Development of an oral and maxillofacial surgery outcomes system for anesthesia and third molar removal: results of alpha and beta testing.
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Adult↗
Biomedical subjects
M L Hu
Publications and source records attributed to M L Hu.
Induction of oxidative DNA damage in human foreskin fibroblast Hs68 cells by oxidized beta-Carotene and lycopene.
Two recent clinical trials suggest that beta-carotene may be harmful to smokers. In this study we examined the hypothesis that beta-carotene may become toxic when degradation occurs. beta-Carotene (BC) and lycopene (LP) with or without prior heat treatment (60 degrees C for 1 h in open air) were incubated at 20 and 40 microM with calf thymus DNA or human fibroblasts Hs68 cells. The heat treatment resulted in ca. 80% and 35% bleaching of BC and LP, respectively. When Hs68 cells were incubated with the oxidized beta-carotene (OBC) or oxidized lycopene (OLP) at 37 degrees C for 20 h, cell viability was significantly and dose-dependently decreased whereas cell viability was not affected by BC or LP. Cell death, which was already evident at 4 h after incubation with OBC or OLP, was possibly attributable to apoptosis, as shown by the increased histone-associated DNA fragmentation. However, cell lysis, measured as release of lactate dehydrogenase, also occurred at 4 h after incubation with OBC and OLP, although the extent was relatively small and was greater for OLP than for OBC. When calf thymus DNA was incubated with OBC or OLP at 37 degrees C for 20 h, the 8-hydroxy-2-deoxyguanosine (8-OH-dG) level was significantly and dose-dependently increased by OLP whereas the increase by OBC was only significant at 40 microM. When Hs68 cells were incubated with OBC and OLP for 20 h, both compounds increased the 8-OH-dG level, but the effect was only significant for 40 microM OLP. Comet (single-cell gel electrophoresis) assay of DNA damage in Hs68 cells was determined at 2 h after incubation with OBC or OLP because of its high sensitivity. Both OBC and OLP significantly and dose-dependently increased DNA breakage while BC and LP had no effect. Inclusion of BHT during incubation of cells with 40 microM OBC or OLP partially inhibited (ca. 40%, p < .05) the extent of comet formation. Intriguingly, OBC and OLP neither induce lipid peroxidation in Hs68 cells (measured as thiobarbituric acid-reactive substances released into the medium) nor increased the intracellular level of reactive oxygen species. Although it is presently unclear about what degradation products are formed, this study has demonstrated that, when oxidized, BC and LP lead to oxidative damage to both purified DNA and cellular DNA. The results suggest that such damage may contribute to the adverse effects of beta-carotene reported in recent clinical studies and caution that it is important to prevent oxidation of BC and LP for human uses such as in supplemental studies.
8-Hydroxy-2'-Deoxyguanosine↗
DHEA inhibits cell growth and induces apoptosis in BV-2 cells and the effects are inversely associated with glucose concentration in the medium.
Dehydroepiandrosterone (DHEA), a major steroid secreted by the adrenal gland which decreases with age after adolescence, is available as a nutritional supplement. DHEA is known to have antiproliferative effects but the mechanism is unclear. In this study using BV-2 cells, a murine microglial cell line, we investigated the effect of DHEA on cell viability and the interaction between DHEA and glucose concentrations in the medium. We showed that DHEA inhibited cell viability and G6PD activity in a dose-dependent manner and that the effect of DHEA on cell viability was inversely associated with glucose concentrations in the medium, i.e. lowered glucose strongly enhanced the inhibition of cell viability by DHEA. DHEA inhibited cell growth by causing cell cycle arrest primarily in the G0--G1 phase, and the effect was more pronounced at zero glucose (no glucose added, G0) than high glucose (4.5 mg/ml of the medium, G4.5). Glucose deprivation also enhanced apoptosis induced by DHEA. At G4.5, DHEA did not induce formation of DNA ladder until it reached 200 microM. However, at G0, 100 microM DHEA was able to induce apoptosis, as evidenced by the formation of DNA ladder, elevation of histone-associated DNA fragmentation and increase in cells positively stained with annexin V-FITC and annexin V-FITC/propidium iodide. The interactions between DHEA and glucose support the contention that DHEA exerts its antiproliferative effects through alteration of glucose metabolism, possibly by inhibition of G6PD activity leading to decreased supply of ribose-5-phosphate for synthesis of DNA and RNA. Although DHEA is only antiproliferative at pharmacological levels, our results indicate that its antiproliferative effect can be enhanced by limiting the supply of glucose such as by energy restriction. In addition, the present study shows that glucose concentration is an important factor to consider when studying the antiproliferative and toxicological effects of DHEA.
