Biomedical subjects

R Curi

Publications and source records attributed to R Curi.

At least 19 recordsLinked to original sources

PubMed2006

Glucose, palmitate and pro-inflammatory cytokines modulate production and activity of a phagocyte-like NADPH oxidase in rat pancreatic islets and a clonal beta cell line.

AIMS/HYPOTHESIS: Acute or chronic exposure of beta cells to glucose, palmitic acid or pro-inflammatory cytokines will result in increased production of the p47(phox) component of the NADPH oxidase and subsequent production of reactive oxygen species (ROS). METHODS: Rat pancreatic islets or clonal rat BRIN BD11 beta cells were incubated in the presence of glucose, palmitic acid or pro-inflammatory cytokines for periods between 1 and 24 h. p47(phox) production was determined by western blotting. ROS production was determined by spectrophotometric nitroblue tetrazolium or fluorescence-based hydroethidine assays. RESULTS: Incubation for 24 h in 0.1 mmol/l palmitic acid or a pro-inflammatory cytokine cocktail increased p47(phox) protein production by 1.5-fold or by 1.75-fold, respectively, in the BRIN BD11 beta cell line. In the presence of 16.7 mmol/l glucose protein production of p47(phox) was increased by 1.7-fold in isolated rat islets after 1 h, while in the presence of 0.1 mmol/l palmitic acid or 5 ng/ml IL-1beta it was increased by 1.4-fold or 1.8-fold, respectively. However, palmitic acid or IL-1beta-dependent production was reduced after 24 h. Islet ROS production was significantly increased after incubation in elevated glucose for 1 h and was completely abolished by addition of diphenylene iodonium, an inhibitor of NADPH oxidase or by the oligonucleotide anti-p47(phox). Addition of 0.1 mmol/l palmitic acid or 5 ng/ml IL-1beta plus 5.6 mmol/l glucose also resulted in a significant increase in islet ROS production after 1 h, which was partially attenuated by diphenylene iodonium or the protein kinase C inhibitor GF109203X. However, ROS production was reduced after 24 h incubation. CONCLUSIONS/INTERPRETATION: NADPH oxidase may play a key role in normal beta cell physiology, but under specific conditions may also contribute to beta cell demise.

Animals↗

PubMed2006

Crotoxin induces actin reorganization and inhibits tyrosine phosphorylation and activity of small GTPases in rat macrophages.

Crotoxin is the main neurotoxic component of Crotalus durissus terrificus snake venom. Previous work of our group demonstrated that this toxin or its phospholipase A(2) subunit inhibits macrophage spreading and phagocytosis. The phagocytic activity of macrophages is controlled by the rearrangement of actin cytoskeleton and activity of the small Rho GTPases. The effect of crotoxin and its subunit on actin reorganization and tyrosine phosphorylation in rat peritoneal macrophages, during phagocytosis of opsonized zymosan, was presently investigated. The crude venom was used as positive control. In addition, the effect of crotoxin on the activity of Rho and Rac1 small GTPases was examined. Transmission electron studies showed that the venom or crotoxin decreased the extent of spread cells and increased microprojections often extended from macrophage surface. Immunocytochemical assays demosntrated that the venom or toxins increased F-actin content in the cytoplasm of these cells, but induced a marked decrease of phosphotyrosine. These effects were abolished by treatment with zileuton, a 5-lipoxygenase inhibitor. Furthermore, crotoxin decreased membrane-associated RhoA and Rac1 in translocation assays. The present results indicate that the crotalid venom and crotoxin are able to induce cytoskeleton rearrangement in macrophages. This effect is associated with inhibition of tyrosine phosphorylation and of the activity of proteins involved in intracellular signalling pathways important for the complete phagocytic activity of these cells.

Actins↗

PubMed2006

Diabetes causes marked changes in function and metabolism of rat neutrophils.

