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Title:	Perubahan gen dan aktiviti enzim berkait usia melalui tapak jalan pengisyaratan Nrf2/ARE oleh piper betle, fraksi kaya tokotrienol dan chlorella vulgaris dalam mencit c57bl/6
Authors:	Nor Syahida Aliahmat (P47781)
Supervisor:	Yasmin Anum Mohd Yusof, Prof. Dr.
Keywords:	Perubahan gen Piper betle Dissertations, Academic -- Malaysia Universiti Kebangsaan Malaysia -- Dissertations
Issue Date:	10-Jul-2014
Description:	Penuaan terjadi apabila berlakunya peningkatan dan pengumpulan spesis oksigen reaktif (ROS) yang membawa kepada kerosakan molekul seterusnya mengakibatkan degenerasi dan disfungsi pada peringkat sel dan tisu. Suplementasi dengan produk semulajadi yang mengandungi antioksidan yang tinggi dapat mengubah perubahan berkait usia. Kajian ini dijalankan bagi mengkaji kesan antioksidan Piper betle (PB), fraksi kaya tokotrienol (TRF) dan Chlorella vulgaris (CV) ke atas modulasi tapak jalan pengisyaratan Nrf2/ARE berkait dengan penghasilan enzim antioksidan (SOD, GPx, CAT) dan enzim fasa II detoksifikasi (HO1 dan NQO1) semasa penuaan mencit. Mencit dibahagikan kepada tiga kumpulan iaitu muda (6 bulan), pertengahan (12 bulan) dan tua (18 bulan). Kemudian, ia dibahagikan kepada dua kumpulan kawalan yang diberi air suling dan minyak zaitun. Kumpulan rawatan terdiri daripada PB (10 mg/kg dan 50 mg/kg), TRF (30 mg/kg) dan CV (50 mg/kg) yang disuplementasi selama 2 bulan. Aktiviti enzim antioksidan, aras MDA dan ekspresi gen dan protein bagi enzim antioksidan dan enzim detoksifikasi fasa II melalui tapak jalan pengisyaratan Nrf2/ARE diukur. Bagi aktiviti enzim antioksidan, PB (10 mg/kg) menurunkan aktiviti CAT dalam semua kumpulan umur, meningkatkan aktiviti GPx dan SOD dalam kumpulan umur pertengahan dan tua berbanding kumpulan kawalan air (p<0.05). Kepekatan PB (50 mg/kg) memberikan keputusan yang sama pada umur pertengahan dan tua di mana ia meningkatkan aktiviti GPx dalam kumpulan umur pertengahan dan meningkatkan aktiviti SOD dan GPx dalam kumpulan umur tua berbanding kumpulan kawalan air (p<0.05). Namun berbeza dengan kepekatan PB rendah (10 mg/kg), kepekatan PB (50 mg/kg) meningkatkan aktiviti CAT dalam kumpulan umur muda (p<0.05). Rawatan TRF menurunkan aktiviti SOD berbanding kumpulan kawalan minyak zaitun pada kumpulan umur pertengahan dan tua (p<0.05). Rawatan CV menurunkan aktiviti CAT dalam kumpulan umur muda dan meningkatkan aktiviti GPx dalam kumpulan umur pertengahan berbanding kumpulan kawalan air (p<0.05). Rawatan PB (10 mg/kg) dan TRF menurunkan aras MDA dalam kumpulan umur pertengahan manakala CV menurunkan aras MDA dalam semua peringkat umur (p<0.05). Dalam ekspresi gen, kajian mendapati PB (10 mg/kg dan 50 mg/kg) meningkatkan gen HO1, NQO1 dan CAT dalam kumpulan umur muda dan meningkatkan gen Nrf2, HO1, NQO1, GPx1 dan CAT dalam kumpulan umur tua (p<0.05). TRF menurunkan gen Keap1 dalam kumpulan umur muda dan meningkatkan gen HO1 dalam kumpulan umur tua (p<0.05). CV menurunkan gen Keap1 dalam kumpulan umur pertengahan dan meningkatkan gen GPx1 dan CAT dalam kumpulan umur tua (p<0.05). PB (10 mg/kg dan 50 mg/kg) menurunkan protein Nrf2 sitoplasma dan meningkatkan protein Nrf2 nukleus dalam semua kumpulan umur (p<0.05). Walau bagaimanapun, TRF dan CV gagal menunjukkan penemuan yang sama. PB meningkatkan ekspresi protein CAT dalam kumpulan umur muda dan protein NQO1 dan CAT dalam kumpulan umur pertengahan serta umur tua (p<0.05). Kesimpulannya, PB mengaruh gen dan protein perlindungan sel melalui tapak