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

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Date

2019

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Volume Title

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Article

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Elsevier B.V.

Series Info

European Journal of Pharmacology
855

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-? and TGF-? 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-? and TGF-?, and limiting hepatic fibrosis in a dose dependent manner. � 2019 Elsevier B.V.

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Scopus

Keywords

Aging, D-galactose, Fibrosis, Nrf-2, Rats, Sulforaphane, alanine aminotransferase, aspartate aminotransferase, bilirubin, catalase, galactose, glutathione, glutathione transferase, heme oxygenase 1, kelch like ECH associated protein 1, malonaldehyde, nitric oxide, sulforaphane, transcription factor Nrf2, transforming growth factor beta, tumor necrosis factor, antioxidant, biological marker, galactose, heme oxygenase, Hmox1 protein, rat, isothiocyanic acid derivative, kelch like ECH associated protein 1, Nfe2l2 protein, rat, sulforafan, transcription factor Nrf2, transforming growth factor beta, tumor necrosis factor, adult, aging, alanine aminotransferase blood level, animal tissue, antiaging activity, antioxidant activity, Article, aspartate aminotransferase blood level, bilirubin blood level, cell proliferation, controlled study, dose response, drug effect, drug efficacy, drug mechanism, enzyme activity, histopathology, liver, liver protection, male, nonhuman, oxidative stress, priority journal, rat, signal transduction, aging, animal, blood, cytology, drug effect, liver, metabolism, Wistar rat, Aging, Animals, Antioxidants, Biomarkers, Galactose, Heme Oxygenase (Decyclizing), Isothiocyanates, Kelch-Like ECH-Associated Protein 1, Liver, Male, NF-E2-Related Factor 2, Oxidative Stress, Rats, Rats, Wistar, Transforming Growth Factor beta, Tumor Necrosis Factor-alpha

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