Effects of sulforaphane on D-galactose-induced liver aging in rats: Role of keap-1/nrf-2 pathway.
Saleh D.O.; Mansour D.F.; Hashad I.M.; Bakeer R.M.
Date issued:
2019
Publisher:
Elsevier B.V.
Series Info:
European Journal of Pharmacology
855
Type:
Article
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
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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