Synthetic oligopeptides related to the [beta]-subunit of human chorionic gonadotropin attenuate inflammation and liver damage after (trauma) hemorrhagic shock and resuscitation.
Severe hemorrhagic shock (HS) followed by resuscitation induces a massive inflammatory response, which may culminate into systemic inflammatory response syndrome, multiple organ dysfunction syndrome, and, finally, death. Treatments that effectively prevent this inflammation are limited so far. In a previous study, we demonstrated that synthetic oligopeptides related to the primary structure of human chorionic gonadotropin (HCG) can inhibit the inflammatory response and mortality that follow high-dose LPS-induced inflammation. Considering this powerful anti-inflammatory effect, we investigated whether administration of similar synthetic HCG-related oligopeptides (LQGV, AQGV, LAGV) during HS were able to attenuate the inflammatory response associated with this condition. Hemorrhagic shock was induced in rats for 60 min by blood withdrawal until a MAP of 40 mmHg was reached. Rats received a single injection with one of the hCG-related oligopeptides (LQGV, AQGV or LAGV) or 0.9% NaCl solution as control 30 min after induction of HS. Treatment with LQGV, AQGV, or LAGV prevented systemic release of TNF-[alpha] and IL-6 and was associated with reduced TNF-[alpha], IL-6, and E-selectin mRNA transcript levels in the liver. LQGV treatment prevented neutrophil infiltration into the liver and was associated with reduced liver damage. Our data suggest that HCG-related oligopeptides, in particular LQGV, have therapeutic potential by attenuating the life-threatening inflammation and organ damage that is associated with (trauma) HS and resuscitation.
van den Berg
H Rogier
HR
Department of Surgery, Laboratory for Experimental Surgery, Erasmus MC, Rotterdam, The Netherlands.
Khan
Nisar A
NA
van der Zee
Marten
M
Bonthuis
Fred
F
IJzermans
Jan N M
JN
Dik
Willem A
WA
de Bruin
Ron W F
RW
Benner
Robbert
R
D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D019040:E-Selectin / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014947:Wounds and Injuries / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D006063:Chorionic Gonadotropin; D019040:E-Selectin; D015850:Interleukin-6; D009842:Oligopeptides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha