Phosalone-induced inflammation and oxidative stress in the colon: Evaluation and treatment

World J Gastroenterol. 2016 Jun 7;22(21):4999-5011. doi: 10.3748/wjg.v22.i21.4999.

Abstract

Aim: To investigate the side effects of phosalone on intestinal cells and to evaluate benefits of ellagic acid (EA) as a remedy.

Methods: In order to conduct an in vivo study, a rat model was used. The rats were divided into ten groups based on the materials used in the experiment and their dosage. The first group was fed normally. The second group was administered EA through gavage. Next Four groups were given (1/3, 1/5, 1/10, 1/20) LD50 phosalone; an organophosphorus compound. The last four groups received (1/3, 1/5, 1/10, 1/20) LD50 phosalone and of EA. After one month, the rats were sacrificed and their colon cells were examined to evaluate the level of inflammation, proteins and oxidative stress markers.

Results: The results of this research show that phosalone elevates oxidative stress and changes the level of tumor necrosis factor-a (TNF-α), interlukin-6β (IL-6β) and nuclear factor (NF)-κB proteins. EA administration reduced phosalone toxicity and changed oxidative stress and inflammatory markers for all phosalone doses. Overall changes in reduction of TNF-α (230.47 ± 16.55 pg/mg protein vs 546.43 ± 45.24 pg/mg protein, P < 0.001), IL-6β (15.85 ± 1.03 pg/mg protein vs 21.55 ± 1.3 pg/mg protein, P < 0.05), and NF-κB (32.47 ± 4.85 pg/mg protein vs 51.41 ± 0.71 pg/mg protein, P < 0.05) manifest that the efficacy of EA is more viable for 1/3 LD50 dose of phosalone. Furthermore, EA is effective to counteract the negative outcomes of oxidative stress. When EA was used to treat 1/3 LD50 of phosalone's side effects, it improved the level of AChE activity (48.5% ± 6% vs 25% ± 7%, P < 0.05), TTM (0.391 ± 0.008 mmol/L vs 0.249 ± 0.032 mmol/L, P < 0.05), FRAP (46.04 ± 5.005 μmol/L vs 18.22 ± 1.9 μmol/L, P < 0.01) and MPO (0.222 ± 0.019 U/mg protein vs 0.387 ± 0.04 U/mg protein, P < 0.05).

Conclusion: This research highlights that EA is effective to alleviate the side effects of phosalone by reducing the level of oxidative stress and inflammatory proteins.

Keywords: Colon; Ellagic acid; Inflammation; Organophosphorus; Oxidative stress; Phosalone.

MeSH terms

  • Acetylcholinesterase / metabolism
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Biomarkers / metabolism
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colitis / metabolism
  • Colitis / pathology
  • Colon / drug effects*
  • Colon / metabolism
  • Colon / pathology
  • Cytokines / metabolism
  • Cytoprotection
  • Disease Models, Animal
  • Ellagic Acid / pharmacology*
  • GPI-Linked Proteins / metabolism
  • Inflammation Mediators / metabolism
  • Lipid Peroxidation / drug effects
  • Male
  • NF-kappa B / metabolism
  • Organothiophosphorus Compounds*
  • Oxidative Stress / drug effects*
  • Peroxidase / metabolism
  • Rats, Wistar
  • Sulfhydryl Compounds / metabolism
  • Thiobarbituric Acid Reactive Substances / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Biomarkers
  • Cytokines
  • GPI-Linked Proteins
  • Inflammation Mediators
  • NF-kappa B
  • Organothiophosphorus Compounds
  • Sulfhydryl Compounds
  • Thiobarbituric Acid Reactive Substances
  • Ellagic Acid
  • phosalone
  • Peroxidase
  • Acetylcholinesterase
  • Ache protein, rat