Ischemia-induced
mitochondrial dysfunction and
ATP depletion in the kidney result in disruption of primary functions and acute injury of the kidney. This study tested whether γ-
tocotrienol (GTT), a member of the
vitamin E family, protects mitochondrial function, reduces
ATP deficits, and improves renal functions and survival after
ischemia/reperfusion injury. Vehicle or GTT (200 mg/kg) were administered to mice 12 h before bilateral kidney
ischemia, and endpoints were assessed at different timepoints of reperfusion. GTT treatment reduced decreases in state 3 respiration and accelerated recovery of this function after
ischemia. GTT prevented decreases in activities of complexes I and III of the respiratory chain, and blocked
ischemia-induced decreases in F0F1-ATPase activity and
ATP content in renal cortical tissue. GTT improved renal morphology at 72 h after
ischemia, reduced numbers of necrotic proximal tubular and inflammatory cells, and enhanced tubular regeneration. GTT treatment ameliorated increases in plasma
creatinine levels and accelerated recovery of
creatinine levels after
ischemia. Lastly, 89% of mice receiving GTT and 70% of those receiving vehicle survived
ischemia. Conclusions: Our data show novel observations that GTT administration improves mitochondrial respiration, prevents
ATP deficits, promotes tubular regeneration, ameliorates decreases in renal functions, and increases survival after
acute kidney injury in mice.