Animals↗
Total plasma malondialdehyde levels in 16 Taiwanese college students determined by various thiobarbituric acid tests and an improved high-performance liquid chromatography-based method.
OBJECTIVES: In determining the plasma malondialdehyde MDA levels in some Taiwanese college students, we found rather different results by using different thiobarbituric acid TBA tests, even by the high-performance liquid chromatography HPLC-based methods. Here, we re-evaluated four commonly used TBA tests and improved the HPLC-based test. DESIGN AND METHODS: We used the blood plasma of 16 college volunteers to determine plasma MDA by using four methods: a spectrophotometric measurement of thiobarbituric acid-reactive substances (TBARS) in the TCA-supernatant of plasma (Method A); a fluorescence measurement of plasma lipid peroxides (Method B); and two different HPLC-based measurements of MDA with either 532-nm measurement (Method C, HPLC/532 nm) or fluorescence measurement (Method D, HPLC/fluor.). RESULTS: The levels of MDA or TBA reactive substances obtained from the four methods differed substantially (0.39 +/- 0.15; 2.14 +/- 0.73; 0.75 +/- 0.22; and 0.38 +/- 0.15 microM for Methods A, B, C, and D, respectively). The results were positively correlated between Methods A and B (r = 0.740, p < 0.02) and between Methods C and D (r = 0.516, p < 0.05). However, results were negatively correlated between Methods B and D (r = -0.548, p < 0.05). Because most plasma MDA is bound to proteins, we modified the HPLC-based methods (C and D) by adding an alkaline hydrolysis step, and the plasma TBA-MDA adduct detected by HPLC/532 nm was referred to as total MDA. RESULTS show that alkaline hydrolysis was a critical step for measurement of total MDA in plasma because this treatment led to release of MDA from plasma proteins. We also adapted the potassium iodide (KI) treatment of plasma from Method D to reduce lipid hydroperoxides. Our modified method gave a total MDA level in the 16 volunteers of approximately 1.5 microM, which was equal to protein-bound MDA plus free MDA. This total MDA level was positively (p < 0.05) correlated with the level of TBA reactive substances obtained from Methods C (r = 0.63, p < 0.05) and D (r = 0.48, p < 0.07), but was not correlated with those from Methods A and B. The recovery (84 approximately 105%), precision (within-assay coefficient of variation: 2.4%, between-assay coefficient of variation: 4 approximately 8%) and sensitivity of the modified procedure were comparable to other HPLC-based methods. CONCLUSION: By using a validated modification of HPLC-based TBA method, the total plasma MDA in 16 Taiwanese college students was found to be 1.54 microM, which was relatively high compared to those obtained by other HPLC-based method, primarily due to the release of protein-bound MDA by alkaline hydrolysis. This level equaled the sum of protein-bound MDA and free MDA in plasma, confirming that this level represents total plasma MDA.
Adult↗
Outcomes research: a mandate for oral and maxillofacial surgery (Part I).
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Decision Support Techniques↗
Use of rat liver slices for the study of oxidative DNA damage in comparison with isolated rat liver nuclei and HepG2 human hepatoma cells.
