Citrus Flavanones Upregulate Thyrotroph Sirt1 and Differently Affect Thyroid Nrf2 Expressions in Old-Aged Wistar Rats

J Agric Food Chem. 2020 Aug 5;68(31):8242-8254. doi: 10.1021/acs.jafc.0c03079. Epub 2020 Jul 24.

Abstract

A growing population of elderly people consume citrus flavanones, naringenin, and hesperetin in the form of fruits or juices. Flavanones are bioactives with potent antioxidant properties and have potential in slowing down the aging process. Because flavanones exert controversial effects on pituitary-thyroid functioning, our study on the old-aged rat model aimed to elucidate the mechanism by which naringenin and hesperetin affect this axis. Naringenin and hesperetin increased the Sirt1 mRNA level by 91 and 71% (p < 0.05), which was followed by increased Sirt1 expression by 20 and 15% (p < 0.05), respectively. Only naringenin decreased thyroid-stimulating hormone expression by 20% (p < 0.05). Thyroid peroxidase protein expression was upregulated after naringenin or hesperetin by 62 and 43% (p < 0.05), respectively. Naringenin lowered mRNA levels of Tpo, Sod1, Sod2, Cat, and Nrf2 by 50, 32, 45, 35, and 42% (p < 0.05), respectively, and increased Gpx by 54% (p < 0.05), while hesperetin decreased Sod1 and Sod2 mRNA levels by 46 and 55% (p < 0.05), respectively. Naringenin increased the protein expressions of Nrf2 and SOD2 by 58 and 50% (p < 0.05), respectively, and decreased SOD1 expression by 48% (p < 0.05), while hesperetin protein decreased expressions of SOD1 and Nrf2 by 63 and 32% (p < 0.05), respectively. Altogether, our findings suggest that citrus flavanones contribute to restoring the impaired thyroid functioning in the old-aged rats.

Keywords: antioxidant enzymes; hesperetin; naringenin; thyroid peroxidase; thyroid ultrastructure.

MeSH terms

  • Aging / drug effects*
  • Aging / metabolism
  • Animals
  • Citrus / chemistry*
  • Flavanones / chemistry
  • Flavanones / pharmacology*
  • Fruit / chemistry
  • Male
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Rats
  • Rats, Wistar
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism*
  • Thyroid Gland / drug effects*
  • Thyroid Gland / metabolism

Substances

  • Flavanones
  • NF-E2-Related Factor 2
  • Plant Extracts
  • Sirtuin 1