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At least 595 records · Page 33Linked to original sources
PubMed2005

Effect of ethanol on the response of the rat urinary bladder to in vitro ischemia: protective effect of alpha-lipoic acid.

PURPOSE: Ethanol exposure has been used to demonstrate the increase of oxidative stress to a variety of tissues. We studied the effect of ethanol on the response of isolated strips of rat bladder to in vitro hypoxia in the absence of glucose (in vitro ischemia). Secondly, we determined if alpha-lipoic acid (LA) could alter the response to ethanol + in vitro ischemia. METHODS: Sixty-four rats were used for the these experiments. Each rat was anesthetized and its urinary bladder excised. The bladder body was cut into two longitudinal strips and each strip mounted in individual baths filled with oxygenated Tyrodes solution containing glucose at 37 degrees C. Ethanol (0.3%, 1%, or 3%) was placed in the first six baths (two strips at each concentration). The last two baths did not receive ethanol. Each strip was incubated for 1 h and then stimulated with field stimulation at 2, 8, and 32 Hz. Each strip was stimulated with 10 microM carbachol, washed three times with fresh oxygenated buffer and ethanol re-added to their respective baths. Each strip was then stimulated with 120 mM KCl and washed three times as before. Strips were then subjected to 1 h in vitro ischemia (incubation in the absence of glucose with Tyrode's equilibrated with nitrogen instead of oxygen). During the ischemic period, each strip was stimulated for 5 s every 10 min by 32 Hz FS to simulate hyperreflexia. At the end of the hour, the tissues were incubated for an additional hour in the presence of oxygen + glucose and subjected to a second series of stimulations as before. At all times, ethanol was maintained in baths 1-6. In set 2, 1% ethanol was added to the first six baths. LA was added to every other bath, and the experiments performed as mentioned earlier. RESULTS: (a) Ethanol at 0.3% or 1% had no effect on the contractile responses prior to exposure to in vitro ischemia; 3% was inhibitory. (b) In vitro ischemia mediated a significant decrease in the contractile responses to all forms of stimulation except for carbachol. (c) Ethanol mediated a dose-response enhancement of the contractile dysfunctions caused by in vitro ischemia. (d) LA completely reversed the effects of ethanol on contractile responses following in vitro ischemia except for carbachol. CONCLUSIONS: The results demonstrate that direct exposure to ethanol significantly enhanced contractile dysfunctions mediated by in vitro ischemia followed by re-oxygenation and that the presence of LA significantly inhibits this effect of ethanol.

Animals↗
PubMed2001

The effects of treatment with alpha-lipoic acid or evening primrose oil on vascular hemostatic and lipid risk factors, blood flow, and peripheral nerve conduction in the streptozotocin-diabetic rat.

Oxidative stress and defective fatty acid metabolism in diabetes may lead to impaired nerve perfusion and contribute to the development of peripheral neuropathy. We studied the effects of 2-week treatments with evening primrose oil (EPO; n = 16) or the antioxidant alpha-lipoic acid (ALA; n = 16) on endoneurial blood flow, nerve conduction parameters, lipids, coagulation, and endothelial factors, in rats with streptozotocin-induced diabetes. Compared with their nondiabetic littermates, untreated diabetic rats had impaired sciatic motor and saphenous sensory nerve-conduction velocity (NCV; P <.001), reduced endoneurial blood flow (P <.001), and increased serum triglycerides (P <.01), cholesterol (P < 0.01), plasma factor VII (P <.0001), and von Willebrand factor (vWF; P <.0001). Plasma fibrinogen and serum high-density lipoprotein concentrations were not significantly different. Treatment with either ALA or EPO effectively corrected the deficits in NCV and endoneurial blood flow. ALA was associated with marked and statistically significant decreases in fibrinogen, factor VII, vWF, and triglycerides (P <.01, paired t tests before v after treatment). In contrast, EPO was associated with significant (P <.05) increases in fibrinogen, factor VII, vWF, triglycerides, and cholesterol and a significant decrease in high-density lipoprotein. Changes in levels of coagulation factors and lipids, qualitatively similar to those found with EPO, were obtained with a diet containing sunflower oil (to control for calorific and lipid content) or with a normal diet alone. Blood glucose and hematocrit levels were not significantly altered by treatments. These data suggest that although both ALA and EPO improve blood flow and nerve function, their actions on vascular factors differ. The marked effects of ALA in lowering lipid and hemostatic risk factors for cardiovascular disease indicate potential antithrombotic and antiatherosclerotic actions that could be of benefit in human diabetes and merit further study.

Animals↗
PubMed2001

[Berlition R 300 oral -- alpha-lipoic acid preparation for the correction of body changes associated with high serum iron content].

Medication Berlition 300 oral, produced by "Berlin-Hemie", induces lower serum iron content, decrease in transferrin content of whole blood and serum proportionally to increased urinary iron excretion and lower serum bilirubin and normalizes serum glucose level. Berlition 300 oral, lipoic acid preparation made by "Berlin-He mie" (Menarini group), could be recommended for treatment of high serum iron content and iron overload, especially in association with diabetes mellitus.

Adult↗
PubMed2006

Alpha-lipoic acid modulates ovarian surface epithelial cell growth.

OBJECTIVE: The intracellular redox state plays an important role in controlling inflammation. Clinical and laboratory data suggest that inflammation can lead to tumor progression. We hypothesized that restoring intracellular redox control would inhibit inflammation and subsequently tumor progression. Our studies were designed to investigate the effect of alpha-lipoic acid (ALA), a naturally occurring antioxidant, on a key inflammatory signaling pathway and cell proliferation in normal and tumorigenic ovarian surface epithelial cells. METHODS: Normal and tumorigenic ovarian surface epithelial cells were isolated as described by Roby and coworkers [Roby KF, Taylor CC, Sweetwood JP, Cheng Y, Pace JL, Tawpik O, Persons DL, Smith PG, Terranova PF, Development of a syngeneic mouse model for events related to ovarian cancer. Carcinogen 2000;21 (4):585. [1]]. The effect of ALA on cellular function was measured in cell proliferation and apoptosis assays. p27(kip1) protein levels were measured by Western analysis. Activation of NF-kappaB dependent transcription was assessed in cell cultures transiently transfected with NF-kappaB controlled reporter constructs. RESULTS: Our results reveal that ALA selectively inhibits the growth of tumorigenic as compared to non-tumorigenic ovarian surface epithelial cells. The growth inhibitory effect of ALA is not due to induction of apoptosis but instead is associated with an increase in the half-life of the cyclin-dependent kinase inhibitor, p27(kip1). In parallel to the growth inhibitory effect, ALA also affects a key inflammatory signaling pathway by inhibiting TNFalpha-induced NF-kappaB signaling activity. CONCLUSIONS: Our studies are the first to show that ALA treatment has a growth inhibitory effect on malignant surface epithelial cells of ovarian origin. We have also confirmed the reproducibility of the immunocompetent mouse ovarian cancer model originally described by Roby and coworkers [Roby KF, Taylor CC, Sweetwood JP, Cheng Y, Pace JL, Tawpik O, Persons DL, Smith PG, Terranova PF, Development of a syngeneic mouse model for events related to ovarian cancer. Carcinogen 2000;21 (4):585].

Animals↗
PubMed2001

Effects of vitamin E and alpha-lipoic acid on skeletal muscle contractile properties.

Initial experiments were conducted using an in situ rat tibialis anterior (TA) muscle preparation to assess the influence of dietary antioxidants on muscle contractile properties. Adult Sprague-Dawley rats were divided into two dietary groups: 1) control diet (Con) and 2) supplemented with vitamin E (VE) and alpha-lipoic acid (alpha-LA) (Antiox). Antiox rats were fed the Con rats' diet (AIN-93M) with an additional 10,000 IU VE/kg diet and 1.65 g/kg alpha-LA. After an 8-wk feeding period, no differences existed (P > 0.05) between the two dietary groups in maximum specific tension before or after a fatigue protocol or in force production during the fatigue protocol. However, in unfatigued muscle, maximal twitch tension and tetanic force production at stimulation frequencies < or = 40 Hz were less (P < 0.05) in Antiox animals compared with Con. To investigate which antioxidant was responsible for the depressed force production, a second experiment was conducted using an in vitro rat diaphragm preparation. Varying concentrations of VE and dihydrolipoic acid, the reduced form of alpha-LA, were added either individually or in combination to baths containing diaphragm muscle strips. The results from these experiments indicate that high levels of VE depress skeletal muscle force production at low stimulation frequencies.

Animals↗
PubMed2004

Influence of alpha-lipoic acid on lipid peroxidation and antioxidant defence system in blood of insulin-resistant rats.