Several studies have shown impairment of neutrophil function, a disorder that contributes to the high incidence of infections in diabetes. Since glucose and glutamine play a key role in neutrophil function, we investigated their metabolism in neutrophils obtained from the peritoneal cavity of streptozotocin-induced diabetic rats. The activities of hexokinase, glucose-6-phosphate dehydrogenase (G6PDH), phosphofructokinase (PFK), citrate synthase, phosphate-dependent glutaminase, NAD+-linked and NADP+-linked isocitrate dehydrogenase were assayed. Glucose, glutamine, lactate, glutamate and aspartate, and the decarboxylation of [U-14C], [1-14C] and [6-14C]glucose; [U-14C]palmitic acid; and [U-14C]glutamine were measured in 1-h incubated neutrophils. Phagocytosis capacity and hydrogen peroxide (H2O2) production were also determined. All measurements were carried out in neutrophils from control, diabetic and insulin-treated (2-4 IU/day) diabetic rats. Phagocytosis and phorbol myristate acetate (PMA)-stimulated H2O2 production were decreased in neutrophils from diabetic rats. The activities of G6PDH and glutaminase were decreased, whereas that of PFK was raised by the diabetic state. The activities of the remaining enzymes were not changed. Diabetes decreased the decarboxylation of [1-14C]glucose and [U-14C]glutamine; however, [6-14C]glucose and [U-14C]palmitic acid decarboxylation was increased. These observations indicate that changes in metabolism may play an important role in the impaired neutrophil function observed in diabetes. The treatment with insulin abolished the changes induced by the diabetic state even with no marked change in glycemia. Therefore, insulin may have a direct effect on neutrophil metabolism and function.

Animals↗

PubMed2005

Lipoxygenase-derived eicosanoids are involved in the inhibitory effect of Crotalus durissus terrificus venom or crotoxin on rat macrophage phagocytosis.

Crotalus durissus terrificus snake venom and its major toxin, crotoxin or type II PLA2 subunit of this toxin, induce an inhibitory effect on spreading and phagocytosis in 2h incubated macrophages. The involvement of arachidonate-derived mediators on the inhibitory action of the venom or toxins on rat peritoneal macrophage phagocytosis was presently investigated. Peritoneal cells harvested from naive rats and incubated with the venom or toxins or harvested from the peritoneal cavity of rats pre-treated with the toxins were used. Zileuton, a 5-lipoxygenase inhibitor but not indomethacin, a cyclooxygenase inhibitor, given in vivo and in vitro abolished the inhibitory effect of venom or toxins on phagocytosis. Resident peritoneal macrophages incubated with the venom or toxins showed increased levels of prostaglandin E2 and lipoxin A4, with no change in leukotriene B4. These results suggest that lipoxygenase-derived eicosanoids are involved in the inhibitory effect of C.d. terrificus venom, crotoxin or PLA2 on macrophage phagocytosis.

Animals↗

PubMed2005

Role of insulin on PGE2 generation during LPS-induced lung inflammation in rats.

Alterations in arachidonic acid (AA) metabolism have been reported to occur in diabetes mellitus. The present study was carried out to verify if these alterations are due to the relative lack of insulin or to high levels of blood glucose. Male Wistar rats were rendered diabetic by alloxan injection (42 mg/kg, i.v.), 10 or 30 days before the experiments. Some diabetic rats received a single dose (4 IU, s.c.) of NPH insulin 2 h before an intratracheal instillation of lipopolysaccharide (LPS, 750 microg) or saline. Six hours after LPS challenge, the following parameters were analysed: blood glucose levels, total and differential leukocyte counts in bronchoalveolar lavage (BAL) fluid; linoleic acid and AA content in blood neutrophils (HPLC), and levels of prostaglandin (PG)E(2) in BAL (ELISA). Relative to controls, a reduced number of neutrophils (18%) and decreased amounts of PGE(2) (40%) were observed in the BAL fluid of diabetic rats in response to LPS. A single dose of insulin was not able to reduce blood sugar levels to normal values, but instead resulted in the normalization of both leukocyte migration to the lungs and levels of PGE(2). Accordingly, these abnormalities might be primarily linked to a continuing insulin deficiency rather than to secondary hyperglycaemia occurring in the diabetic rat. In conclusion, data presented suggest that insulin might regulate neutrophil migration and generation of PGE(2) during the course of acute lung injury induced by LPS.

