High-fructose in drinking water initiates activation of inflammatory cytokines and testicular degeneration in rat

Toxicol Mech Methods. 2019 Mar;29(3):224-232. doi: 10.1080/15376516.2018.1543745. Epub 2019 Jan 15.

Abstract

The increased consumption of high-fructose in diet may contribute to high prevalence of metabolic syndrome in the world. The influence of high-fructose diet on male reproductive system has been poorly documented. In this study, we investigated the effects of dietary high-fructose on the expression of inflammatory cytokines in association with certain testicular proteins and sex hormones in the testis of rats. Fructose was given to the rats as 20% solution (7.8 mg/kg) in drinking water for 15 weeks. Dietary high-fructose caused testicular degeneration, also decreased testicular concentration of testosterone and right testis absolute weight. This dietary intervention increased iNOS and TNF-α mRNAs as well as iNOS, NF-κB, and p-NF-κβ proteins, but decreased IL-10 and IL-6 mRNAs expressions, in testicular samples of rats. Moreover, testicular TNF-α, IL-1β, and iNOS and plasma IL-1β levels were significantly increased in rats fed with fructose. A marked increase in the expression level of IGF-1R protein was considered in testicular tissue of fructose-treated rats. The expression intensities of c-kit, claudin-1, and pan-cadherin were comparable in seminiferous tubules of control and fructose-treated rats. In conclusion, high-fructose intake of rats leads to activation of inflammatory cytokines, which is accompanied by testicular degeneration. These changes could be responsible for hormonal dysfunction with low intra-testicular testosterone level, which could be relevant to male infertility.

Keywords: Dietary fructose; IGF-1R; inflammatory cytokines; testicular degeneration; testosterone.

MeSH terms

  • Animals
  • Cytokines / genetics*
  • Dietary Exposure / analysis*
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Drinking Water
  • Fructose / toxicity*
  • Gene Expression / drug effects*
  • Male
  • Organ Size / drug effects
  • Rats, Wistar
  • Testis / drug effects*
  • Testis / immunology
  • Testis / pathology*
  • Up-Regulation

Substances

  • Cytokines
  • Drinking Water
  • Fructose