Inflammation and carnitine in hemodialysis patients.
The bioincompatibility of dialytic systems along with the loss of antioxidant substances via the dialysis may contribute to peripheral blood mononuclear cell (PBMC) activation and the production of inflammatory mediators, such as cytokines, oxygen radicals, and complement fragments, that may sustain a state of chronic microinflammation responsible for the pathogenesis of a variety of diseases, including atherosclerosis, anemia, and malnutrition. Moreover, during hemodialysis (HD), oxidative stress may influence several intracellular signaling enzymes, including some stress-activated kinases, such as jun-N-terminal kinase (JNK), potentially leading to PBMC activation and proinflammatory cytokine production. Recent reports suggest that L-carnitine may play an important role in balancing antioxidative systems. Therefore, we sought to evaluate the effect of L-carnitine supplementation on the PBMC responses to oxidative stress induced by different HD membranes. We observed in PBMC from cellulosic (C)-treated patients an increase in the amount of intracellular tyrosine-phosphorylated proteins and a striking activation of JNK, as compared with synthetic (S)-treated patients. On the contrary, 3 months of L-carnitine supplementation significantly lowered intracellular levels of phosphorylated proteins and JNK activity in PBMC from C-treated patients. In addition, after 180 minutes of HD, a significant decrease in global plasma antioxidant capacity was found, particularly in C-treated patients, whereas L-carnitine supplementation improved plasma antioxidant capacity levels in these patients. These observations were also confirmed by in vitro experiments, showing the ability of L-carnitine to reduce the JNK activation in normal PBMC exposed to different amounts of hydrogen peroxide. In conclusion, the uremic milieu is characterized by an enhanced inflammatory response and an increased oxidant load, affecting lipids, carbohydrates, and proteins. Regular L-carnitine supplementation in HD patients can improve cellular defense against chronic inflammation and oxidative stress, most likely by modulating the specific signal transduction cascade activated by an overproduction of proinflammatory cytokines and oxidative stress.
Pertosa
Giovanni
G
Division of Nephrology, Dialysis and Transplantation, Department of Emergency and Transplantation, University of Bari, Bari, Italy. g.pertosa@nephro.uniba.it <g.pertosa@nephro.uniba.it>
Grandaliano
Giuseppe
G
Simone
Simona
S
Soccio
Michela
M
Schena
Francesco Paolo
FP
D050197:Atherosclerosis / Q000209:etiology; D002331:Carnitine / Q000008:administration & dosage / Q000502:physiology*; D018932:Chemokine CCL2 / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D015850:Interleukin-6 / Q000502:physiology; D048031:JNK Mitogen-Activated Protein Kinases / Q000097:blood; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000628:therapy; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000201:enzymology / Q000502:physiology; D010750:Phosphoproteins / Q000097:blood; D019000:Phosphotyrosine / Q000097:blood; D006435:Renal Dialysis / Q000009:adverse effects*; D015398:Signal Transduction
D018932:Chemokine CCL2; D015850:Interleukin-6; D010750:Phosphoproteins; D019000:Phosphotyrosine; D048031:JNK Mitogen-Activated Protein Kinases; D002331:Carnitine