Alloxan↗

PubMed2005

Molecular mechanisms of glutamine action.

Glutamine is the most abundant free amino acid in the body and is known to play a regulatory role in several cell specific processes including metabolism (e.g., oxidative fuel, gluconeogenic precursor, and lipogenic precursor), cell integrity (apoptosis, cell proliferation), protein synthesis, and degradation, contractile protein mass, redox potential, respiratory burst, insulin resistance, insulin secretion, and extracellular matrix (ECM) synthesis. Glutamine has been shown to regulate the expression of many genes related to metabolism, signal transduction, cell defense and repair, and to activate intracellular signaling pathways. Thus, the function of glutamine goes beyond that of a simple metabolic fuel or protein precursor as previously assumed. In this review, we have attempted to identify some of the common mechanisms underlying the regulation of glutamine dependent cellular functions.

Animals↗

PubMed2005

Inhibitory effect of phospholipase A(2) isolated from Crotalus durissus terrificus venom on macrophage function.

Recent work demonstrated that crotoxin, the main toxin of Crotalus durissus terrificus venom, inhibits macrophage spreading and phagocytic activities. The crotoxin molecule is composed of two subunits, an acidic non-toxic and non-enzymatic polypeptide named crotapotin and a weakly toxic basic phospholipase A(2) (PLA(2)). In the present work, the active subunit responsible for the inhibitory effect of crotoxin on macrophage function was investigated. Peritoneal macrophages harvested from naive rats were used. Crotapotin (2.12, 3.75, or 8.37nM/ml), added for 2h to the medium of peritoneal cell incubation, did not modify the spreading and phagocytic activities of these cells. On the other hand, the PLA(2) (1.43, 2.86, or 6.43nM/ml) subunit caused a significant reduction (30, 33, and 35%, respectively) of the spreading activity. The PLA(2) also inhibited the phagocytosis of opsonised zymosan, opsonised sheep erythrocytes, and Candida albicans, indicating that this inhibitory effect is not dependent on the type of receptor involved in the phagocytosis process. The inhibitory effect of PLA(2) was not due to loss of cell membrane integrity, since macrophage viability was higher than 95%. These findings indicate that the inhibitory effect of crotoxin on macrophage spreading and phagocytic activities is caused by the phospholipase A(2) subunit.

Analysis of Variance↗

PubMed2004

Effect of Cysticercus cellulosae on neutrophil function and death.

Neutrophils, eosinophils and macrophages interact with invading parasites and naive hosts. The initial reaction of leukocytes is the generation of reactive oxygen species (ROS). The cytotoxic effects of extracts derived from intact Cysticercus cellulosae and from the scolex or membrane fractions on neutrophils were examined. DNA fragmentation of neutrophils was observed when cells were incubated with an extract from the intact metacestode; however, the addition of antioxidant enzymes to the incubation medium had a protective effect. The scolex and membrane extracts did not affect DNA fragmentation of neutrophils. Hydrogen peroxide production of neutrophils incubated with metacestode fractions from C. cellulosae increased by 190% (total extract), 120% (scolex) or 44% (membrane). An increase in antioxidant catalase activity (28%) concomitant with the increased production of ROS was observed in neutrophils incubated with metacestode fractions, which could be an attempt at self-protection. ROS production by neutrophils in the presence of the intact cysticerci extract did not alter phagocytosis. In contrast, the scolex and membrane fractions increased the phagocytic capacity of neutrophils by 44 and 28%, respectively. The results showed that the extract from intact C. cellulosae was toxic for neutrophils via ROS production, leading to DNA fragmentation and inhibition of phagocytic capacity, but neutrophils are able to protect themselves against oxidative stress by via catalase activity.