BACKGROUND: High fructose feeding induces insulin resistance and hyperinsulinaemia in rats. A role for oxidative stress in the occurrence of insulin resistance has been suggested by several workers. AIM: The aim of this study was to investigate the effect of alpha-lipoic acid (LA) on oxidant-antioxidant balance in rats fed on a high-fructose diet that showed characteristic features of insulin resistance. METHODS: Male Wistar rats weighing 150-170 g were divided into seven groups. The control group received the control diet containing starch. The fructose group was given a high-fructose diet (>60% of total calories). The third and fourth groups were given fructose diet and were administered two different doses of LA at a low dose (35 mg/kg body weight) and high dose (70 mg/kg body weight) using olive oil as vehicle. The fifth group received fructose diet and olive oil. The sixth group received control diet and was administered LA (70 mg/kg body weight). And, the seventh group received the control diet and olive oil. Products of lipid peroxidation and activities of enzymic antioxidants, namely superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and glutathione reductase, in red blood cells were assayed. Levels of non-enzymic antioxidants alpha-tocopherol, ascorbic acid and reduced glutathione were determined in plasma. RESULTS: The levels of lipid peroxides, diene conjugates and thiobarbituric acid-reactive substances were significantly higher in fructose-fed rats. Inadequate antioxidant system was observed in high-fructose-fed rats. Treatment of fructose rats mitigated the imbalance between peroxidation and antioxidant defence system at both the doses tested. Increases in glucose, triglycerides, free fatty acids, insulin and insulin resistance were observed in fructose-fed rats. LA administration prevented these alterations and improved insulin sensitivity. Significant positive correlations were obtained between insulin resistance and lipid peroxidation indices. CONCLUSIONS: Increased lipid peroxidation and deficient antioxidant system are observed in high-fructose-fed rats. LA administration preserves the antioxidant system and lowers lipid peroxidation. The findings suggest an interrelationship between lipid peroxidation and insulin resistance.

Animals↗
PubMed2005

Effects of supplementation with alpha-lipoic acid on exercise-induced activation of coagulation.

Physical exercise leads to minor activation of blood coagulation, which appears to be balanced by a concomitant activation of the fibrinolytic system. The mechanisms underlying this physiological phenomenon are still unknown. To evaluate the role of oxidative stress for exercise-induced activation of coagulation, we investigated if supplementation with alpha -lipoic acid (LA) as an antioxidant reduces the hemostatic response to exercise. Ten young men (age, 25 +/- 4 years; maximal oxygen consumption [V o 2 max], 61 +/- 6 mL/(kg min) [mean +/- SD]) were subjected to a 1-hour run on a treadmill at a velocity corresponding to an oxygen demand of 75% to 80% of maximum (anaerobic threshold). Exercise testing was repeated in the same subjects after supplementation with LA (1200 mg/d PO) for 10 days. Molecular markers of thrombin (prothrombin fragment 1 + 2, thrombin-antithrombin complexes) and fibrin formation (fibrinopeptide A) as well as markers of the fibrinolytic activity (tissue-plasminogen activator, plasmin-antiplasmin complexes, d -dimers) and of lipid peroxidation (malondialdehyde) were determined before and immediately after exercise. Supplementation therapy with LA had no effect on hemostatic and fibrinolytic variables either at rest or in response to exercise. Likewise, concentrations of malondialdehyde at rest and after exercise were not influenced by LA. In summary, the hemostatic response to exercise is not affected by supplementation with LA in young healthy male individuals. The role of oxidative stress for exercise-induced activation of coagulation has to be defined in further studies.

Adult↗
PubMed2006

Salubrious effects of lipoic acid against adriamycin-induced clastogenesis and apoptosis in Wistar rat bone marrow cells.

Adriamycin (ADR), an anthracycline antibiotic, which is widely used as an antineoplastic drug in the treatment of various solid tumors, has been shown to induce genotoxicity in erythropoietic system. The aim of the present study was to investigate the protective efficacy of DL-alpha-lipoic acid (LA) on ADR-induced clastogenicity and apoptosis in the bone marrow of rats. The animals were randomly divided into eight groups consisting of six rats each. Five groups were administered ADR (20 mg/kg body weight, i.v.) to induce genotoxicity; four of these groups received a single intraperitoneal injection of LA at a dose of either 100 or 200 mg/kg body weight, and either 30 or 60 min prior to ADR administration. A vehicle treated control group and LA control groups were also included. The beneficial effects of LA were monitored by DNA strand breaks, chromosomal aberrations, micronucleus assay and apoptotic studies in the bone marrow cells of rats after 24 h following single dose of ADR treatment. ADR treatment caused significant clastogenicity and apoptosis in rat bone marrow cells. The treatment with LA showed significant reduction in the frequency of chromosomal aberrations, DNA strand breaks and apoptosis in bone marrow cells as well as decreased the micronuclei formation in bone marrow and peripheral blood of rats treated with ADR. The protective effect of LA was found to be stronger at a dose of 200 mg/kg body weight than 100 mg/kg body weight dosage with respect to the above results, indicating the dose dependent effect of LA. However, the protection by LA was not dependent on the time intervals between LA and ADR administration. The results of this study illustrate the protective effect of LA on ADR-induced clastogenicity and apoptosis in the erythropoietic system of rats.

