Use of growth-hormone-releasing peptide-6 (GHRP-6) for the prevention of multiple organ failure.
Novel therapies for the treatment of MOF (multiple organ failure) are required. In the present study, we examined the effect of synthetic GHRP-6 (growth hormone-releasing peptide-6) on cell migration and proliferation using rat intestinal epithelial (IEC-6) and human colonic cancer (HT29) cells as in vitro models of injury. In addition, we examined its efficacy when given alone and in combination with the potent protective factor EGF (epidermal growth factor) in an in vivo model of MOF (using two hepatic vessel ischaemia/reperfusion protocols; 45 min of ischaemia and 45 min of reperfusion or 90 min of ischaemia and 120 min of reperfusion). In vitro studies showed that GHRP-6 directly influenced gut epithelial function as its addition caused a 3-fold increase in the rate of cell migration of IEC-6 and HT29 cells (P<0.01), but did not increase proliferation ([3H]thymidine incorporation). In vivo studies showed that, compared with baseline values, ischaemia/reperfusion caused marked hepatic and intestinal damage (histological scoring), neutrophilic infiltration (myeloperoxidase assay; 5-fold increase) and lipid peroxidation (malondialdehyde assay; 4-fold increase). Pre-treatment with GHRP-6 (120 microg/kg of body weight, intraperitoneally) alone truncated these effects by 50-85% (all P<0.05) and an additional benefit was seen when GHRP-6 was used in combination with EGF (1 mg/kg of body weight, intraperitoneally). Lung and renal injuries were also reduced by these pre-treatments. In conclusion, administration of GHRP-6, given alone or in combination with EGF to enhance its effects, may provide a novel simple approach for the prevention and treatment of MOF and other injuries of the gastrointestinal tract. In view of these findings, further studies appear justified.
Cibrián
Danay
D
Center for Genetic Engineering and Biotechnology, Ave 31 e/158 & 190 Playa 10600, Havana, Cuba.
Ajamieh
Hussam
H
Berlanga
Jorge
J
León
Olga S
OS
Alba
Jose S
JS
Kim
Micheal J-T
MJ
Marchbank
Tania
T
Boyle
Joseph J
JJ
Freyre
Freya
F
Garcia Del Barco
Diana
D
Lopez-Saura
Pedro
P
Guillen
Gerardo
G
Ghosh
Subrata
S
Goodlad
Robert A
RA
Playford
Raymond J
RJ
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009102:Multiple Organ Failure / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D020556:Neutrophil Infiltration / Q000187:drug effects; D009842:Oligopeptides; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D014407:Tumor Cells, Cultured
D009842:Oligopeptides; D011994:Recombinant Proteins; C041048:growth hormone releasing hexapeptide; D004815:Epidermal Growth Factor; D013007:Growth Hormone-Releasing Hormone