Tocotrienol‐Rich Fraction Ameliorates Antioxidant Defense Mechanisms and Improves Replicative Senescence‐Associated Oxidative Stress in Human Myoblasts

Abstract

During aging, oxidative stress affects the normal function of satellite cells, with consequent regeneration defects that lead to sarcopenia. This study aimed to evaluate tocotrienol-rich fraction (TRF) modulation in reestablishing the oxidative status of myoblasts during replicative senescence and to compare the effects of TRF with other antioxidants (α-tocopherol (ATF) and N-acetyl-cysteine (NAC)). Primary human myoblasts were cultured to young, presenescent, and senescent phases. The cells were treated with antioxidants for 24 h, followed by the assessment of free radical generation, lipid peroxidation, antioxidant enzyme mRNA expression and activities, and the ratio of reduced to oxidized glutathione. Our data showed that replicative senescence increased reactive oxygen species (ROS) generation and lipid peroxidation in myoblasts. Treatment with TRF significantly diminished ROS production and decreased lipid peroxidation in senescent myoblasts. Moreover, the gene expression of superoxide dismutase (SOD2), catalase (CAT), and glutathione peroxidase (GPX1) was modulated by TRF treatment, with increased activity of superoxide dismutase and catalase and reduced glutathione peroxidase in senescent myoblasts. In comparison to ATF and NAC, TRF was more efficient in heightening the antioxidant capacity and reducing free radical insults. These results suggested that TRF is able to ameliorate antioxidant defense mechanisms and improves replicative senescence-associated oxidative stress in myoblasts.

Tocotrienol-Rich Fraction (TRF) Improves the Viability of Wild-Type Saccharomyces cerevisiae in the Initial Stationary Phase

“…A study by Raspor et al, (Raspor et al 2005) demonstrate that treatment with Trolox, (α-tocopherol analogue) increased the cell viability, decreased intracellular ROS formation and suppressed DNA oxidation in Saccharomyces cerevisiae. In a human myoblast cell culture model, TRF treatment reduced the amount of intracellular ROS, reduced lipid peroxidation and decreased the number of cells undergoing late apoptotic events in senescent cells (Khor et al 2017).…”

“…To prevent these damages, there are endogenous and exogenous antioxidants defence system that can eliminate the free radicals. Examples of endogenous antioxidants include the enzymes catalase and glutathione peroxidases which reduce hydrogen peroxide (Khor et al 2017), while the exogenous ones include vitamins C (Aumailley et al 2016) and vitamin E (Zadeh-ardabili et al 2017).…”

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

“…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].…”

Comparing Palm Oil, Tocotrienol-Rich Fraction and α-Tocopherol Supplementation on the Antioxidant Levels of Older Adults

“…The enzymatic components of the antioxidative defense system comprises several antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), enzymes of ascorbate-glutathione (AsA-GSH) cycle, ascorbate peroxidase (APX), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), and glutathione reductase (GR) [ 21 ] as well as non-enzymatic antioxidant systems such as bilirubin, glutathione (GSH), carotenoids, and vitamins C and E. The antioxidant enzymes operate in different subcellular compartments and respond in concert when cells are exposed to oxidative stress [ 22 ]. However, the effectiveness of the natural antioxidant network has been reported to decline with aging [ 23 , 24 , 25 ]. Thus, the purpose of this study is to compare the effects of TRF and α-TF supplementation, respectively, on the antioxidant levels of healthy individuals aged between 50 and 55 years.…”