L-carnitine attenuates oxidant injury in HK-2 cells via ROS-mitochondria pathway.
Oxidative stress has been considered as the possible mechanism of renal ischemia/reperfusion injury. L-carnitine is an endogenous mitochondrial membrane compound and could effectively protect ischemia-reperfusion injury in the kidney. To elucidate the nephroprotective effects of L-carnitine, here we assessed the effect of L-carnitine on hydrogen peroxide (H(2)O(2))-mediated oxidative stress in the human proximal tubule epithelial cell line, HK-2 cells. The results showed that pretreatment with L-carnitine 12h inhibited H(2)O(2)-induced cell viability loss, intracellular reactive oxygen species generation and lipid peroxidation in a concentration-dependent manner. Also L-carnitine promoted endogenous antioxidant defense components including total antioxidative capacity, glutathione peroxidase, catalase and superoxide dismutase. In parallel, cell apoptosis triggered by H(2)O(2) characterized with the DNA fragment and caspase-3 activity were also inhibited by L-carnitine. Furthermore, mitochondrial dysfunction associated with cell apoptosis including membrane potential loss, down-regulation of Bcl-2 and up-regulation of Bax and the release of cytochrome c were abrogated in the presence of L-carnitine. These results suggested that L-carnitine could protect HK-2 cells from H(2)O(2)-induced injury through the inhibition of oxidative damage, mitochondria dysfunction and ultimately inhibition of cell apoptosis, which indicates that L-carnitine may be a promising approach for the treatment of oxidative stress in renal diseases.
Ye
Junsheng
J
Department of Organ Transplantation, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Li
Juan
J
Yu
Yuming
Y
Wei
Qiang
Q
Deng
Wenfeng
W
Yu
Lixin
L
D015153:Blotting, Western; D002331:Carnitine / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*
D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D053148:Caspase 3; D002331:Carnitine