Reduction of 5-fluorouracil-induced toxicity by Sarcodon aspratus polysaccharides in Lewis tumor-bearing mice

Int J Biol Macromol. 2020 Nov 15:163:232-239. doi: 10.1016/j.ijbiomac.2020.05.004. Epub 2020 Jun 17.

Abstract

5-Fluorouracil (5-Fu) is an effective anticarcinogenic agent, however, continuous use of 5-Fu may cause severe side effects. The goal of this study was to investigate the effectiveness of Sarcodon aspratus polysaccharides (SATP) in alleviating 5-Fu-induced toxicity in Lewis tumor-bearing mice. Lewis tumor-bearing mice were treated with saline, SATP, 5-Fu or 5-Fu + SATP. The results indicated that compared to the 5-Fu group, the 5-Fu + SATP group showed effective amelioration of the liver, kidney and small intestine injury caused by 5-Fu and decreases in the levels of related biochemical indicators, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT) and urea nitrogen (BUN). Additionally, the combination therapy enhanced the quality of life and immune organ indexes of mice. Further mechanistic studies indicated that the 5-Fu + SATP group showed a decrease in hepatotoxicity caused by 5-Fu via a reduction in the levels of interleukin-1β (IL-1β), an increase in the expression of Bcl-2 and decreases in the expression of p-p38, p-JNK and Bax. Collectively, the results indicated that SATP could significantly alleviate the toxicity of 5-Fu in Lewis tumor-bearing mice and showed the hepatoprotective capability of SATP via its effect on the expression levels of inflammatory factors and components of the MAPK/P38/JNK pathway, which shows that it may be a potential adjuvant for the chemotherapeutic drug 5-Fu in cancer treatment.

Keywords: 5-Fluorouracil; Anti-inflammation; Antiapoptosis; Attenuated; Polysaccharides; Sarcodon aspratus.

MeSH terms

  • Animals
  • Basidiomycota / chemistry*
  • Carcinoma, Lewis Lung
  • Cell Line, Tumor
  • Disease Models, Animal
  • Drug Antagonism
  • Fluorouracil / pharmacology*
  • Fungal Polysaccharides / chemistry*
  • Fungal Polysaccharides / pharmacology*
  • Immunohistochemistry
  • Interleukin-1beta / blood
  • Male
  • Mice
  • Tumor Burden
  • Xenograft Model Antitumor Assays

Substances

  • Fungal Polysaccharides
  • IL1B protein, mouse
  • Interleukin-1beta
  • Fluorouracil

Supplementary concepts

  • Sarcodon aspratus