title: Effect of caspase inhibition on thymic apoptosis in hemorrhagic shock.
abstract: In hemorrhagic shock (HS) an increased thymic apoptosis (TA) was described. The aim of this study was to evaluate the effect of administration of the caspase inhibitor N-benzyloxy-carbonil-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK) during the resuscitation phase on TA, organ dysfunctions, and tumor necrosis factor (TNF)-alpha release in HS. Forty rats were randomly assigned to four groups: no HS/resuscitation (sham); HS/resuscitation with shed blood and normal saline (control); HS/resuscitation with shed blood and phosphate-buffered solution (PBS) (vehicle); and HS/resuscitation with shed blood and Z-VAD-FMK (inhibitor). Rats were subjected to HS by blood removal to a MAP of 35-40 mmHg. After a 1-h shock period, the animals were resuscitated according to the protocol. At 1 and 3 h after resuscitation, transaminases, creatinine, urea, lipase, TNF-alpha, and TA were evaluated. Our study showed that a nonlethal HS is early able to induce organ dysfunctions and increased TA. Administration of Z-VAD-FMK did not significantly decrease organ dysfunctions, while it induced a significant TNF-alpha release. TA was significantly reduced by Z-VAD-FMK after 1 h, but not after 3 h. Our results suggest that postinjury caspase inhibition does not attenuate organ dysfunctions, and also does not permanently reduce TA induced by HS and resuscitation in rats.
authors: Chirurgia d'Urgenza, Dipartimento di Discipline Medico-Chirurgiche, Universit à di Torino, Torino, Italy.
authors: Roberto
authors: R
authors: Bini
authors: Raffaele
authors: R
authors: Cursio
authors: Nathalie
authors: N
authors: Belhacene
authors: Jean
authors: J
authors: Giudicelli
authors: Bernard
authors: B
authors: Ferruà
authors: Giorgio
authors: G
authors: Olivero
authors: Patrick
authors: P
authors: Auberger
authors: Bernard
authors: B
authors: Mari
authors: Jean
authors: J
authors: Gugenheim
authors: Paolo
authors: P
authors: Cotogni
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000473:pathology*; D013950:Thymus Gland / Q000187:drug effects* / Q000473:pathology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D014409:Tumor Necrosis Factor-alpha; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D020169:Caspases