The effect of budesonide on the expression of Ki-67 and PCNA and the apoptotic index in dogs with inflammatory bowel disease

Pol J Vet Sci. 2017 Dec;20(4):743-750. doi: 10.1515/pjvs-2017-0094.

Abstract

The aim of this study was to determine the effect of budesonide on the expression of Ki-67 and PCNA proliferative antigens and the apoptotic index in the course of inflammatory bowel disease (IBD) and to evaluate the applicability of these markers in monitoring IBD treatment in dogs. The experiment was performed on 28 dogs of different breeds and both sexes, with body weight of 6 to 20 kg, aged 6 to 10 years. The animals diagnosed with IBD were divided into four groups of 7 dogs each, including three experimental groups characterized by various severity of IBD and a control group. The dogs from the experimental groups were administered budesonide (Entocort, Astra-Zeneca, Sweden) in daily doses depending on body weight of animal - 1.0 mg (6-10 kg), 1.5 mg (11-15 kg) or 2.0 mg (16-20 kg) and control group dogs were orally administered empty gelatin capsules (placebo) for 30 days. The expression of Ki-67 and PCNA antigens was determined immunohistochemically, and the apoptotic index was expressed as the number of TUNEL-positive lamina propria cells in duodenal, jejunal and colonic mucosa before and after 30 days of budesonide therapy. The results of the study point to the limited applicability of Ki-67 and PCNA proliferation markers and high applicability of the apoptotic index in monitoring IBD progression and treatment in dogs. Budesonide exerted significant anti-apoptotic effects in canine patients with various severity of IBD, which indicates that next-generation glucocorticosteroids can be effectively used in the treatment of gastrointestinal diseases characterized by high values of the apoptotic index, including IBD.

Keywords: CNA; Ki-67; apoptotic index; budesonide; dogs; inflammatory bowel disease.

Publication types

  • Clinical Trial, Veterinary

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use
  • Apoptosis / drug effects*
  • Budesonide / therapeutic use*
  • Dog Diseases / drug therapy*
  • Dogs
  • Female
  • Gene Expression Regulation / drug effects
  • Inflammatory Bowel Diseases / drug therapy
  • Inflammatory Bowel Diseases / metabolism
  • Inflammatory Bowel Diseases / veterinary*
  • Ki-67 Antigen / genetics
  • Ki-67 Antigen / metabolism*
  • Male
  • Proliferating Cell Nuclear Antigen / genetics
  • Proliferating Cell Nuclear Antigen / metabolism*

Substances

  • Anti-Inflammatory Agents
  • Ki-67 Antigen
  • Proliferating Cell Nuclear Antigen
  • Budesonide