Animals↗

PubMed2004

Effect of bullfrog (Rana catesbeiana) oil administered by gavage on the fatty acid composition and oxidative stress of mouse liver.

The aim of the present study was to investigate the effects of daily intragastric administration of bullfrog oil (oleic, linoleic and palmitoleic acid-rich oil), corresponding to 0.4% of body weight for four weeks, on fatty acid composition and oxidative stress (lipid peroxidation and catalase activity) in mouse liver. The activities of aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT), biomarkers of tissue injury, were determined in liver homogenates and serum. The proportions of 18:2n-6, 20:4n-6, 20:5n-3, and 22:6n-3 (polyunsaturated fatty acids, from 37 to 60%) in the total fatty acid content were increased in the liver of the bullfrog oil-treated group (P < 0.05) compared to control. At the same time, a significant decrease in the relative abundance of 14:0, 16:0, and 18:0 (saturated fatty acids, from 49 to 25%) was observed. The hepatic content of thiobarbituric acid reactive substances (TBARS) was increased from 2.3 +/- 0.2 to 12.3 +/- 0.3 nmol TBA-MDA/mg protein and catalase activity was increased from 840 +/- 32 to 1110 +/- 45 micromol reduced H2O2 min-1 mg protein-1 in the treated group. Bullfrog oil administration increased AST and ALP activities in the liver (from 234.10 +/- 0.12 to 342.84 +/- 0.13 and 9.38 +/- 0.60 to 20.06 +/- 0.27 U/g, respectively) and in serum (from 95.41 +/- 6.13 to 120.32 +/- 3.15 and 234.75 +/- 11.5 to 254.41 +/- 2.73 U/l, respectively), suggesting that this treatment induced tissue damage. ALT activity was increased from 287.28 +/- 0.29 to 315.98 +/- 0.34 U/g in the liver but remained unchanged in serum, whereas the GGT activity was not affected by bullfrog oil treatment. Therefore, despite the interesting modulation of fatty acids by bullfrog oil, a possible therapeutic use requires care since some adverse effects were observed in liver.

Alkaline Phosphatase↗

PubMed2004

Cholesterol induces fetal rat enterocyte death in culture.

The effect of cholesterol on fetal rat enterocytes and IEC-6 cells (line originated from normal rat small intestine) was examined. Both cells were cultured in the presence of 20 to 80 microM cholesterol for up to 72 h. Apoptosis was determined by flow cytometric analysis and fluorescence microscopy. The expression of HMG-CoA reductase and peroxisome proliferator-activated receptor gamma (PPARgamma) was measured by RT-PCR. The addition of 20 microM cholesterol reduced enterocyte proliferation as early as 6 h of culture. Reduction of enterocyte proliferation by 28 and 41% was observed after 24 h of culture in the presence and absence of 10% fetal calf serum, respectively, with the effect lasting up to 72 h. Treatment of IEC-6 cells with cholesterol for 24 h raised the proportion of cells with fragmented DNA by 9.7% at 40 microM and by 20.8% at 80 microM. When the culture period was extended to 48 h, the effect of cholesterol was still more pronounced, with the percent of cells with fragmented DNA reaching 53.5% for 40 microM and 84.3% for 80 microM. Chromatin condensation of IEC-6 cells was observed after treatment with cholesterol even at 20 microM. Cholesterol did not affect HMG-CoA reductase expression. A dose-dependent increase in PPARgamma expression in fetal rat enterocytes was observed. The expression of PPAR-gamma was raised by 7- and 40-fold, in the presence and absence of fetal calf serum, respectively, with cholesterol at 80 mM. The apoptotic effect of cholesterol on enterocytes was possibly due to an increase in PPARgamma expression.

Animals↗

PubMed2004

Evidence that arachidonic acid derived from neutrophils and prostaglandin E2 are associated with the induction of acute lung inflammation by lipopolysaccharide of Escherichia coli.

