Effects of Aging and Tocotrienol‐Rich Fraction Supplementation on Brain Arginine Metabolism in Rats

Abstract

Accumulating evidence suggests that altered arginine metabolism is involved in the aging and neurodegenerative processes. This study sought to determine the effects of age and vitamin E supplementation in the form of tocotrienol-rich fraction (TRF) on brain arginine metabolism. Male Wistar rats at ages of 3 and 21 months were supplemented with TRF orally for 3 months prior to the dissection of tissue from five brain regions. The tissue concentrations of L-arginine and its nine downstream metabolites were quantified using high-performance liquid chromatography and liquid chromatography tandem mass spectrometry. We found age-related alterations in L-arginine metabolites in the chemical- and region-specific manners. Moreover, TRF supplementation reversed age-associated changes in arginine metabolites in the entorhinal cortex and cerebellum. Multiple regression analysis revealed a number of significant neurochemical-behavioral correlations, indicating the beneficial effects of TRF supplementation on memory and motor function.

Evaluation of Varied Modalities of Tocotrienol Supplementations to Counter the Cerebellar Oxidative Stress Caused by Low-to-moderate Doses of Ethanol in Rats

“…Maintenance of systemic, organ or regional GSH level by vitamin E, TRF or T3 in presence of oxidative stressor had been reported times and again. [23,32,[37][38][39][40][41][42] Increases in cerebellar GSH level were noticed in the ST3 group (statistically significant) and TT3 group (statistically significant) in comparison to NT3 and PT3 groups of Et-0 phase of current study. However, in presence of Et exposures, TT3 group abled to maintain the level of cerebellar GSH while ST3 group failed to do so.…”

Oxidative Changes and Cognitive Function Decline in Aging Rats

“…Taridi et al [28] showed that TRF supplementation to aging rats reduced markedly level of anxiety, improved spatial learning and memory, reduced amount and severity of DNA damage, reduced level of MDA, and increased levels of antioxidant enzyme activity and plasma/ brain Vitamin E compared with age-matched controls. In another study, TRF supplementation reversed age-associated changes in arginine metabolites in the entorhinal cortex and cerebellum of rats [34].…”

Modulation of Proteome Profile in AβPP/PS1 Mice Hippocampus, Medial Prefrontal Cortex, and Striatum by Palm Oil Derived Tocotrienol-Rich Fraction

“…In addition, ␣-tocotrienol has been shown to protect neuronal cell from glutamate-induced toxicity primarily by a direct antioxidant action [70]. In an in vivo study, three months supplementation of TRF (200 mg/kg) has been reported to markedly reduce lipid peroxidation, modulate antioxidant enzymes activity and brain arginine metabolism, and also improve memory in aged rats [19,71]. Tocotrienols supplementation has also been reported to improve lipid profiles in chronic hemodialysis patients [72].…”

“…Tocotrienol-rich fraction (TRF), a mixture of vitamin E analogs derived from palm oil, has garnered attention recently. Several reports have shown the potential of TRF in modulating A␤ metabolism [17], brain metabolites [18,19], antioxidant defense mechanisms [19,20], and cancer prevention [21]. Previously we have demonstrated that long-term supplementation (ten months) of TRF on APPswe/PS1dE9 double transgenic (Tg) mice (A␤PP/PS1), a mouse model of AD, reduced amyloid pathology in the brain [17].…”