-induced NO generation. EGb 761 seems to be an effective therapeutic agent for critically ill patients with respiratory failure related to II/R.

[1]  Kyung-Tae Lee,et al.  Preventive effect of Ginkgo biloba extract (GBB) on the lipopolysaccharide-induced expressions of inducible nitric oxide synthase and cyclooxygenase-2 via suppression of nuclear factor-kappaB in RAW 264.7 cells. , 2006, Biological & pharmaceutical bulletin.

[2]  I. Temel,et al.  The effects of ginkgo biloba extract on tissue adenosine deaminase, xanthine oxidase, myeloperoxidase, malondialdehyde, and nitric oxide in cisplatin-induced nephrotoxicity , 2006, Toxicology and industrial health.

[3]  Yuan Luo,et al.  Alzheimer's disease, the nematode Caenorhabditis elegans, and ginkgo biloba leaf extract. , 2006, Life sciences.

[4]  Ke-xuan Liu,et al.  [Study on sini decoction in treatment of intestinal ischemia-reperfusion injury in rats: mechanism relating to oxygen radical and bcl-2 protein]. , 2006, Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica.

[5]  I. Taitzoglou,et al.  Attenuation of intestinal ischemia/reperfusion induced liver and lung injury by intraperitoneal administration of (−)-Epigallocatechin-3-gallate , 2006, Free radical research.

[6]  Feihu Chen,et al.  Protective effect of total flavones of rhododendra on ischemic myocardial injury in rabbits. , 2006, The American journal of Chinese medicine.

[7]  L. Kabasakal,et al.  Hepatic fibrosis in biliary-obstructed rats is prevented by Ginkgo biloba treatment. , 2005, World journal of gastroenterology.

[8]  Xin-li Huang,et al.  Role of nitric oxide and peroxynitrite anion in lung injury induced by intestinal ischemia-reperfusion in rats. , 2003, World journal of gastroenterology.

[9]  R. Williamson,et al.  Differential expression of pulmonary nitric oxide synthase isoforms after intestinal ischemia-reperfusion. , 2003, Hepato-Gastroenterology.

[10]  T. Ohlsson,et al.  The Effect of Intestinal Ischemia and Reperfusion Injury on ICAM-1 Expression, Endothelial Barrier Function, Neutrophil Tissue Influx, and Protease Inhibitor Levels in Rats , 2002, Shock.

[11]  G. Schmid-Schönbein,et al.  Protease Inhibition in the Intestinal Lumen: Attenuation of Systemic Inflammation and Early Indicators of Multiple Organ Failure in Shock , 2002, Shock.

[12]  S. Hazinedaroglu,et al.  An assessment of the effect of Ginkgo Biloba EGb 761 on ischemia reperfusion injury of intestine. , 2002, Hepato-gastroenterology.

[13]  G. Fiskum,et al.  Neuroprotective effects of bilobalide, a component of the Ginkgo biloba extract (EGb 761), in gerbil global brain ischemia , 2001, Brain Research.

[14]  E. Deitch.  Role of the gut lymphatic system in multiple organ failure , 2001, Current opinion in critical care.

[15]  E. Mazzon,et al.  Protective effects of a new stable, highly active SOD mimetic, M40401 in splanchnic artery occlusion and reperfusion , 2001, British journal of pharmacology.

[16]  M. Yoshida,et al.  The role of cytokine‐induced neutrophil chemoattractant‐1 in neutrophil‐mediated remote lung injury after intestinal ischaemia/reperfusion in rats , 2000, Respirology.

[17]  E. Deitch,et al.  Inducible nitric oxide synthase gene knockout mice have increased resistance to gut injury and bacterial translocation after an intestinal ischemia-reperfusion injury , 2000, Critical care medicine.

[18]  A. Kettle,et al.  Biomarkers of myeloperoxidase-derived hypochlorous acid. , 2000, Free radical biology & medicine.

[19]  B. Diamond,et al.  Ginkgo biloba extract: mechanisms and clinical indications. , 2000, Archives of physical medicine and rehabilitation.

[20]  M. Caty,et al.  Attenuated nitric oxide synthase activity and protein expression accompany intestinal ischemia/reperfusion injury in rats. , 2000, Biochemical and biophysical research communications.

[21]  R. Sayers,et al.  Pulmonary nitric oxide metabolism following infrarenal aortic cross-clamp-induced ischaemia-reperfusion injury. , 2000, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[22]  Y. Siow,et al.  Inhibitory effect of Ginkgo biloba extract on the expression of inducible nitric oxide synthase in endothelial cells. , 1999, Biochemical pharmacology.

[23]  P. Ferdinandy,et al.  The protective effect of EGb 761 in isolated ischemic/reperfused rat hearts: a link between cardiac function and nitric oxide production. , 1999, Journal of cardiovascular pharmacology.

[24]  E. Deveci,et al.  Histopathological assessment of the prophylactic effect of gingko-biloba extract on intestinal ischemia-reperfusion injury. , 1999, Acta gastro-enterologica Belgica.

[25]  F. Clostre.  [Ginkgo biloba extract (EGb 761). State of knowledge in the dawn of the year 2000]. , 1999, Annales pharmaceutiques francaises.

[26]  Y. Yu,et al.  [The effect of intestinal ischemia/reperfusion on increased sensitivity to endotoxin and its potential mechanism]. , 1999, Zhonghua zheng xing shao shang wai ke za zhi = Zhonghua zheng xing shao shang waikf [i.e. waike] zazhi = Chinese journal of plastic surgery and burns.

[27]  L. Kim,et al.  Intestinal reperfusion-induced pulmonary edema is related to increased pulmonary inducible nitric oxide synthase activity. , 1998, Surgery.

[28]  H. Karamanoukian,et al.  Mucosal protection from intestinal ischemia-reperfusion reduces oxidant injury to the lung. , 1997, The Journal of surgical research.

[29]  S. Homer-Vanniasinkam,et al.  Post-ischaemic organ dysfunction: a review. , 1997, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[30]  L. Packer,et al.  Bio‐normalizer modulates interferon‐γ‐induced nitric oxide production in the mouse macrophage cell line RAW 264.7 , 1997, Biochemistry and molecular biology international.

[31]  A. Jenkins,et al.  Lipoxidation products as biomarkers of oxidative damage to proteins during lipid peroxidation reactions. , 1996, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[32]  W. Pryor,et al.  The chemistry of peroxynitrite: a product from the reaction of nitric oxide with superoxide. , 1995, The American journal of physiology.

[33]  K. Guice,et al.  Pulmonary microvascular injury following intestinal reperfusion. , 1994, New horizons.

[34]  L. Packer,et al.  The nitric oxide-scavenging properties of Ginkgo biloba extract EGb 761. , 1994, Biochemical and biophysical research communications.

[35]  K. Guice,et al.  Endotoxemia and remote organ injury following intestinal reperfusion. , 1994, The Journal of surgical research.

[36]  K. H. Kimbel,et al.  Ginkgo biloba , 1992, The Lancet.

[37]  J. Kleijnen,et al.  GINKGO BILOBA DRUG PROFILE , 1992 .

[38]  K. Rahbar,et al.  Idiopathic Cyclic Edema , 1988 .

[39]  K. Rahbar,et al.  [Idiopathic cyclic edema. The role of capillary hyperpermeability and its correction by Ginkgo biloba extract]. , 1986, Presse medicale.