OBJECTIVE: The involvement of arachidonic acid (AA) and PGE2 during the E. coli lipopolysaccharide (LPS)-induced acute lung injury was investigated. MATERIAL: Adult male Wistar rats were used. For in vitro studies, rat neutrophils, bronchoalveolar lavage (BAL) fluid, and lug vascular endothelium were used, as described below. TREATMENT: Rats were given an intratracheal injection of LPS (750 microg). METHODS: Total and differential cell counts in BAL fluid; enzyme-linked immunoassay (ELISA) analyses of TNF-alpha, IL-1beta, LTB4 and PGE2 in BAL, and immunohistochemical detection of ICAM-1 on lung vascular endothelium were performed six h after LPS challenge. Fatty acid composition of blood neutrophils and plasma was analyzed by HPLC. RESULTS: Rats instilled with LPS presented a sixty three-fold increase in the number of neutrophils in BAL (from 0.5 x 10(6) to 31.5 x 10(6) cells), accompanied by increased levels of TNF-alpha and IL-1beta (p < 0.001), and a three-fold increase in ICAM-1 expression on vascular endothelium. The content of AA in blood neutrophils was reduced by 50%, whereas the level of PGE2 in BAL was increased by 3.5 fold, without changes in the levels of LTB4. CONCLUSIONS: These findings suggest that AA and PGE2 are associated with LPS challenge.

Acute Disease↗

PubMed2004

Effects of palmitic acid and cholesterol on proton transport across black lipid membranes.

We studied the effect of palmitic acid (PA) and cholesterol (approximately 17 wt.%) on proton translocation across asolectin (charged) and diphytanoylphosphatidylcholine (DPhPC, neutral) black lipid membranes (BLMs). Potential difference (PD), short circuit current (SCC), and conductance (G(total)) were measured with a digital electrometer. Membranes were exposed to pH gradients (0.4-2.0 units), followed by PA addition to bath (symmetrically, 40-65 microM). The membrane conductive pathway was subdivided into an unspecific and a proton-related routes. A computer program estimated the conductances (G(un) and G(H)) of the two pathways from the measured parameters. No significant differences in proton selectivity were found between DPhPC membranes and DPhPC/cholesterol membranes. By contrast, cholesterol incorporation into asolectin increases membranes selectivity to proton. Cholesterol dramatically reduced G(un) reflecting, probably, its ability of inducing order in lipid chains. In asolectin membranes, PA increases proton selectivity, probably by acting as a proton shuttle according to the model proposed by Kamp and et al. [Biochemistry 34 (1995) 11928]. Cholesterol incorporation into asolectin membranes eliminates the PA-induced increase in proton selectivity. In DPhPC and DPhPC/cholesterol membranes, PA does not affect proton selectivity. These results are discussed in terms of the presence of cardiolipin (CL) in asolectin, cholesterol/PA interactions, and cholesterol order-inducing effects on acyl-chains.

Cell Membrane↗

PubMed2004

Changes of fatty acid composition in incubated rat pancreatic islets.

OBJECTIVE: The hypothesis that changes in fatty acId composition of pancreatic islets occur during incubation was investigated. METHODS: The content and composition of fatty acIds (FA) from rat pancreatic islets and culture medium after incubation for 1 and 3 hours in the absence or in the presence of 5.6, 8.3, or 16.7 mM glucose were determined by HPLC analysis. RESULTS: The FA content of pancreatic islets was reduced after 1 hour incubation in the absence of glucose. However, the total FA content was restored by incubating in the presence of 5.6 mM glucose and exceeded by incubating in the presence of 8.3 mM or 16.7 mM glucose. Saturated FA contributed a substantially greater proportion of the total FA increase in comparison to unsaturated FA, being palmitic and stearic acIds the most important. The total lipId content of pancreatic islets was not increased if the period of incubation in the presence of glucose was extended to 3 hours. A substantial amount of FA was found in the medium after 1 hour incubation in the absence of glucose: 141 ng per 80 islets for saturated and 75 ng per 80 islets for unsaturated. The release of FA from islets is increased in the presence of glucose. CONCLUSION: The release of FA from islets is a novel finding and may be related to modulation of B-cell function.

