title: Protective Effects of Simvastatin Against Alendronate-Induced Gastric Mucosal Injury in Rats.
abstract: BACKGROUND
  It has been reported that simvastatin, a statin commonly prescribed for its anti-inflammatory and antioxidant effects, has gastroprotective effects in indomethacin and ethanol-induced gastric ulcers. However, the effects of simvastatin on alendronate-induced gastric mucosal injury remain unexplored.
  
  
  OBJECTIVE
  This study investigated the use of simvastatin for the treatment of alendronate-induced gastric ulcers in rats.
  
  
  METHODS
  Female rats were pretreated with vehicle or simvastatin (20 and 60 mg/kg p.o.). After 1 h, the rats received alendronate (50 mg/kg p.o.). Simvastatin was administered once daily for 7 days, and from the fourth day of simvastatin treatment, alendronate was administered once daily for 4 days. On the final day of treatment, 4 h after alendronate administration, animals were euthanized, their stomachs were removed, and gastric damage was measured. Samples of the stomach were fixed in 10 % formalin immediately after their removal for subsequent histopathological assessment. Unfixed samples were weighed, frozen at -80 °C until assayed for glutathione (GSH), malondialdehyde (MDA), and cytokine levels and myeloperoxidase (MPO) activity. A third group was used to measure mucus and gastric secretion.
  
  
  RESULTS
  Pretreatment with simvastatin prevented alendronate-induced macroscopic gastric damage and reduced the levels of MDA and GSH, TNF-α and IL-1β, MPO activity, and mucus levels, in the stomach.
  
  
  CONCLUSIONS
  This study demonstrates the protective effects of simvastatin against alendronate-induced gastric ulceration. Maintenance of mucosal integrity, inhibition of neutrophil activity, and reduced oxidative stress associated with decreased gastric acidity may explain the gastroprotective effects of simvastatin.
authors.affiliation: Post Graduation Program in Pharmacology, Medicinal Plant Research Center (NPPM), Federal University of Piauí, Teresina, PI, Brazil.
authors.forename: Nathalia S
authors.initials: NS
authors.lastname: Carvalho
authors.affiliation: Post Graduation Program in Biotechnology, Biotechnology and Biodiversity Center Research (BIOTEC), Federal University of Piauí, Parnaíba, PI, Brazil.
authors.forename: Mônica M
authors.initials: MM
authors.lastname: Silva
authors.affiliation: Laboratory of Pharmacology of Inflammation and Cancer (LAFICA), Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Renan O
authors.initials: RO
authors.lastname: Silva
authors.affiliation: Laboratory of Pharmacology of Inflammation and Cancer (LAFICA), Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Lucas A D
authors.initials: LA
authors.lastname: Nicolau
authors.affiliation: Post Graduation Program in Biotechnology, Biotechnology and Biodiversity Center Research (BIOTEC), Federal University of Piauí, Parnaíba, PI, Brazil.
authors.forename: Thiago S L
authors.initials: TS
authors.lastname: Araújo
authors.affiliation: Post Graduation Program in Pharmacology, Medicinal Plant Research Center (NPPM), Federal University of Piauí, Teresina, PI, Brazil.
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Costa
authors.affiliation: Post Graduation Program in Biotechnology, Biotechnology and Biodiversity Center Research (BIOTEC), Federal University of Piauí, Parnaíba, PI, Brazil.
authors.forename: Nayara A
authors.initials: NA
authors.lastname: Sousa
authors.affiliation: Post Graduation Program in Biotechnology, Biotechnology and Biodiversity Center Research (BIOTEC), Federal University of Piauí, Parnaíba, PI, Brazil.
authors.forename: Luan K M
authors.initials: LK
authors.lastname: Souza
authors.affiliation: Laboratory of Pharmacology of Inflammation and Cancer (LAFICA), Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Pedro M G
authors.initials: PM
authors.lastname: Soares
authors.affiliation: Post Graduation Program in Pharmacology, Medicinal Plant Research Center (NPPM), Federal University of Piauí, Teresina, PI, Brazil. jandvenes@ufpi.edu.br.|Post Graduation Program in Biotechnology, Biotechnology and Biodiversity Center Research (BIOTEC), Federal University of Piauí, Parnaíba, PI, Brazil. jandvenes@ufpi.edu.br.|BIOTEC/LAFFEX/UFPI, Av. São Sebastião, no. 2819, Parnaíba, PI, CEP 64202-020, Brazil. jandvenes@ufpi.edu.br.
authors.forename: Jand Venes R
authors.initials: JV
authors.lastname: Medeiros
mesh_terms: D019386:Alendronate / Q000633:toxicity*; D000818:Animals; D050071:Bone Density Conservation Agents / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D009195:Peroxidase / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology*; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D050071:Bone Density Conservation Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D019821:Simvastatin; D009195:Peroxidase; D005978:Glutathione; D019386:Alendronate
keywords: Anti-inflammatory; Antioxidant; Biphosphonate; Gastric damage; Simvastatin