title: Pyrrolidine dithiocarbamate modulates HSP70, iNOS, and apoptosis during hemorrhagic shock resuscitation in rats.
abstract: BACKGROUND
  The aim of this study is to evaluate whether hemorrhage and resuscitation affect liver, intestinal, and renal expressions of heat shock protein 70 (HSP70), inducible nitric oxide synthase (iNOS), and apoptosis indexes (TUNEL, caspase-3 activation) and whether the expression of these proteins can be modulated by pyrrolidine dithiocarbamate (PDTC) after a nonlethal hemorrhagic shock (HS) in rats.
  
  
  METHODS
  Forty rats were randomized into four groups: sham-operated, only HS, HS/resuscitation with blood plus normal saline (NS), and HS/resuscitation with blood/NS plus PDTC, 15 mg/kg body weight, intravenously. Rats were subjected to HS by blood removal to a mean arterial pressure of 35-40 mmHg through the femoral artery. After 1 hr of shock, the animals were resuscitated according to the experimental protocol. HSP70, iNOS, cleaved caspase-3 expression, and TUNEL were analyzed in liver, small intestine, and kidney 3 hr after resuscitation.
  
  
  RESULTS
  HS upregulated HSP70, iNOS, cleaved caspase-3 expression, and induced apoptosis (TUNEL) (p < .05 to < .001). Resuscitation was not associated with further increase of their expressions. The administration of PDTC during resuscitation decreased liver, intestinal, and renal activation of iNOS and apoptosis indexes (p < .05 to < .001), and was associated with further increase in HSP70 expression (p < .05).
  
  
  CONCLUSIONS
  Our results show that HS resuscitation with PDTC modulates several signaling pathways (HSP70, iNOS, TUNEL, and caspase-3) in a rat model. The results suggest that PDTC administration--by reducing apoptosis and iNOS expression--may have a potential role in minimizing organ damage after severe hemorrhage.
authors.affiliation: Anestesiologia e Rianimazione, Dipartimento di Discipline Medico-Chirurgiche, Università di Torino, Torino, Italia. paolo.cotogni@unito.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Cotogni
authors.forename: Roberto
authors.initials: R
authors.lastname: Bini
authors.forename: Antonella
authors.initials: A
authors.lastname: Trombetta
authors.forename: Giorgio
authors.initials: G
authors.lastname: Olivero
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D004789:Enzyme Activation; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D012151:Resuscitation / Q000379:methods*; D012771:Shock, Hemorrhagic / Q000188:drug therapy / Q000503:physiopathology*; D013859:Thiocarbamates / Q000494:pharmacology* / Q000627:therapeutic use; D015854:Up-Regulation
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D018840:HSP70 Heat-Shock Proteins; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D053148:Caspase 3