Animals↗
PubMed2004

Analysis of proteome and transcriptome of tumor necrosis factor alpha stimulated vascular smooth muscle cells with or without alpha lipoic acid.

Vascular smooth muscle cells (VSMCs) play an important role in the development and progression of atherosclerosis. Tumor necrosis factor alpha (TNFalpha), a cytokine secreted by VSMCs and macrophages in atherosclerotic lesions, regulates a variety of cellular functions of inflammatory cells and VSMCs by promoting cell growth and motility, which are critical for the initiation and progression of vascularlesions. Alpha lipoic acid (ALA), a well known antioxidant, acts as a pyruvate dehydrogenase cofactor in mitochondrial metabolism. Recently, we reported that ALA has many beneficial effects on vascular cells in atherosclerosis. The aim of the current study was to examine VSMCs, treated for 24 hours with TNFalpha (10 ng/mL) in the presence or absence of ALA (2 mM), for differential protein and genes expression using two-dimensional gel electrophoresis (2-DE) and DNA microarray analysis, respectively. Using 2-DE, we identified proteins whose expression changed by at least 2.5-fold after TNFalpha stimulation. Proteins up-regulated by TNFalpha that were subsequently down-regulated in the presence of ALA were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry as plasminogen activator inhibitor-2, fetal liver LKB-interacting protein, osteoblast-specific factor 2, glucosidase II, cyclin-dependent kinase 3, endoplasmin precursor and glutathione synthetase. TNFalpha down-regulated proteins that were up-regulated in the presence of ALA were keratin 19, eukaryotic translation elongation factor and Rho GDP dissociation inhibitor alpha. Gene expression analysis using DNA microarray tools confirmed the up-regulation or down-regulation of some, but not all, of the proteins observed in ALA challenged, TNFalpha-treated cells. This data should provide valuable information about the underlying mechanisms of atherosclerosis.

Blotting, Western↗
PubMed2006

Beneficial effect of supplemental lipoic acid on diabetes-induced pregnancy loss in the mouse.

Uncontrolled diabetes mellitus (DM) is an etiological factor for recurrent pregnancy loss, fetal growth disorders, and major congenital malformations in the offspring. Antioxidant therapy has been advocated to overcome the oxidant-antioxidant disequilibrium inherent in diabetes. The objective of this article was to evaluate the beneficial effects of alpha-lipoic acid (LA) on fetal outcome in a mouse model of streptozotocin (STZ)-induced DM. Timed pregnant mice were made diabetic by intraperitoneal (IP) injection of a single dose of STZ (200 mg/kg) on gestation day (GD) 2. Diabetic animals were supplemented daily with an IP injection of 15 mg/kg of LA starting on GD 4 and continued through GD 12. Fetuses were examined on GD 18 for malformations and growth restriction. Some diabetic mice injected with Evans blue were examined on GD 3.5 and GD 6.5 to evaluate frequency of implantations. STZ-treated mice had all cardinal signs of DM. LA treatment did not normalize blood glucose levels of DM mice. Rates of pregnancy in saline control, DM, and DM + LA groups were 90%, 28%, and 64%, respectively, indicating that LA promotes pregnancy in DM animals. However, postimplantation resorption showed a threefold increase in the DM + LA group. Rates of intrauterine growth restriction and major congenital malformations were also augmented thus indicating that the interaction between DM and LA has deleterious effects on postimplantation embryos.

Abortion, Spontaneous↗
PubMed2004

[Device laboratory and postmortem parallels in alcoholic hepatitis during combined therapy using thioctic (alpha-lipoic) acid].