Tissue slices are a useful biological system for lipid peroxidation studies but their use for DNA damage studies is not well characterized. Hence, the present study investigates DNA damage in rat liver slices, in comparison with isolated rat liver nuclei and HepG2 human hepatoma cells, incubated with ferric nitrilotriacetate (Fe(III)-NTA), bromotrichloromethane (BrCCl(3)), bromobenzene (BrB) or 2-nitropropane (2-NP) at 37 degrees C for 2 hr. DNA damage was measured in slices, cells or nuclei after centrifugation as formation of as 8-hydroxy-2'-deoxyguanosine (8-OH-dGu) and loss of double-stranded (dsDNA) due to strand breakage using a fluorometric analysis of DNA unwinding (FADU). Lipid peroxidation was measured as thiobarbituric acid-reactive substances (TBARS) released into the medium. The results show that in liver slices and isolated nuclei, Fe/NTA (1 mM/4 mM) induced high levels of TBARS but low levels of 8-OH-dGu, whereas the oxidant induced low levels of TBARS and no formation of 8-OH-dGu in HepG2 cells. In all three systems, inclusion of ascorbate caused dose-dependent formation of 8-OH-dGu, and the levels were similar between liver slices and HepG2 cells but were far higher in isolated nuclei. In liver slices the FADU assay was not applicable due to limited solubilization of DNA from the slice, whereas the assay detected significant loss of dsDNA in HepG2 cells and slight loss in isolated nuclei induced by Fe/NTA with or without ascorbate. Liver slices incubated with 1 mm BrCCl(3), BrB or 2-NP had elevated TBARS but had little or no formation of 8-OH-dGu; none of these oxidants induced lipid peroxidation or DNA damage in HepG2 cells. When liver slices obtained from rats injected with diethylmaleate (to deplete GSH) were incubated with BrCCl(3), BrB or 2-NP, levels of TBARS and 8-OH-dGu increased markedly. Similarly, HepG2 cells with decreased GSH showed marked elevation of TBARS and loss of dsDNA induced by these oxidants, although no formation of 8-OH-dGu was detected. The present study demonstrates the usefulness and limitations of liver slices for DNA damage studies and the importance of cellular GSH in the protection of DNA against environmental toxicants.
8-Hydroxy-2'-Deoxyguanosine↗
UVA-induced oxidative damage to rat liver nuclei: reduction of iron ions and the relationship between lipid peroxidation and DNA damage.
Lipid peroxidation and DNA damage and the relationship between the two events were studied in rat liver nuclei irradiated with low dose UVA. Lipid peroxidation was measured as thiobarbituric acid-reactive substances (TBARS) by spectrophotometric method and as malondialdehyde-TBA adduct by HPLC, and DNA damage was measured as 8-hydroxy-deoxyguanosine (8-OH-dGu) and strand breakage (or loss of double-stranded DNA) by a fluorometric analysis of alkaline DNA unwinding method. The results show that UVA irradiation by itself increased nuclear lipid peroxidation but caused little or no DNA strand breakage or 8-OH-dGu. When 0.5 mM ferric (Fe+3) or ferrous (Fe+2) ions were added to the nuclei during UVA irradiation, lipid peroxidation and DNA damage, measured both as 8-OH-dGu and loss of double-stranded DNA, were strongly enhanced. Lipid peroxidation occurred concurrently with the appearance of 8-OH-dGu. Fe3+ ions were reduced to Fe2+ in this UVA/Fe2+/nuclei system. Lipid peroxidation and DNA damage were neither inhibited by scavengers of hydroxyl radical and singlet oxygen nor inhibited by superoxide dismutase and catalase. Inclusion of EDTA or chain-breaking antioxidants, butylated hydroxytoluene (BHT) and diphenylamine (an alkoxy radical scavenger), inhibited lipid peroxidation but not the level of 8-OH-dGu. BHT also did not inhibit the loss of double-stranded DNA in this system. This study demonstrates the reduction of exogenous Fe+3 by UVA when added to rat liver nuclei, and, as a result, oxidative damage is strongly enhanced. In addition, the results show that DNA damage is not a result of lipid peroxidation in this UVA/Fe2+/nuclei system.
Animals↗
Elevated lipid peroxidation and disturbed antioxidant enzyme activities in plasma and erythrocytes of patients with uterine cervicitis and myoma.