Animals↗

PubMed2004

Effects of fish oil on the central nervous system: a new potential antidepressant?

In the last 100 years major depression has increased worldwide. In this study we provided coconut fat (CF, rich in saturated fatty acids) or fish oil (FO, rich in n-3 polyunsaturated fatty acids) to female rats throughout pregnancy and lactation and then to their offspring post-weaning and examined lipid brain profile and the possible effect of FO as antidepressant agent in the offspring in adulthood (F1). Rats were submitted to forced swimming test, elevated plus maze, Morris water maze and open field. Peroxidation rate in the cerebral cortex and hippocampus were measured. Docosahexaenoic acid (DHA) concentration in dam's milk, eicosapentaenoic acid (EPA) and DHA concentration in hippocampus and cerebral cortex from F1 rats FO supplemented increased significantly when compared to control (C) and CF rats. Arachidonic acid/EPA ratio in the cerebral cortex and hippocampus decreased in rats submitted to forced swimming test. Peroxidation rate were not different between the groups. Immobility time in the forced swimming test in FO group was reduced (p < 0.01) when compared to C and CF rats. We conclude that lifelong intake of FO was able to induce an antidepressant effect with EPA and DHA concentration increased in the cerebral cortex and hippocampus.

Animals↗

PubMed2004

Diabetes induces apoptosis in lymphocytes.

The occurrence of DNA fragmentation in lymphocytes obtained from alloxan-induced diabetic rats and diabetic patients was investigated. A high proportion of apoptotic lymphocytes in diabetic states may explain the impaired immune function in poorly controlled diabetic patients. Rat mesenteric lymph node lymphocytes were analysed for DNA fragmentation by using flow cytometry and agarose gel, and for chromatin condensation by Hoescht 33342 staining under different situations. Immediately after being obtained, the proportion of lymphocytes with fragmented DNA was twofold higher in alloxan-induced diabetic rats than in cells from control rats. After 48 h in culture, the occurrence of DNA fragmentation was also higher (81%) in cells from diabetic rats. Hoescht staining and fragmented DNA visualized in agarose gel were also higher in lymphocytes from alloxan-induced diabetic rats than in control cells. To investigate if this phenomenon also occurs in humans, blood lymphocytes from 14 diabetic subjects were examined. Similar results to those of rat lymphocytes were found in cells from diabetic patients immediately after being obtained and after 48 h in culture. The high occurrence of apoptosis in lymphocytes was accompanied by a reduced number of blood-circulating lymphocytes in diabetic patients. The involvement of low insulinaemia for the occurrence of apoptosis in lymphocytes was also examined. Insulin treatment markedly reduced the proportion of lymphocytes with fragmented DNA in alloxan-induced diabetic rats.

Adolescent↗

PubMed2003

Naproxen, clenbuterol and insulin administration ameliorates cancer cachexia and reduce tumor growth in Walker 256 tumor-bearing rats.

Cancer cachexia is characterized by anorexia and intense peripheral catabolism. We examine the potential benefits of combination of different anabolic agents such as insulin and clenbuterol associated to prostaglandin synthesis inhibitor (naproxen) on tumor growth, cachexia and renal function in Walker 256 tumor-bearing rats (WK). Groups were separated into WK, and WK with naproxen (WK N) or naproxen plus clenbuterol (WK NCb) or naproxen plus clenbuterol plus insulin (WK NCbI). Treatment begins at the 4th day after tumor inoculation, at the 14th day they were killed, glycemia, lacticidemia, glycogen content from liver, soleus and gastrocnemius muscles, tumor mass, body weight and kidney function were determined. Glycemia and glycogen content were reduced and lacticidemia increased in WK (p<0.05) as compared to control rats. The glycogen content recovered in all treated groups. Tumor weight was significantly reduced by the different treatments. At the 14th weight change (carcass-initial body weight) in the control increased by 38% and in the WK -2%. Naproxen treatment (WK N) induced an increased by 14%. The inclusion of clenbuterol (WK NCb) and insulin (WK NCbI) by 38 and 41%, respectively. Mean glomerular filtration rate (GFR) increased in the WK (p<0.05) as compared to control, but in the WK NCb the GFR was similar to control. Our results suggest that naproxen is able to reduce tumor growth and its association with insulin and clenbuterol induce mass weight gain and recovery energy fuel.

