Dietary zinc supplementation and methotrexate-induced small intestinal mucositis in metallothionein-knockout and wild-type mice

Abstract

Dietary Zn supplementation did not ameliorate MTX-induced small bowel damage, possibly signifying a deficiency in induction of MT by Zn. However, the presence of MT was able to reduce histological damage and neutrophil infiltration caused by MTX in the gut.

A Diet Containing Whey Protein, Glutamine, and TGFβ Modulates Gut Protein Metabolism During Chemotherapy-Induced Mucositis in Rats

“…However, different processes lead to intestinal mucositis: apoptosis, hypoproliferation [22], inflammatory response [23], altered gut protein metabolism [3,4], altered absorptive capacity [24], enhanced intestinal permeability [3], and bacteria proliferation and colonization [25]. Thus, innovative and integrated nutritional approaches are needed to target several of these altered processes [26][27][28]. We previously reported that methotrexate treatment alters intestinal mucosa and protein metabolism in rats with a decrease of protein synthesis and an increase of proteolysis mediated by lysosomal and calcium-dependent pathways [3,4].…”

Implications of high dietary zinc and intestinal metallothionein on the severity of methotrexate-induced mucositis

“…[1][2][3][4][5] In this issue of Cancer Biology & Therapy, Tran and co-workers investigate using dietary zinc (Zn) supplementation in mice to alleviate intestinal mucositis induced by methotrexate (MTX). 6 Numerous studies have demonstrated the benefits of Zn in wound repair 7 and as a dietary supplement to combat a variety of disorders including oesophageal dysplasia, peptic ulcers, Wilson disease and diarrhoea. [8][9][10] These benefits may arise from the many roles that Zn plays in repair and healing processes, as well as antioxidant and anti-apoptotic properties that may offer frontline protection against cytotoxic agents.…”

“…7,14 However, in the paper of Tran et al they found no improvement of MTX-induced intestinal damage after Zn supplementation. 6 In their study, damage was assessed by summing the scores from 11 independent histological criteria in the duodenum, jejunum and ileum, 1 and 3 d after single dose MTX administration. Myeloperoxidase (MPO), an indicator of oxidative stress after MTX, was also not influenced by Zn supplementation.…”

“…A major finding by Tran et al was that MTX-induced damage was more severe in all segments of the gut mucosa in the absence of metallothionein (MT). 6 MT belongs to a family of intracellular metal binding proteins, present in virtually all living organisms. [15][16][17] MTs are single chain polypeptides of 61-68 amino acids, and of which 20 are cysteine residues found in conserved sequence positions.…”

Evaluation of Modulatory Effect of Combination of Spondias Pinnata and Whey Preparation on Intestinal Antioxidants and Inflammatory Markers in Etoposide Induced Rat Model for Mucositis

“…Thus, innovative and integrated nutritional approaches are needed to target several of these altered processes. [6][7][8] Extensive experimental outcomes reported that many of the agents including growth factors like palifermin, NSAID, sucralfate, antifungal medicines etc. Drugs currently under investigation include keratinocyte growth factor, interleukin-1 and 11and TGF-b.…”