title: Epiisopiloturine hydrochloride, an imidazole alkaloid isolated from Pilocarpus microphyllus leaves, protects against naproxen-induced gastrointestinal damage in rats.
abstract: OBJECTIVE
  This study aimed to investigate the protective effect of epiisopiloturine hydrochloride (EPI), an imidazole alkaloid, on NAP-induced gastrointestinal damage in rats.
  
  
  METHODS
  Initially, rats were pretreated with 0.5% carboxymethylcellulose (vehicle) or EPI (3, 10 and 30mg/kg, p.o. or i.p., groups 3-5, respectively) twice daily, for 2days. After 1h, NAP (80mg/kg, p.o.) was given. The control group received only vehicle (group 1) or vehicle+naproxen (group 2). Rats were euthanized on 2nd day, 4h after NAP treatment. Stomachs lesions were measured. Samples were collected for histological evaluation and glutathione (GSH), malonyldialdehyde (MDA), myeloperoxidase (MPO), and cytokines levels. Moreover, gastric mucosal blood flow (GMBF) was evaluated.
  
  
  RESULTS
  EPI pretreatment prevented NAP-induced macro and microscopic gastric damage with a maximal effect at 10mg/kg. Histological analysis revealed that EPI decreased scores of damage caused by NAP. EPI reduced MPO (3.4±0.3U/mg of gastric tissue) and inhibited changes in MDA (70.4±8.3mg/g of gastric tissue) and GSH (246.2±26.4mg/g of gastric tissue). NAP increased TNF-α levels, and this effect was reduced by EPI pretreatment. Furthermore, EPI increased GMBF by 15% compared with the control group.
  
  
  CONCLUSIONS
  Our data show that EPI protects against NAP-induced gastric and intestinal damage by reducing pro-inflammatory cytokines, reducing oxidative stress, and increasing GMBF.
authors.affiliation: Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Lucas A D
authors.initials: LAD
authors.lastname: Nicolau
authors.affiliation: Post Graduation Program in Pharmacology, Federal University of Piauí, Teresina, PI, Brazil.
authors.forename: Nathalia S
authors.initials: NS
authors.lastname: Carvalho
authors.affiliation: Post Graduation Program in Morphofunctional Sciences, Department of Morphology, Faculty of Medicine, Federal University Ceará, Fortaleza, CE, Brazil.
authors.forename: Dvison M
authors.initials: DM
authors.lastname: Pacífico
authors.affiliation: Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Larisse T
authors.initials: LT
authors.lastname: Lucetti
authors.affiliation: Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Karoline S
authors.initials: KS
authors.lastname: Aragão
authors.affiliation: Post Graduation Program in Biotechnology, Federal University of Piauí, Parnaíba, Brazil.
authors.forename: Leiz M C
authors.initials: LMC
authors.lastname: Véras
authors.affiliation: Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Marcellus H L P
authors.initials: MHLP
authors.lastname: Souza
authors.affiliation: Post Graduation Program in Biotechnology, Federal University of Piauí, Parnaíba, Brazil.
authors.forename: José R S A
authors.initials: JRSA
authors.lastname: Leite
authors.affiliation: Post Graduation Program in Pharmacology, Federal University of Piauí, Teresina, PI, Brazil; Post Graduation Program in Biotechnology, Federal University of Piauí, Parnaíba, Brazil. Electronic address: jandvenes@ufpi.edu.br.
authors.forename: Jand Venes R
authors.initials: JVR
authors.lastname: Medeiros
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D007093:Imidazoles / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D008297:Male; D009288:Naproxen / Q000633:toxicity*; D032103:Pilocarpus; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D018515:Plant Leaves; D020011:Protective Agents / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000470:Alkaloids; D007093:Imidazoles; D010936:Plant Extracts; D020011:Protective Agents; C575691:epiisopiloturine; D009288:Naproxen; D015107:4-Butyrolactone
keywords: Epiisopiloturine; Gastrointestinal; Naproxen; Rat