OBJECTIVES: We investigated whether oxidative stress is associated with human uterine cervicitis and uterine myoma. DESIGN AND METHODS: We measured lipid peroxidation and antioxidant enzymes in plasma and erythrocytes of cervicitis patients and myoma patients in comparison with matched controls. Thiobarbituric acid-reactive substances (TBARS), a measure of lipid peroxidation, were determined in plasma; glutathione peroxidase (GSHPx) and catalase in erythrocytes; and superoxide dismutase (SOD) in both plasma and erythrocytes. RESULTS: We showed that plasma TBARS were significantly higher (p < 0.05) in both cervicitis patients and myoma patients than in controls. Plasma TBARS were significantly (and negatively) correlated with plasma and erythrocyte T-SOD activities in cervicitis patients only. Plasma T-SOD activity was significantly lower in both groups of patients than in controls whereas erythrocyte T-SOD activity was only significantly lower in myoma patients. The lowered plasma T-SOD activity in the cervicitis patients was attributed to decreased Mn-SOD activity whereas the lowered plasma T-SOD activity in myoma patients was attributed to decreased activities of both Cu,Zn-SOD and Mn-SOD. Erythrocyte GSHPx activity was 14% higher (p < 0.05) in cervicitis patients and 11% lower (p > 0.05) in myoma patients than in controls; catalase activity was 10% higher (p > 0.05) in cervicitis patients and 13% lower (p > 0.05) in myoma patients than in controls. Neither erythrocyte GSHPx nor catalase activity was significantly correlated with plasma TBARS. CONCLUSIONS: The elevated lipid peroxidation and disturbed antioxidant enzyme activities demonstrate the potential of oxidative injury in patients with uterine cervicitis and myoma.
Adult↗
Toxicological and antioxidant effects of short-term dehydroepiandrosterone injection in young rats fed diets deficient or adequate in vitamin E.
This study examined the in vivo antioxidant and/or prooxidant effect of short-term dehydroepiandrosterone (DHEA) injection and the effect of dietary vitamin E. Male Sprague-Dawley rats (4 wk old) were fed vitamin E-deficient or vitamin E-adequate (30 mg DL-alpha-tocopheryl acetate/kg) diet for 4 weeks followed by intraperitoneal injection of DHEA for 1 week. The results showed that DHEA injection caused a dose-dependent decrease in body weight, and this effect was more pronounced in vitamin E-deficient rats. In contrast, DHEA injection significantly increased liver, kidney and adrenal weights. Hepatic vitamin E content was significantly lowered by vitamin E deficiency, which led to significantly increased ex vivo and iron-induced lipid peroxidation. DHEA injection did not affect hepatic vitamin E content but significantly decreased ex vivo and iron-induced lipid peroxidation in vitamin E-deficient rats. Hepatic total sulfhydryl (SH) groups and non-protein SH contents were not affected by vitamin E but were significantly increased by DHEA injection, which at 100 mg/kg was not more effective than at 50 mg/kg. Hepatic glutathione S-transferase (GST) activity was significantly decreased by DHEA, but vitamin E alleviated such a decrease. DHEA injection significantly increased hepatic glucose 6-phosphate dehydrogenase (G6PD) activity, and the effect was dose dependent in vitamin E-deficient rats. Thus, DHEA may compensate for vitamin E deficiency in vivo, and this effect is masked when dietary vitamin E is adequate. The antioxidant effect of DHEA is accompanied by decreased body weights, enlarged (fat-laden) tissues and altered activities of hepatic GST and G6PD.
Analysis of Variance↗
Plasma levels of antioxidant vitamins, selenium, total sulfhydryl groups and oxidative products in ischemic-stroke patients as compared to matched controls in Taiwan.
