Gamma Tocotrienol and Liver Protection
Oxidative stress is a major mechanism of a variety of renal diseases. Tocopherols and tocotrienols are well known antioxidants. This study aimed to determine if γ-tocotrienol (GT3) protects against mitochondrial dysfunction and renal proximal tubular cell (RPTC) injury caused by oxidant. Primary cultures of RPTC were injured using tert-butyl hydroperoxide (TBHP) in the absence and presence of GT3 or α-tocopherol (AT). ROS production increased 300% in TBHP-injured RPTC. State 3 respiration, oligomycin-sensitive respiration and respiratory control ratio (RCR) decreased 50%, 63%, and 47%, respectively. The number of RPTC with polarized mitochondria decreased 54%. F(0)F(1)-ATPase activity and ATP content decreased 31% and 65%, respectively. Cell lysis increased from 3% in controls to 26% and 52% at 4h and 24h, respectively, after TBHP exposure. GT3 blocked ROS production, ameliorated decreases in state 3 and oligomycin-sensitive respirations and F(0)F(1)-ATPase activity, and maintained RCR and ΔΨ(m) in injured RPTC. GT3 maintained ATP content, blocked RPTC lysis at 4h, and reduced it to 13% at 24h after injury. Treatment with equivalent concentrations of AT did not block ROS production and cell lysis and moderately improved mitochondrial respiration and coupling. This is the first report demonstrating the protective effects of GT3 against RPTC injury by: 1) decreasing production of ROS, 2) improving mitochondrial respiration, coupling, ΔΨ(m), and F(0)F(1)-ATPase function, 3) maintaining ATP levels, and 4) preventing RPTC lysis. Our data suggest that GT3 is superior to AT in protecting RPTC against oxidant injury and may prove therapeutically valuable to prevent renal injury associated with oxidative stress.
Nowak G, Bakajsova D, Hayes C, Hauer-Jensen M, Compadre CM.
γ-Tocotrienol Protects Against Mitochondrial Dysfunction and Renal Cell Death.
J Pharmacol Exp Ther.
University of Arkansas for Medical Sciences.