L-carnitine improves oxidative stress and suppressed energy metabolism but not renal dysfunction following release of acute unilateral ureteral obstruction in rat.

BACKGROUND AND AIM: We recently showed that L-carnitine reduced oxidative stress and suppressed energy metabolism, while α-tocopherol only prevented redox imbalance, in the obstructed kidney of rats subjected to 24-hr of unilateral ureteral obstruction (UUO). The present study was undertaken to investigate the effects of both compounds on disturbed renal hemodynamics, solutes-excretion, and urine-concentrating ability as well as renal oxidative stress and suppressed metabolism at early hours following release of 24-hr UUO. METHODS: UUO was induced in anaesthetized rats that received L-carnitine, α-tocopherol or their vehicles in four different groups. Each rat was re-anaesthetized, prepared for renal functional measurements, and its ureteral obstruction was released at 24-hr. Then, urines of both kidneys were separately collected during 30-90 min of post-release, with taking blood samples at beginning and end of it. Finally, both kidneys were removed and preserved at -80°C for future measuring their levels of ATP and ADP as well as malondialdehyde (MDA) and ferric reducing/antioxidant power (FRAP). There were also sham and control groups. RESULTS: Post-obstructed kidney (POK) of vehicle-treated groups compared to equivalent kidney of sham group had lower ATP, ATP/ADP, FRAP, creatinine clearance, absolute Na(+)- and K(+)-excretion, and effective free-water reabsorption, but higher MDA and ADP. L-carnitine could improve oxidative stress and suppressed energy metabolism and α-tocopherol normalized redox state, but both compounds did not have any effects on altered functional variables of the POK. CONCLUSION: Oxidative stress and suppressed energy metabolism may not be involved in the development of renal dysfunction during acute ureteral obstruction.

Comparison of the effects of L: -carnitine and alpha-tocopherol on acute ureteral obstruction-induced renal oxidative imbalance and altered energy metabolism in rats.

The suppression of renal energy metabolism during ureteral obstruction is a well-known phenomenon; however, its exact responsible mechanism(s) and association with simultaneously induced renal oxidative stress have not been clarified. This study examined the improving effects of L: -carnitine, a facilitating cofactor for mitochondrial oxidation of fatty-acids as well as a scavenger of free-radicals, and alpha-tocopherol as the most potent antioxidant on renal metabolic defect and oxidative stress induced by acute unilateral ureteral obstruction (UUO). The left ureter was ligated in ether-anaesthetised rats, in which L: -carnitine, alpha-tocopherol or their vehicles were intraperitoneally injected in four different groups. After elapsing 24 h of UUO-induction, both kidneys were removed and stored at -80 degrees C. There were also two sham-operated and control groups. The kidney samples were assessed to measure the levels of ferric reducing/antioxidant power (FRAP) and malondialdehyde (MDA) for evaluating their redox state, as well as, their amounts of adenosine triphosphate (ATP) and adenosine diphosphate (ADP) by using luciferin-luciferase method. As much as 24 h of UUO in vehicle-treated groups caused increases in MDA and ADP, but decreases in FRAP, ATP, and ATP/ADP of the obstructed kidney with respect to those of the sham group. alpha-tocopherol normalised the levels of MDA and FRAP but did not affect the altered amounts of energy metabolic indices in the obstructed kidney, while L: -carnitine could ameliorate all of them. These findings suggest that oxidative stress may not involve in development of acute UUO-induced suppression of renal aerobic metabolism, and probably reduction of energy substrates is a responsible factor.