Effects of sulforaphane on D-galactose-induced liver aging in rats: Role of keap-1/nrf-2 pathway

Eur J Pharmacol. 2019 Jul 15:855:40-49. doi: 10.1016/j.ejphar.2019.04.043. Epub 2019 Apr 27.

Abstract

Aging; a biological phenomenon characterized by progressive decline in cellular functions, is considered as a major risk factor of various liver diseases that plays as an adverse prognostic role, thus increasing mortality rate. However, diet is the main environmental factor that has a major impact on the aging process whereas; sulforaphane (SFN), an isothiocyanate organosulfur compound in cruciferous vegetables, has been reported with myriad biological effects. In the present study, SFN antiaging properties were evaluated on D-galactose (D-Gal)-induced liver aging in rats. For this purpose, forty adult male Wistar rats were divided into five groups. All animals, except the normal control, were intraperitoneally injected with D-Gal (300 mg/kg/day for 5 days a week) for six consecutive weeks. In the hepatoprotective groups, animals received oral SFN (0.5, 1.0 and 2.0 mg/kg) for 6 weeks concurrently with D-GAL. SFN administration improved liver biomarkers through decreasing serum levels of AST, ALT, total and direct bilirubin when compared to D-Gal-aging group. SFN significantly increased hepatic GSH level as well as catalase and glutathione-S-transferase activities while counteracted the elevation in hepatic oxidative stress markers; MDA, NO and protein carbonyl in aged rats. SFN abrogated the dysregulation in hepatic Keap-1, Nrf-2 and HO-1and limited the elevation of TNF-α and TGF-β concentrations in aging liver. Histopathologically, SFN decreased the intensity of hepatic fibrous proliferation in D-Gal-induced aging. In conclusion, SFN has shown hepatic anti-aging potential through promoting the antioxidant machinery via regulating Keap-1, Nrf-2 and HO-1 and antioxidant enzyme activities as well as ameliorating oxidative stress, hampering the inflammatory cytokines; TNF-ɑ and TGF-β, and limiting hepatic fibrosis in a dose dependent manner.

Keywords: Aging; D-galactose; Fibrosis; Nrf-2; Rats; Sulforaphane.

MeSH terms

  • Aging / metabolism*
  • Animals
  • Antioxidants / metabolism
  • Biomarkers / blood
  • Galactose / adverse effects*
  • Heme Oxygenase (Decyclizing) / metabolism
  • Isothiocyanates / pharmacology*
  • Kelch-Like ECH-Associated Protein 1 / metabolism*
  • Liver / cytology
  • Liver / drug effects*
  • Liver / metabolism*
  • Male
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Wistar
  • Sulfoxides
  • Transforming Growth Factor beta / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antioxidants
  • Biomarkers
  • Isothiocyanates
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat
  • Sulfoxides
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Heme Oxygenase (Decyclizing)
  • Hmox1 protein, rat
  • sulforaphane
  • Galactose