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| Content Provider | PubMed Central |
|---|---|
| Author | Squadrito, Francesco Altavilla, Domenica Squadrito, Giovanni Campo, Giuseppe M. Ioculano, Mariapatrizia Ammedolia, Letteria Arlotta, Mariarita Saitta, Antonino Caputi, Achille P. |
| Copyright Year | 1997 |
| Abstract | The aim of our study was to investigate the effects of recombinant human granulocyte-colony stimulating factor in a rat model of splanchnic ischaemia-reperfusion injury. Male anaesthetized rats were subjected to clamping of the splanchnic arteries for 45 min. This surgical procedure resulted in an irreversible state of shock (splanchnic artery occlusion shock; SAO shock). Sham operated animals were used as controls. Survival rate, serum tumour necrosis factor-α (TNF-α), neutrophil count, bone marrow myeloid precursor cells, myeloperoxidase activity (MPO; studied as a quantitative means to assess leukocyte accumulation), mean arterial blood pressure and the responsiveness of aortic rings to phenylephrine (PE, 1 nM–10 μM) were studied. SAO shocked rats had a decreased survival rate (0% at 4 h of reperfusion, while sham shocked rats survived more than 4 h), increased serum levels of TNF-α (201±10 u ml−1; sham shocked rats=undetectable), neutropenia, enhanced MPO activity in the ileum (0.11±0.06 u × 10−3 g−1 tissue; sham shocked rats=0.02±0.001 u × 10−3 g−1 tissue) and in the lung (1.5±0.2 u × 10−3 g−1 tissue; sham shocked rats=0.19±0.05 u × 10−3 g−1 tissue) and unchanged bone marrow myeloid precursor cells. Furthermore aortic rings from shocked rats showed a marked hyporeactivity to PE. Administration of recombinant human granulocyte colony stimulating factor (rh G-CSF; 5, 10 and 20 μg kg−1 5 min following the release of occlusion) increased in a dose-dependent manner survival rate (90% at 4 h of reperfusion with the dose of 20 u × 10−3 g kg−1), reduced serum TNF-α (13±5 u ml−1) and MPO activity in the ileum (0.065±0.002 u × 10−3 g−1 tissue) and in the lung (0.7±0.03 μ g kg−1 tissue), improved neutropenia and mean arterial blood pressure but did not modify bone marrow myeloid progenitor cells. Furthermore rh G-CSF, either in vivo or in vitro (200 nM for 1 h in the organ bath), restored to control values the hyporeactivity to PE. Finally rh G-CSF potently inhibited the activity of inducible nitric oxide synthase in peritoneal macrophages activated with endotoxin. Our results suggest that rh G-CSF protects against splanchnic ischaemia reperfusion injury by a mechanism(s) that does not depend upon its haematopoietic effects. |
| Related Links | http://dx.doi.org/10.1038/sj.bjp.0700904 |
| Ending Page | 339 |
| Page Count | 7 |
| Starting Page | 333 |
| File Format | |
| ISSN | 00071188 |
| Journal | British Journal of Pharmacology |
| Issue Number | 2 |
| Volume Number | 120 |
| Language | English |
| Publisher Date | 1997-01-01 |
| Access Restriction | Open |
| Subject Keyword | Pharmacology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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