The possible involvement of oxidative damage and antioxidant protection has been suggested in the pathogenesis of stroke which is the second-leading cause of death in Taiwan. In this study we investigated the relationship between ischemic stroke and plasma status of antioxidants and oxidative products. Plasma levels of vitamin A, alpha-tocopherol, carotenoids, selenium (Se), total SH groups (T-SH), thiobarbituric acid-reactive substances (TBARS) and protein carbonyl, a marker of protein damage, were determined in ischemic-stroke patients (n = 36, blood sampled within 24 hrs after the clinical event) in comparison with 21 matched controls. The cholesterol-adjusted carotenoids and vitamin E were significantly lower (P < 0.05) in the plasma of ischemic-stroke patients than those of the controls. TBARS were higher (P < 0.05) in the patients than in the controls but Se, T-SH and protein carbonyls were not significantly different between the two groups. Separation of the patients into small-artery ischemic stroke (SAIS, n = 17) and large-artery ischemic stroke (LAIS, n = 19) groups revealed that both carotenoids/cholesterol and vitamin E/cholesterol ratios were significantly lower in both LAIS and SAIS groups than the controls (n = 21) while vitamin A/cholesterol was not different among the three groups. TBARS were only significantly higher in the LAIS group. The results demonstrated that, within 24 hrs after the clinical event, the acute-ischemic stroke patients had lowered levels of cholesterol-adjusted carotenoids and alpha-tocopherol but elevated levels of TBARS in the plasma as compared to the matched controls. It remains to be resolved as to whether enhanced lipid peroxidation is a cause or a result of lowered antioxidants in ischemic stroke.
Adult↗
Hemolytic effects of dehydroepiandrosterone in vitro.
Dehydroepiandrosterone (DHEA), a major steroid secreted by the adrenal gland which decreases with age after adolescence, is available as a over-the-counter product. This study demonstrates that DHEA induced lysis of human red blood cells (RBCs) in a concentration-dependent manner, with ca. 70% hemolysis at 2 mM DHEA at 37 degrees C for 1 hr. Hemolysis induced by 2 mM DHEA was rapid and involved neither hemoglobin oxidation nor lipid peroxidation. The hemolysis was also not inhibited by addition of EDTA, catalase, superoxide dismutase, glucose or a radical scavenger including mannitol, dimethylsulfoxide and alpha-tocopherol, indicating a non-oxidative mechanism. RBCs stored overnight before incubation with DHEA were hemolyzed to a lesser extent than the freshly prepared RBCs. Light microscopy of the fresh RBCs following 1-h incubation with 2 mM DHEA revealed thickened and cup-shaped deformity of the membranes, suggesting a change in the membrane structure possibly due to the intercalation of the steroid into the membranes.
Dehydroepiandrosterone↗
Nutritional evaluation of women in urban areas in continental China.
In 1993-1995, a nutritional survey was conducted in China, in which 50 women each in three cities of Beijing, Shanghai and Nanning (thus 150 in total) volunteered to offer 24-hr total food duplicates and peripheral blood samples. People daily took 1,776 kcal (7,431 kJ) energy, 57 g protein, 75 g lipid, 218 g carbohydrate, 439 mg calcium, 24 mg iron, 3,398 mg sodium and 1,521 mg potassium. When compared with the recommended dietary allowance for Chinese, intakes of energy, iron and possibly vitamin C were sufficient in a majority of the participants, but not so in cases of calcium, and several vitamins. The lipid energy ratio was 38% on an average and was higher than 30% in a majority (73%) of the people. BMI, but not the lipid energy ratio, correlated with the serum triglyceride level. In accordance with high iron intake, the prevalence of anemia was low. Inter-city differences were evident in nutrient sources. Thus, Beijing people took more amounts of protein and lipid from meats (including eggs and milk), whereas plant-based foods were important sources of lipid in Shanghai and that of protein in Nanning. Furthermore, consumption of rice was significantly lower in Beijing than in Shanghai and Nanning, whereas wheat consumption was higher in Beijing than in Shanghai and Nanning.
Adult↗
Ascorbic acid inhibits lipid peroxidation but enhances DNA damage in rat liver nuclei incubated with iron ions.
