Beneficial effect of oral administration of zinc sulfate on 5-fluorouracil-induced gastrointestinal mucositis in rats

Eur Rev Med Pharmacol Sci. 2020 Nov;24(21):11365-11373. doi: 10.26355/eurrev_202011_23628.

Abstract

Objective: This experimental study explored the potential of oral zinc sulfate to protect the gut mucosa from 5-fluorouracil (5-FU)-induced degenerative lesions in Wistar rats.

Materials and methods: Female Wistar rats were used and divided into 2 interventional groups (Z with 6 animals and F with 5 animals) and one control group (M with 5 rats). After 2 hours of fasting, group Z received via oral gavage 1.5 ml of solution, corresponding to 15 mg zinc sulfate for 9 consecutive days. Groups F and M received only the vehicles. On day 3, 400 mg/kg of 5-FU was administered intraperitoneally to groups Z and F. Tissue samples were collected from the duodenum, jejunum, colon and liver. Histological assessment for each gastrointestinal tract segment was determined semi-quantitatively by rating 11 histological features from normal (0) to severe (3). The independent groups were analyzed using the Kruskal-Wallis test and the Mann-Whitney U-test, with a Bonferroni correction for alpha (p ≤ 0.016).

Results: In group F the jejunum was the most affected area with a mean histological score of 27 (25-32). In the Z group, significantly lower histological scores were obtained compared with group F (duodenum Z vs. F: U = 0, p = 0.004; jejunum Z vs. F: U = 0, p = 0.006 and colon: Z vs. F: U = 0, p = 0.005). Graded liver necro-inflammatory lesions were significantly lower in group Z compared with group F (U = 0, p = 0.004), suggesting fewer bacterial intestinal translocation processes.

Conclusions: Zinc sulfate has a beneficial role, decreasing the severity of gut mucosal injuries induced by 5-FU in Wistar rats.

MeSH terms

  • Administration, Oral
  • Animals
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / adverse effects*
  • Disease Models, Animal
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects*
  • Gastrointestinal Tract / drug effects*
  • Gastrointestinal Tract / pathology
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Inflammation / pathology
  • Mucositis / chemically induced
  • Mucositis / drug therapy*
  • Mucositis / pathology
  • Rats
  • Rats, Wistar
  • Zinc Sulfate / administration & dosage
  • Zinc Sulfate / pharmacology*

Substances

  • Antimetabolites, Antineoplastic
  • Zinc Sulfate
  • Fluorouracil