Sains Malaysiana 45(9)(2016): 1363–1370

Tocotrienol-Rich Fraction Supplementation Modulates Antioxidant Enzymes Activity and Reduces DNA Damage in APPswe/PS1dE9 Alzheimer’s Disease Mouse Model

(Suplementasi Fraksi Kaya Tokotrienol Memodulasi Aktiviti Enzim Antioksidan dan Mengurangkan Kerosakan DNA pada APPswe/PS1dE9 Model Mencit Penyakit Alzheimer)

H.A. DAMANHURI^1,2*, N.I. ABDUL RAHIM¹, W.N.W. NASR1^I, J.K. TAN¹, S. MAKPOL¹,

M. MAZLAN³, I. TOOYAMA⁴ & W.Z. WAN NGAH^1,2

¹Biochemistry Department, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaakob Latif, 56000 Cheras, Kuala Lumpur, Federal Territory, Malaysia

²UKM Medical Molecular Biology Institute, Jalan Yaakob Latif, 56000 Cheras, Kuala Lumpur, Federal Territory, Malaysia

³Faculty of Medicine, Universiti Teknologi MARA, Jalan Hospital, 47000 Sungai Buloh, Selangor Darul Ehsan, Malaysia

⁴Molecular Neuroscience Research Centre, Shiga University of Medical Sciences, Seta Tsukinowacho, Otsu 520-2192, Shiga, Japan

Received: 21 December 2015/Accepted: 29 April 2016

ABSTRACT

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by deterioration of the brain functions that result in impairment of memory, cognition and behavioural functions. Oxidative stress is well known to be one of the causative factors for AD. Thus this disease is potentially modulated by natural antioxidants such as vitamin E. The aim of this study was to evaluate the effect of tocotrienol-rich fraction (TRF) supplementation on antioxidant enzymes and DNA damage using APPswe/PS1dE9 transgenic mouse model of AD. Animals were supplemented with TRF (200 mg/kg) or alpha-tocopherol (αT) (200 mg/kg) for six months starting from nine months old. We found that superoxide dismutase (SOD) activity in AD mouse was decreased by supplementation of TRF and αT as compared with AD control mouse with no significant differences in glutathione peroxidise (GPx) activity in all groups. TRF supplementation significantly increased catalase (CAT) activity. The level of DNA damage of AD mouse shows significant decrease with supplementation of TRF and αT. In conclusion, TRF was able to modulate antioxidant enzymes activity and decreased the level of DNA damage of AD transgenic mouse model.

Keywords: Alzheimer’s disease; oxidative status; tocotrienol-rich fraction

ABSTRAK

Penyakit Alzheimer (AD) adalah gangguan progresif neurodegeneratif yang boleh dicirikan dengan kemerosotan fungsi otak yang mengakibatkan kerosakan ingatan, kognitif dan fungsi tingkah laku. Tekanan oksidatif terkenal sebagai salah satu faktor penyebab AD. Oleh itu penyakit ini berpotensi dimodulasikan oleh antioksidan semula jadi seperti vitamin E. Kajian ini bertujuan menilai kesan suplementasi fraksi kaya tokotrienol (TRF) ke atas enzim antioksidan dan kerosakan DNA menggunakan APPswe/PS1dE9 model mencit transgenik AD. Model haiwan ini telah diberi suplementasi TRF (200 mg/kg) atau αT (200 mg/kg) selama enam bulan dari usia sembilan bulan. Keputusan menunjukkan aktiviti SOD menurun pada mencit AD yang telah disuplementasi dengan TRF dan αT berbanding dengan mencit AD kawalan. Tiada perbezaan signifikan dalam aktiviti GPx dalam semua kumpulan. Manakala mencit AD yang diberi suplementasi TRF menunjukkan peningkatan ketara dalam aktiviti CAT. Daripada segi kerosakan DNA, suplementasi TRF dan αT menunjukkan penurunan ketara pada mencit AD. Kesimpulannya, TRF berpotensi untuk memodulasi aktiviti enzim antioksidan dan mengurangkan tahap kerosakan DNA model mencit transgenik AD.

Kata kunci: Fraksi kaya tokotrienol; penyakit Alzheimer; status oksidatif

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*Corresponding author; email: hanafi.damanhuri@ppukm.ukm.edu.my