Adrenergic beta-Agonists↗

PubMed2003

Arachidonic acid triggers an oxidative burst in leukocytes.

The change in cellular reducing potential, most likely reflecting an oxidative burst, was investigated in arachidonic acid- (AA) stimulated leukocytes. The cells studied included the human leukemia cell lines HL-60 (undifferentiated and differentiated into macrophage-like and polymorphonuclear-like cells), Jurkat and Raji, and thymocytes and macrophages from rat primary cultures. The oxidative burst was assessed by nitroblue tetrazolium reduction. AA increased the oxidative burst until an optimum AA concentration was reached and the burst decreased thereafter. In the leukemia cell lines, optimum concentration ranged from 200 to 400 microM (up to 16-fold), whereas in rat cells it varied from 10 to 20 microM. Initial rates of superoxide generation were high, decreasing steadily and ceasing about 2 h post-treatment. The continuous presence of AA was not needed to stimulate superoxide generation. It seems that the NADPH oxidase system participates in AA-stimulated superoxide production in these cells since the oxidative burst was stimulated by NADPH and inhibited by N-ethylmaleimide, diphenyleneiodonium and superoxide dismutase. Some of the effects of AA on the oxidative burst may be due to its detergent action. There apparently was no contribution of other superoxide-generating systems such as xanthine-xanthine oxidase, cytochromes p-450 and mitochondrial electron transport chain, as assessed by the use of inhibitors. Eicosanoids and nitric oxide also do not seem to interfere with the AA-stimulated oxidative burst since there was no systematic effect of cyclooxygenase, lipoxygenase or nitric oxide synthase inhibitors, but lipid peroxides may play a role, as indicated by the inhibition of nitroblue tetrazolium reduction promoted by tocopherol.

Animals↗

PubMed2003

L- and DL-carnitine induce tetanic fade in rat neuromuscular preparation.

Carnitine, a structurally choline-like metabolite, has been used to increase athletic performance, although its effects on neuromuscular transmission have not been investigated. It is present in skeletal muscle and its plasma levels are about 30 to 90 micro M. Using rat phrenic nerve diaphragm preparations indirectly and directly stimulated with high rate pulses, D-carnitine (30 and 60 micro M), L-carnitine (60 micro M) and DL-carnitine (60 micro M) were shown to induce tetanic fade (D-carnitine = 19.7 +/- 3.1%, N = 6; L-carnitine = 16.6 +/- 2.4%, N = 6; DL-carnitine = 14.9 +/- 2.1%, N = 6) without any reduction of maximal tetanic tension. D-carnitine induced tetanic fade in neuromuscular preparations previously paralyzed with d-tubocurarine and directly stimulated. The effect was greater than that obtained by indirect muscle stimulation. Furthermore, previous addition of atropine (20 to 80 micro M) to the bath did not reduce carnitine isomer-induced tetanic fade. In contrast to D-carnitine, the tetanic fade induced by L- and DL-carnitine was antagonized by choline (60 micro M). The combined effect of carnitine isomers and hemicholinium-3 (0.01 nM) was similar to the effect of hemicholinium-3 alone. The data suggest that L- and DL-carnitine-induced tetanic fade seems to depend on their transport into the motor nerve terminal.

Animals↗