Effect of Boron on Thymic Cytokine Expression, Hormone Secretion, Antioxidant Functions, Cell Proliferation, and Apoptosis Potential via the Extracellular Signal-Regulated Kinases 1 and 2 Signaling Pathway

J Agric Food Chem. 2017 Dec 27;65(51):11280-11291. doi: 10.1021/acs.jafc.7b04069. Epub 2017 Dec 18.

Abstract

Boron is an essential trace element in animals. Appropriate boron supplementation can promote thymus development; however, a high dose of boron can lead to adverse effects and cause toxicity. The influencing mechanism of boron on the animal body remains unclear. In this study, we examined the effect of boron on cytokine expression, thymosin and thymopoietin secretion, antioxidant function, cell proliferation and apoptosis, and extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathway in the thymus of rats. We found that supplementation with 10 and 20 mg/L boron to the drinking water significantly elevated levels of interleukin 2 (IL-2), interferon γ (IFN-γ), interleukin 4 (IL-4), and thymosin α1 in the thymus of rats (p < 0.05), increased the number of positive proliferating cell nuclear antigen (PCNA+) cells and concentrations of glutathione peroxidase (GSH-Px) and phosphorylated extracellular signal-regulated kinase (p-ERK) (p < 0.05), and promoted mRNA expression of PCNA and ERK1/2 in thymocytes (p < 0.05). However, the number of caspase-3+ cells and the expression level of caspase-3 mRNA were reduced (p < 0.05). Supplementation with 40, 80, and 160 mg/L boron had no apparent effect on many of the above indicators. In contrast, supplementation with 480 and 640 mg/L boron had the opposite effect on the above indicators in rats and elevated levels of pro-inflammatory cytokines, such as interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor α (TNF-α) (p < 0.05). Our study showed that supplementation of various doses of boron to the drinking water had a U-shaped dose-effect relationship with thymic cytokine expression, hormone secretion, antioxidant function, cell proliferation, and apoptosis. Specifically, supplementation with 10 and 20 mg/L boron promoted thymocyte proliferation and enhanced thymic functions. However, supplementation with 480 and 640 mg/L boron inhibited thymic functions and increased the number of apoptotic thymocytes, suggesting that the effects of boron on thymic functions may be caused via the ERK1/2 signaling pathway.

Keywords: ERK1/2 signaling pathway; antioxidant; boron; cytokine; proliferation and apoptosis; thymus.

MeSH terms

  • Animals
  • Antioxidants / metabolism*
  • Apoptosis / drug effects
  • Boron / pharmacology*
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cell Proliferation / drug effects
  • Cytokines / drug effects
  • Cytokines / genetics*
  • Cytokines / metabolism
  • Hormones / metabolism*
  • Male
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Thymus Gland / cytology*
  • Thymus Gland / drug effects*
  • Thymus Gland / metabolism

Substances

  • Antioxidants
  • Cytokines
  • Hormones
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Caspase 3
  • Boron