Phytic acid improves intestinal mucosal barrier damage and reduces serum levels of proinflammatory cytokines in a 1,2-dimethylhydrazine-induced rat colorectal cancer model

Br J Nutr. 2018 Jul;120(2):121-130. doi: 10.1017/S0007114518001290.

Abstract

Phytic acid (PA) has been demonstrated to have a potent anticarcinogenic activity against colorectal cancer (CRC). Defects of the intestinal mucosal barrier and inflammation processes are involved in the development and progression of CRC. In the present study, we evaluated the effect of PA on the intestinal mucosal barrier and proinflammatory cytokines. After a 1-week acclimatisation period, sixty Wistar male rats were divided into the following five groups, with twelve rats per group: the control group (CG), model group (MG), low-PA-dose group (0·25 g/kg per d), middle-PA-dose group (0·5 g/kg per d), and high-PA-dose group (1 g/kg per d). 1,2-Dimethylhydrazine (DMH) at a dosage of 30 mg/kg of body weight was injected weekly to induce CRC for 18 weeks. We examined the expression of genes related to the intestinal mucosal barrier in the model. The results demonstrated that tumour incidence was decreased following PA treatment. The mRNA and protein expression of mucin 2 (MUC2), trefoil factor 3 (TFF3) and E-cadherin in the MG were significantly lower than those in the CG (P<0·05). The mRNA and protein expression of claudin-1 in the MG were significantly higher than those in the CG (P<0·05). PA elevated the mRNA and protein expression of MUC2, TFF3 and E-cadherin, and diminished the mRNA and protein expression of claudin-1. Furthermore, PA decreased serum levels of proinflammatory cytokines, which included TNF-α, IL-1β and IL-6. In conclusion, this study suggests that PA has favourable effects on the intestinal mucosal barrier and may reduce serum proinflammatory cytokine levels.

Keywords: CG control group; CRC colorectal cancer; D-LA D-lactate; DMH 1; HPG high-phytic acid-dose group; LPG low-phytic acid-dose group; LPS lipopolysaccharide; MG model group; MPG middle-phytic acid-dose group; MUC2 mucin 2; PA phytic acid; TFF3 trefoil factor 3; 2-dimethylhydrazine; Colorectal cancer; Intestinal mucosal barrier; Phytic acid; Proinflammatory cytokines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1,2-Dimethylhydrazine / chemistry
  • Animals
  • Body Weight
  • Cadherins / metabolism
  • Claudin-1 / metabolism
  • Colon / metabolism
  • Colorectal Neoplasms / blood*
  • Colorectal Neoplasms / chemically induced
  • Colorectal Neoplasms / metabolism
  • Cytokines / blood*
  • Disease Models, Animal
  • Disease Progression
  • Inflammation
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / metabolism
  • Lactic Acid / blood
  • Lipopolysaccharides / blood
  • Male
  • Mucin-2 / metabolism
  • Phenotype
  • Phytic Acid / pharmacology*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Trefoil Factor-3 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • CDH1 protein, rat
  • Cadherins
  • Claudin-1
  • Cytokines
  • Il6 protein, rat
  • Interleukin-1beta
  • Interleukin-6
  • Lipopolysaccharides
  • Muc2 protein, rat
  • Mucin-2
  • RNA, Messenger
  • TFF3 protein, rat
  • Trefoil Factor-3
  • Tumor Necrosis Factor-alpha
  • Lactic Acid
  • Phytic Acid
  • 1,2-Dimethylhydrazine