Saleh D.O.Mansour D.F.Hashad I.M.Bakeer R.M.Department of PharmacologyMedical Research DivisionThe National Research Centre33 EL Bohouth St. (former EL Tahrir St.)P.O. 12622DokkiGizaEgypt; Department of Clinical Pharmacy and Pharmacy PracticeFaculty of PharmacyAhram Canadian UniversityEgypt; Clinical Biochemistry UnitFaculty of Pharmacy and BiotechnologyGerman University in CairoCairoEgypt; Department of PathologyFaculty of MedicineHelwan UniversityEgypt; Instructor of PathologyOctober University of Modern Sciences and Arts (MSA)UniversityEgypt2020-01-092020-01-092019142999https://doi.org/10.1016/j.ejphar.2019.04.043PubMed ID 31039346https://t.ly/zN5rNScopusAging; 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.EnglishAgingD-galactoseFibrosisNrf-2RatsSulforaphanealanine aminotransferaseaspartate aminotransferasebilirubincatalasegalactoseglutathioneglutathione transferaseheme oxygenase 1kelch like ECH associated protein 1malonaldehydenitric oxidesulforaphanetranscription factor Nrf2transforming growth factor betatumor necrosis factorantioxidantbiological markergalactoseheme oxygenaseHmox1 protein, ratisothiocyanic acid derivativekelch like ECH associated protein 1Nfe2l2 protein, ratsulforafantranscription factor Nrf2transforming growth factor betatumor necrosis factoradultagingalanine aminotransferase blood levelanimal tissueantiaging activityantioxidant activityArticleaspartate aminotransferase blood levelbilirubin blood levelcell proliferationcontrolled studydose responsedrug effectdrug efficacydrug mechanismenzyme activityhistopathologyliverliver protectionmalenonhumanoxidative stresspriority journalratsignal transductionaginganimalbloodcytologydrug effectlivermetabolismWistar ratAgingAnimalsAntioxidantsBiomarkersGalactoseHeme Oxygenase (Decyclizing)IsothiocyanatesKelch-Like ECH-Associated Protein 1LiverMaleNF-E2-Related Factor 2Oxidative StressRatsRats, WistarTransforming Growth Factor betaTumor Necrosis Factor-alphaArticlehttps://doi.org/10.1016/j.ejphar.2019.04.043PubMed ID 31039346