The absence of clinical, biochemical, and instrumental signs that characterize the morphological pattern of the liver presents an urgent problem in the diagnosis of alcoholic hepatitis (AH). Sixty-one patients (mean age 41.7 +/- 8.7 years) were examined to study relationships between the histomorphological parameters and laboratory and instrumental findings in patients with AH on combined treatment including alpha-lipoic acid (Berlition). Indirect assessment of the histological activity of the disease may use the parameters of the serum activity of aspartate aminotransferase and gamma-glutamine aminotransferase, the stages of hepatic fibrosis-ultrasound symptoms: the splenic index at the early stages of the disease, the diameter of the splenic vein in moderate and severe fibrosis. The supplementation of Berlition in the combined therapy for AH decreases the severity of fatty hepatocytic dystrophy, hepatic inflammatory and necrotic changes, no increase or a decrease in the stage of fibrotic changes in the liver tissue.

Adipocytes↗
PubMed2001

The antioxidant effect of DL-alpha-lipoic acid on copper-induced acute hepatitis in Long-Evans Cinnamon (LEC) rats.

The Long-Evans Cinnamon (LEC) rats, due to a genetic defect, accumulate excess copper (Cu) in the liver in a manner similar to patients with Wilson's disease and spontaneously develop acute hepatitis with severe jaundice. In this study we examined the protective effect of DL-alpha-Lipoic acid (LA) against acute hepatitis in LEC rats. LA was administered to LEC rats by gavage in doses of 10, 30 and 100 mg/kg five times per week, starting at 8-weeks-old and continuing till 12-weeks-old. Although LA had little effect against the increases in serum transaminase activities, it suppressed the loss of body weight and prevented severe jaundice in a dose-dependent manner. Antioxidant system analyses in liver showed that LA treatment significantly suppressed the inactivations of catalase and glutathione peroxidase, and the induction of heme oxygenase-1, an enzyme which is inducible under oxidative stress. Furthermore, LA showed dose-dependent suppressive effect against increase in nonheme iron contents of both cytosolic and crude mitochondrial fractions in a dose-dependent manner. Although at the highest dose, LA slightly suppressed the accumulation of Cu in crude mitochondrial fraction, it had no effect on the accumulation of Cu in cytosolic fraction. While LA completely suppressed the increase in lipid peroxidation (LPO) in the microsomal fraction at the highest dose, the suppressive effect against LPO in crude mitochondrial fractions was slight. From these results, it is concluded that LA has antioxidant effects at the molecular level against the development of Cu-induced hepatitis in LEC rats. Moreover, mitochondrial oxidative damage might be involved in the development of acute hepatitis in LEC rats.

Acute Disease↗
PubMed2004

alpha-lipoic acid inhibits endotoxin-stimulated expression of iNOS and nitric oxide independent of the heat shock response in RAW 264.7 cells.

The heat shock response protects against sepsis-induced mortality, organ injury, cardiovascular dysfunction, and apoptosis. Several inducers of the heat shock response, such as hyperthermia, sodium arsenite, and pyrollidine dithiocarbonate, inhibit NF-kappaB activation and nitric oxide formation. The antioxidant lipoic acid (LA) has recently been found to inhibit NF-kappaB activation and nitric oxide formation. We therefore tested the hypothesis that LA induces a heat shock response. To test this hypothesis, we determined whether exposure to LA affects expression of both heat shock protein 70 (HSP-70) and nuclear heat shock factor-1 (HSF-1) in lipopolysaccharide (LPS) stimulated macrophages. LA and hyperthermia attenuated LPS-induced increases in nuclear NF-kappaB, iNOS protein, and media nitrite concentrations. LPS and hyperthermia increased HSP-70 concentrations 8-fold and 20-fold, respectively. No effect of LA treatment alone on HSP-70 protein expression was detected. Likewise, no effect of LA on HSF-1 protein expression was detected. These data suggest that LA inhibits LPS-induced activation of iNOS in macrophages independent of the heat shock response.

Animals↗
PubMed2006

Alpha-lipoic acid exhibits anti-amyloidogenicity for beta-amyloid fibrils in vitro.

Inhibition of the formation of beta-amyloid fibrils (fAbeta), as well as the destabilization of preformed fAbeta in the CNS would be attractive therapeutic targets for the treatment of Alzheimer's disease (AD). Using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies, we examined the effects of alpha-lipoic acid (LA) and the metabolic product of LA, dihydrolipoic acid (DHLA), on the formation, extension, and destabilization of fAbeta at pH 7.5 at 37 degrees C in vitro. LA and DHLA dose-dependently inhibited fAbeta formation from amyloid beta-protein, as well as their extension. Moreover, they destabilized preformed fAbetas. LA and DHLA could be key molecules for the development of therapeutics for AD.

