Ploumis Pasadakis

Effects of L-carnitine on oxidative stress responses in patients with renal disease.

PURPOSE Hemodialyzed patients demonstrate elevated oxidative stress and reduced functional status. Exercise induces health benefits, but acute exertion up-regulates oxidative stress responses in patients undergoing hemodialysis. Therefore, the aim of the present study was to examine the effect of L-carnitine supplementation on i) exercise performance and ii) blood redox status both at rest and after exercise. METHODS Twelve hemodialysis patients received either L-carnitine (20 mg kg(-1) i.v.) or placebo in a double-blind, placebo-controlled, counterbalanced, and crossover design for 8 wk. Participants performed an exercise test to exhaustion before and after supplementation. During the test, V˙O2, respiratory quotient, heart rate, and time to exhaustion were monitored. Blood samples, collected before and after exercise, were analyzed for lactate, malondialdehyde, protein carbonyls, reduced and oxidized glutathione, antioxidant capacity, catalase, and glutathione peroxidase activity. RESULTS Blood carnitine increased by L-carnitine supplementation proportionately at rest and after exercise. L-carnitine supplementation increased time to fatigue (22%) and decreased postexercise lactate (37%), submaximal heart rate, and respiratory quotient but did not affect V˙O2peak. L-carnitine supplementation increased reduced/oxidized glutathione (2.7-fold at rest, 4-fold postexercise) and glutathione peroxidase activity (4.5% at rest, 10% postexercise) and decreased malondialdehyde (19% at rest and postexercise) and protein carbonyl (27% at rest, 40% postexercise) concentration. CONCLUSIONS Data suggest that a 2-month L-carnitine supplementation may be effective in attenuating oxidative stress responses, enhancing antioxidant status, and improving performance of patients with end-stage renal disease.

Acute exercise may exacerbate oxidative stress response in hemodialysis patients.

Background/Aims: Hemodialyzed patients (HD) demonstrate elevated oxidative stress (OXS) levels. Exercise effects on OXS response and antioxidant status of HD was investigated in the present study. Methods: Twelve HD and 12 healthy controls (HC) performed a graded exercise protocol. Blood samples, collected prior to and following exercise, were analyzed for lactate, thiobarbituric acid-reactive substances (TBARS), protein carbonyls (PC), reduced (GSH) and oxidized glutathione (GSSG), total antioxidant capacity (TAC), catalase, and glutathione peroxidase (GPX) activity. Results: HC demonstrated higher time-to-exhaustion (41%), lactate (41%) and VO2 peak (55%) levels. At rest, HD exhibited higher TBARS, PC, and catalase activity values and lower GSH, GSH/GSSG, TAC, and GPX levels. Although exercise elicited a marked change of OXS markers in both groups, these changes were more pronounced (p < 0.05) in HD patients. After adjusting for VO2 peak, differences between groups disappeared. VO2 peakwas highly correlated with GSH/GSSG, TBARS, TAC and PC at rest and after exercise. Conclusions: These results imply that HD demonstrate higher OXS levels and a lower antioxidant status than HC at rest and following exercise. Acute exercise appears to exacerbate OXS response in hemodialyzed patients probably due to diminished antioxidant defense. However, aerobic capacity level seems to be related to OXS responses in this population.

Effect of a Calcium Antagonist (Verapamil) in the Permeability of the Peritoneal Membrane in Patients on Continuous Ambulatory Peritoneal Dialysis

Peritoneal clearances of small solutes, mass transfer, ultrafiltration, and the mass transfer area coefficient were measured in order to evaluate the effect of calcium antagonists on the permeability of the peritoneal membrane in patients on continuous ambulatory peritoneal dialysis. We studied 10 patients before and after the instillation of 10 mg (5 mg/l) of verapamil into the peritoneal cavity. Our results showed a significant increase of urea, creatinine, and uric acid clearances. A significant increase in ultrafiltration and mass transfer coefficient area was also observed (p less than 0.05), while the mass transfer of K+, Na+, and Ca2+ was essentially unchanged. These findings indicate that the intraperitoneal use of verapamil may induce an increase in the peritoneal permeability in patients on continuous ambulatory peritoneal dialysis.

Assessment of association between lipoxygenase genes variants in elderly Greek population and type 2 diabetes mellitus

Background: Inflammation plays a pivotal role in the pathogenesis of diabetes and its complications. Arachidonic acid lipoxygenases have been intensively studied in their role in inflammation in metabolic pathways. Thus, we aimed to explore variants of lipoxygenase genes (arachidonate lipoxygenase genes) in a diabetes adult population using a case-control study design. Methods: Study population consisted of 1285 elderly participants, 716 of whom had type 2 diabetes mellitus. The control group consisted of non-diabetes individuals with no history of diabetes history and with a glycated haemoglobin <6.5% (<48 mmol/mol)] and fasting plasma glucose levels <126 mg/dL. Blood samples were genotyped on Illumina Infinium PsychArray. Variants of ALOX5, ALOX5AP, ALOX12, ALOX15 were selected. All statistical analyses were undertaken within PLINK and SPSS packages utilising permutation analysis tests. Results: Our findings showed an association of rs9669952 (odds ratio = 0.738, p = 0.013) and rs1132340 (odds ratio = 0.652, p = 0.008) in ALOX5AP and rs11239524 in ALOX5 gene with disease (odds ratio = 0.808, p = 0.038). Rs9315029 which is located near arachidonate ALOX5AP also associated with type 2 diabetes mellitus (p = 0.025). No variant of ALOX12 and ALOX15 genes associated with disease. Conclusion: These results indicate a potential protective role of ALOX5AP and 5-arachidonate lipoxygenase gene in diabetes pathogenesis, indicating further the importance of the relationship between diabetes and inflammation. Larger population studies are required to replicate our findings.

Role of eicosanoids of the contralateral kidney in maintenance of two-kidney, one-clip renovascular hypertension in rats.

Objective. To elucidate the role of the eicosanoids prostaglandin E2 (PGE2), 6-keto-prostaglandin F1a (PGF1a) and thromboxane B2 (TXB2) in the maintenance of two-kidney, one-clip renovascular hypertension in rats. Material and methods. The right renal artery was constricted by a silver clip in 63 male Sprague–Dawley rats to induce hypertension, while a sham operation was performed in 17 control rats. Six months after the induction of hypertension, nephrectomy of the clipped kidney was performed. Nephrectomy was followed by a period of high sodium intake. Blood pressure and eicosanoid excretion were measured before and after nephrectomy of the clipped kidney, as well as during high sodium intake. Results. During the chronic phase of Goldblatt hypertension, the amount of vasoconstrictive TXB2 excreted by the contralateral kidney increased compared to that in the controls, whereas PGE2 excretion was unaffected. Eicosanoid excretion before and after removal of the clipped kidney did not differ between post-Goldblatt hypertensive and post-Goldblatt normotensive animals. During the period of high sodium intake, PGE2 excretion increased only in control rats, being unaltered in Goldblatt hypertensive rats. Conclusions. In the chronic phase of two-kidney, one-clip renovascular hypertension, the contralateral kidney of post-Goldblatt hypertensive and post-Goldblatt normotensive rats excretes more vasoconstrictive thromboxane in comparison to controls, whereas excretion of vasodilatory prostaglandin is not elevated. However, increased TXB2 excretion and the absence of an increase in PGE2 excretion from the contralateral kidney do not appear to be important for the maintenance of high blood pressure in this model of renovascular hypertension.