Evaluation of the therapeutic activity of melatonin and resveratrol in Inflammatory Bowel Disease: A longitudinal PET/CT study in an animal model

Int J Pharm. 2019 Dec 15:572:118713. doi: 10.1016/j.ijpharm.2019.118713. Epub 2019 Oct 5.

Abstract

Inflammatory Bowel Disease (IBD) is a group of chronic disorders of the gastrointestinal tract, which two main types are Crohn's disease and ulcerative colitis. Although conventional therapeutic strategies have demonstrated to be effective in the IBD treatment, it is necessary to incorporate novel therapeutic agents that target other mechanisms involved in the pathogenesis of the disease, such as oxidative stress. For this reason, the efficacy in vivo of two antioxidant compounds, melatonin and resveratrol, has been investigated in an animal model of TNBS (2, 4, 6-trinitrobenzenesulfonic acid) induced colitis. PET/CT (Positron emission tomography/Computer Tomography) scans were performed to assess disease activity and evaluate treatment response. SUVmax (Standardized Uptake Value) values, body weight changes and histological evaluation were used as inflammatory indices to measure the efficacy of both treatments. SUVmax values increased rapidly after induction of colitis, but after the beginning of the treatment (day 3) a statistically significant decrease was observed on days 7 and 10 in treated animals compared to the non-treated group. This remission of the disease was also confirmed by histological analysis of the colon tissue using the Nancy histological index (p value < 0.05 for differences between non-treated and both groups of treated animals). Moreover, statistical analysis showed a correlation (R2 = 65.52%) between SUVmax values and weight changes throughout the treatment. Overall, this study demonstrates the potential of resveratrol, and melatonin in lower extent, as therapeutic agents in the IBD treatment.

Keywords: ABTS; Inflammatory Bowel Disease; Melatonin; Rat model; Resveratrol; TNBS-induced colitis; [(18)F]FDG PET.

MeSH terms

  • Animals
  • Antioxidants / administration & dosage*
  • Colitis / chemically induced
  • Colitis / diagnostic imaging
  • Colitis / drug therapy*
  • Colitis / pathology
  • Colon / diagnostic imaging
  • Colon / drug effects
  • Colon / pathology
  • Melatonin / administration & dosage*
  • Positron Emission Tomography Computed Tomography
  • Rats, Sprague-Dawley
  • Resveratrol / administration & dosage*
  • Trinitrobenzenesulfonic Acid

Substances

  • Antioxidants
  • Trinitrobenzenesulfonic Acid
  • Melatonin
  • Resveratrol