In this report we studied DNA damage and lipid peroxidation in rat liver nuclei incubated with iron ions for up to 2 hrs in order to examine whether nuclear DNA damage was dependent on membrane lipid peroxidation. Lipid peroxidation was measured as thiobarbituric acid-reactive substances (TBARS) and DNA damage was measured as 8-OH-deoxyguanosine (8-OH-dG). We showed that Fe(II) induced nuclear lipid peroxidation dose-dependently but only the highest concentration (1.0 mM) used induced appreciable 8-OH-dG. Fe(III) up to 1 mM induced minimal lipid peroxidation and negligible amounts of 8-OH-dG. Ascorbic acid enhanced Fe(II)-induced lipid peroxidation at a ratio to Fe(II) of 1:1 but strongly inhibited peroxidation at ratios of 2.5:1 and 5:1. By contrast, ascorbate markedly enhanced DNA damage at all ratios tested and in a concentration-dependent manner. The nuclear DNA damage induced by 1 mM FeSO4/5 mM ascorbic acid was largely inhibited by iron chelators and by dimethylsulphoxide and mannitol, indicating the involvement of OH. Hydrogen peroxide and superoxide anions were also involved, as DNA damage was partially inhibited by catalase and, to a lesser extent, by superoxide dismutase. The chain-breaking antioxidants butylated hydroxytoluene and diphenylamine (an alkoxyl radical scavenger) did not inhibit DNA damage. Hence, this study demonstrated that ascorbic acid enhanced Fe(II)-induced DNA base modification which was not dependent on lipid peroxidation in rat liver nuclei.
8-Hydroxy-2'-Deoxyguanosine↗
UVA-potentiated damage to calf thymus DNA by Fenton reaction system and protection by para-aminobenzoic acid.
Calf thymus DNA was irradiated with low-intensity UVA (main output at 365 nm, 2 mW cm-2 or 36 kJ m-2 for 30 min), and the role of metal ions, hydrogen peroxide and reactive oxygen species (ROS) was examined. DNA damage was measured as thiobarbituric acid-reactive substances (possibly from degradation of deoxyribose) and as changes in ethidium bromide-DNA fluorescence due to unwinding from strand breaks. Under the present experimental conditions, UVA alone or in the presence of H2O2 had no effect on DNA but slightly enhanced the damage by iron/EDTA. Ultraviolet A strongly enhanced DNA damage (ca four- to five-fold) by the Fenton reaction system (50 microM Fe2+/100 microM EDTA + 0.5 mM H2O2). The results suggest that the Fenton reaction system was "photosensitized" to damage DNA by low-intensity UVA radiation. The enhanced damage by UVA was attributed in part to the reduction of Fe3+ to Fe2+. Ultraviolet A had no effect when iron (ferric or ferrous) ions were replaced by Cu2+, Zn2+, Mn2+ or Cd2+. The ROS involved in the UVA-enhanced damage to DNA by the Fenton reagents were OH and, to a lesser extent, superoxide anions. The UVA-potentiated DNA damage by the Fenton reaction system was then used to examine the protective effect of para-aminobenzoate (PABA), a UVB-absorbing sunscreen that protects against photocarcinogenesis in hairless mice. The results show that PABA and mannitol dose-dependently inhibited the damage with concentrations required for 50% inhibition at 0.1 mM and 3 mM, respectively. The protection by PABA was attributed to its radical-scavenging ability because PABA does not absorb light in the UVA region. These findings may be relevant to the biological damage by UVA and suggest that PABA is useful in protection against photocarcinogenesis by wide-range UV radiation.
4-Aminobenzoic Acid↗
The antioxidant and prooxidant activity of some B vitamins and vitamin-like compounds.
The antioxidant and prooxidant properties of some B vitamins (BVIT) and vitamin-like compounds (VLC) that are commonly included in multivitamin preparations were investigated. Microsomal lipid peroxidation induced by FeCl3 and ascorbate was dose-dependently inhibited by pyridoxal and pantothenate but was stimulated by thiamin, pyridoxine and carnitine. Among the compounds tested, only pyridoxine and pyridoxal reacted, but rather poorly, with superoxide anions. All test compounds reacted with .OH with second-order rate constants comparable or higher than that for mannitol, as assayed using deoxyribose oxidation by a system containing EDTA-chelated Fe(III), H2O2 and ascorbate. When assayed in the absence of EDTA, pyridoxal showed increased inhibition of deoxyribose oxidation over that in the presence of EDTA, suggesting a potent ability of pyridoxal to bind and deactivate iron. Pantothenate, pyridoxine and myo-inositol appeared to equally inhibit deoxyribose oxidation both in the presence and absence of EDTA. The lack of inhibition on deoxyribose oxidation in the absence of EDTA by thiamin, carnitine and choline may suggest that the .OH-scavenging ability is equalled by the ability of the scavenger-iron complexes to form .OH or other redox active species. However, stimulation of lipid peroxidation by pyridoxine was unexplained and the effect was not attributed to reduction of Fe(III) to Fe(II). This study shows that the radical-scavenging ability of BVIT and VLC did not correlate with their effects on microsomal lipid peroxidation. Moreover, the stimulation of lipid peroxidation by thiamin, pyridoxine and carnitine suggests that supplementation of large amounts of these compounds may not be desirable.
