title: Lack of effect of dopaminergic antagonists in a rodent model of peritoneal sepsis.
abstract: Central nervous system dopaminergic mechanisms have been implicated in the cytokine response to stress and sepsis. We here describe the effects of haloperidol or clozapine in the treatment of sepsis induced by cecal ligation and puncture. Male Wistar rats were subjected to the CLP procedure were treated with haloperidol or clozapine and plasma cytokines, myeloperoxidase activity, markers of organ injury and survival was analyzed. The addition of haloperidol or clozapine to basic support did not diminished hepatic, renal, pancreatic or muscular damage observed after sepsis. Neither haloperidol, nor clozapine, modulates pro and antiinflammatory cytokines after sepsis induction. In addition, haloperidol treatment did not diminished myeloperoxidase activity in the kidney, lung or liver, or altered BALF markers of lung damage or inflammatory infiltration. Our data did not support a role of haloperidol or clozapine as an immunomodulator agent in the treatment of sepsis in an animal model of peritonitis.
authors.affiliation: Laboratório de Fisiopatologia Experimental, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil.
authors.forename: Roberta Albino
authors.initials: RA
authors.lastname: Machado
authors.forename: Larissa
authors.initials: L
authors.lastname: Constantino
authors.forename: Márcio Rodrigo
authors.initials: MR
authors.lastname: Martins
authors.forename: Isabella Martins
authors.initials: IM
authors.lastname: de Albuquerque
authors.forename: Sérgio
authors.initials: S
authors.lastname: Menna-Barreto
authors.forename: Emílio
authors.initials: E
authors.lastname: Streck
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
authors.forename: Felipe
authors.initials: F
authors.lastname: Dal-Pizzol
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D003024:Clozapine / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D006220:Haloperidol / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation; D007416:Intestinal Perforation / Q000139:chemically induced / Q000473:pathology; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D010537:Peritoneum / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000139:chemically induced / Q000188:drug therapy*
chemical_list: D015415:Biomarkers; D018492:Dopamine Antagonists; D003024:Clozapine; D006220:Haloperidol