Sains Malaysiana 51(1)(2022): 249-259

http://doi.org/10.17576/jsm-2022-5101-20

Effects of Age and Tocotrienol-Rich Fraction on Mitochondrial Respiratory Complexes in the Hippocampus of Rats

(Kesan Umur dan Fraksi Kaya Tokotrienol pada Kompleks Respirasi Mitokondria dalam Hipokampus Tikus)

JEN KIT TAN*, SAKINAH HUSNA ABDUL RAZAK, NAZIRAH AB RANI, NUR HALEEDA HAKIMI, HANAFI AHMAD DAMANHURI, SUZANA MAKPOL & WAN ZURINAH WAN NGAH

Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000 Cheras, Kuala Lumpur, Federal Territory, Malaysia

Received: 5 October 2020/Accepted: 19 April 2021

ABSTRACT

Mitochondrial dysfunction is common in the brain with age. Prevention of mitochondrial dysfunction at an early age may protect the brain against neurodegeneration in later life. Tocotrienol-rich fraction (TRF) has been reported to be neuroprotective in old rats, but its effect remains unknown for middle-aged animals. This study aimed to determine the effect of TRF on activities of mitochondrial respiratory chain complexes in the hippocampus of middle-aged rats. Male Sprague Dawley rats were divided into 4 groups: young control (3 months old), adult control (12 months old), adult rats supplemented with palm kernel oil (PKO) as the vehicle, and adult rats supplemented with TRF by gavage at 200 mg/kg body weight/day for 3 months. At the end of the supplementation, activities of complex I, I+III, II, II+III, III, IV, and citrate synthase in the isolated mitochondria of the hippocampus were measured by spectrophotometry. Complex II activity was higher, while citrate synthase activity was lower in adult rats than in young rats. A decrease of citrate synthase activity suggests loss of mitochondrial mass and intactness in the hippocampus at middle age. Interestingly, PKO-treated adult rats had lower complex I and IV activities, but higher complex I+III activity than adult control rats. These findings indicate PKO modulated activities of the complexes. In TRF-treated adult rats, the complex I activity was higher, while the complex IV activity was lower than PKO-treated adult rats. TRF restored the complex I activity and may have the potential to reverse complex I deficiency.

Keywords: Aging; brain; mitochondria; respiratory complex; tocotrienols

ABSTRAK

Mitokondria disfungsi dalam otak biasanya berlaku pada usia tua. Halangan terhadap disfungsi tersebut pada waktu muda mungkin berupaya melindungi otak daripada neurodegenerasi semasa berusia. Fraksi kaya tokotrienol (TRF) dilaporkan bersifat pelindung neuron pada tikus tua, namun kesan tersebut tidak diketahui pada haiwan yang berumur pertengahan. Kajian ini bertujuan untuk menentukan kesan TRF terhadap aktiviti kompleks rantaian respiratori mitokondria dalam hipokampus tikus berumur pertengahan. Tikus jantan Sprague Dawley dibahagikan kepada 4 kumpulan: kawalan muda (berusia 3 bulan), kawalan dewasa (berusia 12 bulan), tikus dewasa dengan suplementasi minyak isirung sawit (PKO) sebagai pembawa dan tikus dewasa dengan suplementasi TRF (200 mg/kg) melalui gavaj untuk 3 bulan. Pada hujung suplementasi, aktiviti kompleks I, I+III, II, II+III, III, IV dan sitrat sintase dalam mitokondria yang diasingkan daripada hipokampus diukur dengan spektrofotometri. Aktiviti kompleks II adalah lebih tinggi, manakala sitrat sintase adalah lebih rendah pada tikus dewasa berbanding dengan yang muda. Penurunan aktiviti sitrat sintase mencadangkan kehilangan bilangan dan keutuhan mitokondria dalam hipokampus pada umur pertengahan. Kumpulan PKO mempunyai aktiviti kompleks I dan IV yang lebih rendah, manakala aktiviti kompleks I+III yang lebih tinggi berbanding dengan kawalan tikus dewasa. Hasil ini menunjukkan bahawa PKO mengawal atur aktiviti kompleks tersebut. Dalam kumpulan TRF, aktiviti kompleks I adalah lebih tinggi, manakala aktiviti kompleks IV adalah lebih rendah berbanding dengan kumpulan PKO. TRF telah memulihkan aktiviti kompleks I dan berpotensi menghalang keadaan yang disebabkan oleh defisiensi kompleks I.

Kata kunci: Kompleks respirasi; mitokondria; otak; penuaan; tokotrienol

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*Corresponding author; email: jenkittan@ukm.edu.my