Animals↗
Some similarities in vascular effects of oleic acid and oxidized low-density lipoproteins on rabbit aorta.
In the present study oxidized low-density lipoproteins (ox-LDL) was prepared by a new simple method: oxidizing LDL by electrolysis-generated free radicals. In endothelium-intact norepinephrine(NE)-precontracted rabbit aortic rings, ox-LDL (2 mg protein/ml)-incubation for 30 min or 3 mM oleic acid for 10 min, significantly attenuated the acetylcholine (ACh)-induced endothelium-dependent relaxation (EDR) (both P < 0.01 v control). Such attenuated EDR were sustained after washout. The oleic acid-induced endothelial dysfunction was associated with concomitant reduction of cGMP level in aortic rings. Preincubation of aortic rings with 500 microM L-arginine or 100 u/ml superoxide dismutase for 10 min partly prevented the oleic acid-induced attenuation of EDR and reduction of cGMP, indicating that oleic acid may impair the L-arginine-nitric acid pathway and/or inactivate the nitric oxide. Both ox-LDL and oleic acid potentiated NE-induced aortic ring contraction (both P < 0.01 v control). Such potentiating effects were abolished by preincubation with 1 microM verapamil, indicating the possible involvement of calcium influx in vascular smooth muscle cells during the enhanced contraction. Gas-chromatographic analysis showed that oleic acid content is the highest among all free fatty acids in ox-LDL. In conclusion, we found that oleic acid possesses certain similar vascular effects as ox-LDL in inducing endothelial dysfunction and in enhancing NE-induced vasocontraction in rabbit aortic ring. We proposed that the vasoactive effects of ox-LDL may be resulted partly from the activation or release of active oleic acid molecule during oxidative modification of LDL.
Acetylcholine↗
Measurement of protein thiol groups and glutathione in plasma.
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Animals↗
Potentiation of oxidative damage to rat red blood cells by the concurrent presence of t-butyl hydroperoxide and bromotrichloromethane.
Recently potentiation of oxidative damage in rat red blood cells (rRBC) incubated with t-butylhydroperoxide (BHP) in combination with bromotrichloromethane (BrCCI3) was demonstrated. The mechanism by which this combination (BrCCI3/BHP) potentiates the oxidative damage to rRBC was investigated in this study. When rRBC were incubated with 0.1 mM BHP, 0.5 mM BrCCI3, or the two combined, BrCCI3/BHP-potentiated lipid peroxidation and hemolysis were further enhanced under anaerobic conditions. However, the potentiation of lipid peroxidation was abolished by heating or trypsin digestion of rRBC. Electron spin resonance (ESR) studies demonstrated an increase of alkoyl radical induced by BrCCI3/BHP in rRBC, and this increase was abolished by heating or predigestion of hemolysates with trypsin. The inhibition of lipid peroxidation by diphenylamine (which reacts with alkoxyl radicals but not peroxyl radicals) suggests an important role of alkoxyl radicals. Overall, the present findings demonstrate that the increase in radical-related oxidative damage, possibly mediated by proteinlike materials, may be at least partially responsible for the potentiation of damage to rRBC induced by BrCCI3/BHP, and perhaps by BrCCI3. Although the in vivo significance of these results remains to be investigated, it seems likely that halocarbon toxicity may be amplified by elevated levels of lipid peroxide in blood.
Animals↗