Amyloid↗
PubMed2004

Alpha-Ketoglutarate dehydrogenase and lipoic acid synthase are important for the functioning of peroxisomes of Saccharomyces cerevisiae.

A method was devised to search for yeast mutants impaired in peroxisome functioning, indicating cross-talk between metabolic pathways. Two mutants were isolated; they are impaired in oleate utilisation and carry mutations in the KGD1 and LIP5 genes encoding the E1 component of the mitochondrial alpha-ketoglutarate dehydrogenase complex and lipoic acid synthase, respectively. The results presented indicate that the Kgd1 and Lip5 proteins are important for the expression of genes encoding peroxisomal matrix proteins, although they are not necessary for the biogenesis of this cellular compartment.

Acyl-CoA Oxidase↗
PubMed2000

Effects of DL-alpha-lipoic acid on peripheral nerve conduction, blood flow, energy metabolism, and oxidative stress in experimental diabetic neuropathy.

Experimental diabetic peripheral neuropathy (DPN) is marked by impaired nerve conduction velocity (NCV), reduced nerve blood flow (NBF), and a variety of metabolic abnormalities in peripheral nerve that have been variously ascribed to hyperglycemia, abnormal fatty acid metabolism, ischemic hypoxia, and/or oxidative stress. Some investigators propose that NCV slowing in experimental DPN can be explained entirely on the basis of nerve energy depletion secondary to reduced NBF. This article reports highly selective effects of administration of the antioxidant DL-alpha-lipoic acid (LA) to streptozotocin-injected diabetic rats. LA improved digital sensory but not sciatic-tibial motor NCV, corrected endoneurial nutritive but not composite NBF, increased the mitochondrial oxidative state without correcting nerve energy depletion, and enhanced the accumulation of polyol pathway intermediates without worsening myo-inositol or taurine depletion. These studies implicate oxidative stress as an important pathophysiological factor in experimental DPN. They reveal complex interrelationships among nerve perfusion, energy metabolism, osmolyte content, conduction velocity, and oxidative stress that may reflect the heterogeneous and compartmentalized composition of peripheral nerve.

Animals↗
PubMed2002

Elimination of *O(2)(-)/H(2)O(2) by alpha-lipoic acid mediates the recovery of basal EDRF/NO availability and the reversal of superoxide dismutase-induced relaxation in diabetic rat aorta.

AIM: The aims of this study were to ascertain the mechanism(s) of relaxant action of exogenous superoxide dismutase (SOD) in aortic rings obtained from 12-week, streptozotocin(STZ)-diabetic and age-matched control rats, and to examine the effects of alpha-lipoic acid (ALA) treatment (for 6 weeks, after 6 weeks of untreated diabetes) on SOD-induced relaxations. MATERIALS AND METHODS: Thoracic aorta rings were suspended to isolated tissue chamber, and the changes in isometric tension were recorded. RESULTS: SOD produced a greater relaxation in untreated-diabetic rings compared with control rings. ALA treatment partially reversed SOD-induced relaxation in diabetic aorta. Pretreatment of rings with N(G)-nitro-L-arginine methyl ester (L-NAME, 100 microm) inhibited SOD-induced relaxation. This effect of L-NAME was markedly observed in control and ALA-treated-diabetic rings compared with untreated-diabetic rings. SOD-induced relaxation was also inhibited by catalase (60 U/ml) in untreated-diabetic rings but not in ALA-treated-diabetic and control rings. Pretreatment with the cyclooxygenase inhibitor, indomethacin, or the catalase inhibitor, aminotriazole, had no effect on SOD-induced relaxation in any ring. CONCLUSION: Findings suggested that: (i) in normal physiological conditions, the relaxant effect of SOD is related to the inhibition of superoxide anion radicals (*O(2)(-))-induced endothelium-derived relaxing factor/nitric oxide (EDRF/NO) destruction in the rat aorta; (ii) in diabetic state, excess *O(2)(-) increasingly inhibits basal EDRF/NO, and the dismutation of excess *O(2)(-) to H(2)O(2) is enhanced by exogenous SOD. H(2)O(2) a vasorelaxant molecule, which probably accounts for the increased responsiveness of diabetic rings to exogenous SOD; and (iii) the reversal effect of in vivo ALA treatment on SOD-induced relaxation in diabetic aorta is probably linked with the elimination of *O(2)(-)/H(2)O(2), which mediates the recovery of basal EDRF/NO availability.

Amitrole↗