jalan pengisyaratan Nrf2/ARE lebih baik daripada TRF dan CV terutama dalam kumpulan umur tua. Di samping itu, rawatan PB, TRF dan CV mampu memodulasikan perubahan berkait usia dalam aktiviti-aktiviti enzim antioksidan pada eritrosit.,Aging occurs when there is an increase and accumulation of reactive oxygen species (ROS) leading to molecular damage resulting in degeneration and dysfunction at the cellular and tissue level. Supplementation of natural product with high antioxidant capacity can alter the age related changes. This study was conducted to investigate the effects of antioxidants Piper betle (PB), Tocotrienol Rich Fraction (TRF) and Chlorella vulgaris (CV) on modulating the Nrf2/ARE signalling pathway associated with the production of endogenous antioxidants (SOD, GPx, CAT) and phase II detoxifying enzymes (HO1 and NQO1) during ageing in mice. The mice were divided into three groups: young (6 months old), middle (12 months old) and old age (18 months old). The mice were sub-divided into two control groups given distilled H2O and olive oil. Treatment groups consisted of PB (10 mg/kg and 50 mg/kg), TRF (30 mg/kg) and CV (50 mg/kg) supplemented for 2 months. Antioxidant enzymes activities, MDA levels and genes and proteins expression of antioxidants and phase II detoxifying enzymes via Nrf2/ARE signalling pathway were determined. For antioxidant enzyme activities, PB (10 mg/kg) decreased CAT activity in all age groups, increased GPx and SOD activities in middle and old age groups compared to dH2O control group (p<0.05). Higher concentration of PB (50 mg/kg) gave similar results for middle and old age groups, whereby it increased GPx activity in middle age and increased SOD and GPx activities in old age groups compared with dH2O control group (p<0.05). However, in contrast to low PB concentration (10 mg/kg), higher concentration of PB increased CAT activity in young age group (p<0.05). TRF treatment decreased SOD activity compared to the control olive oil group in middle and old age groups (p<0.05). CV treatment decreased CAT activity in young age and increased GPx activity in middle age groups compared to the control group (p<0.05). PB (10 mg/kg) and TRF treatment decreased blood MDA levels only in the middle age group while CV decreased blood MDA levels in all age groups (p<0.05). For genes and proteins expression, PB at both concentrations (10 mg/kg and 50 mg/kg) upregulated HO1, NQO1 and CAT genes in young age group and upregulated Nrf2, HO1, NQO1, GPx1 and CAT genes in old age group (p<0.05). TRF downregulated Keap1 gene in young age group and upregulated HO1 gene in old age group (p<0.05). CV downregulated Keap1 gene in middle age group and upregulated GPx1 and CAT genes in old age group (p<0.05). PB (10 mg/kg and 50 mg/kg) was shown to downregulate cytoplasmic Nrf2 protein and upregulate the nuclear Nrf2 protein in all age groups (p <0.05). However, TRF and CV failed to show similar finding. PB increased the expressions of CAT protein in young age group and NQO1 and CAT proteins in the middle and old age groups (p<0.05). In conclusion, PB induced the cytoprotective genes through the Nrf2/ARE signaling pathway better than TRF and CV especially in old age group. PB, TRF and CV treatments were also capable of modulating age-related changes in erythrocyte antioxidant enzyme activities.,Sarjana Sains Perubatan
Pages:	197
Publisher:	UKM, Kuala Lumpur
Appears in Collections:	Faculty of Medicine / Fakulti Perubatan

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