Possible Role Of Lipid Peroxidation Research Articles

Heavy metals exposure, lipid peroxidation and heart rate variability alteration: Association and mediation analyses in urban adults

Exposure to heavy metals was reported to be associated with heart rate variability (HRV) alteration. However, possible pathway of such association remains unclear. In this research, we investigated the possible role of lipid peroxidation in the associations between urinary heavy metals and HRV. We performed a cross-sectional study using baseline data of Wuhan-Zhuhai cohort. Urinary heavy metals (including lead, barium, antimony, cadmium, zinc, copper, iron and manganese), urinary 8-iso-prostaglandin-F2α levels (common biomarker for lipid peroxidation) and HRV indices (SDNN, r-MSSD, low frequency, high frequency and total power) were measured among 3022 participants. We conducted multivariable linear regression models to quantify associations between urinary 8-iso-prostaglandin-F2α (8-iso-PGF2α) and heavy metals or HRV indices. The potential role of 8-iso-PGF2α in the association of urinary heavy metals with HRV was evaluated through mediation analyses. After adjusting for potential confounders, urinary manganese, iron, copper, zinc, cadmium, antimony and barium were identified to be negatively associated with one or more HRV parameters. Each one-unit growth of log-transformed levels of urinary manganese, iron, copper, zinc, antimony and barium was associated with a 1.9%, 1.5%, 4.7%, 4.0%, 2.7% and 1.3% decrease in SDNN, respectively. We observed positive dose-response relationships between all eight urinary heavy metals and 8-iso-PGF2α, as well as negative association of urinary 8-iso-PGF2α with SDNN and total power (all P trend<0.05). The proportions mediated by 8-iso-PGF2α on SDNN were 4.6% for manganese, 9.3% for iron, 19.8% for antimony and 11.0% for barium. The proportions mediated by 8-iso-PGF2α on total power were 6.9% for manganese and 10.1% for cadmium (all P value < 0.05). This study suggested that urinary manganese, iron, copper, zinc, cadmium, antimony and barium were negatively associated with HRV indices. Lipid peroxidation may partly mediate the associations of urinary manganese, iron, cadmium, antimony and barium with specific HRV indices.

Prophylaxis and therapeutic effects of raspberry (Rubus idaeus) on renal stone formation in Balb/c mice

To evaluate the prophylactic potential of herbal decoction from Rubus idaeus, a medicinal plant widely used in the Middle East to treat kidney stones, by assessing the effect of administration in experimentally induced calcium oxalate (CaOx) nephrolithiasis in mice. This study was based on administration of glyoxylate and/or herbal treatments simultaneously for 12 days, followed by histological and biochemical tests. Group I was used as a negative control. Group II was only given daily intra-abdominal injection of glyoxylate (80 mg/Kg). Group III and IV were given 100 mg/kg/day and 200 mg/kg/day of aqueous extract of R. idaeus by gavage, respectively in addition to glyoxylate injection. To examine the effect of anti-oxidants on hyperoxaluria-induced changes in kidney, the enzymatic and non-enzymatic anti-oxidant levels were assessed. Significant reductions were obtained in the urinary oxalate, calcium and phosphorus values in the herbal-treated groups relative to untreated animals while creatinine excretion increased. Serum oxalate, calcium and creatinine were significantly reduced, while phosphorus was not significantly changed. Kidney content of calcium was higher in the untreated group. Mice in treated groups at 12 days had significantly more superoxide dismutase, catalase, glutathione reductase (GSH) and G6PD activities than the untreated group. Hyperoxaluria-induced generation of malondialdehyde (MDA) and protein carbonyls was significantly prevented in the treated groups. R. idaeus had a significantly high content of vitamin E in the herbal treated groups. The histology showed more CaOx deposition in the kidneys of untreated animals. Rubus idaeus has an impressive prophylactic effect on CaOx stones in nephrolithic mice. There is a possible role of lipid peroxidation in CaOx stone formation which may has a relationship with the major risk factors in urine including oxalate, calcium, phosphorus and MDA. Further experimental studies are required to elucidate the chemical constituents of the active ingredients of this interesting plant.

Increased protein glycation in non-diabetic pediatric nephrotic syndrome: Possible role of lipid peroxidation

Background: Malondialdehyde (MDA), ascorbic acid and reduced glutathione (GSH) have been reported to play a possible role in glycation of proteins. This study was performed to evaluate this correlation in nephrotic syndrome patients by comparing the levels of fructosamine with MDA, ascorbic acid and GSH. Methods: Fifteen children with nephrotic syndrome during relapse and 10 age- and sex-matched healthy controls were enrolled for this study. Whole blood GSH, plasma MDA, total ascorbic acid and fasting glucose were analyzed in both the groups. Partial correlation analysis was performed to predict the independent association of MDA, ascorbic acid and GSH on fructosamine. Results: Plasma MDA and fructosamine levels were found to be increased in nephrotic syndrome patients when compared with controls. Plasma ascorbic acid and whole blood GSH were decreased in nephrotic group vs. healthy controls. Partial correlation analysis showed a significant positive correlation between fructosamine and MDA. Conclusions: Present data point to a possible involvement of MDA in the glycation of protein in non-diabetic nephrotic syndrome patients, and provide support for the potential use of an antioxidant therapy in these patients.

Anti-Malondialdehyde Antibodies in MRL+/+ Mice Treated with Trichloroethene and Dichloroacetyl Chloride: Possible Role of Lipid Peroxidation in Autoimmunity

Trichloroethene (TCE) and one of its metabolites dichloroacetyl chloride (DCAC) are known to induce/accelerate autoimmune (AI) response in MRL+/+ mice as evident from anti-nuclear, anti-ssDNA, anti-cardiolipin, and DCAC-specific antibodies in the serum (Khan et al., Toxicol. Appl. Pharmacol. 134, 155–160, 1995). In the present study, we measured anti-malondialdehyde antibodies (AMDA) in the serum of TCE- or DCAC-treated mice in order to understand the contribution of lipid peroxidation to this AI response. Female MRL+/+ mice (5 weeks old) received ip injections of 10 mmol/kg TCE or 0.2 mmol/kg of DCAC in corn oil (100 μl) every 4th day for 6 weeks, while controls received an equal volume of vehicle only, and AMDA was measured in the sera of these animals by an ELISA established in our laboratory. While TCE treatment caused only marginal induction of AMDA, DCAC treatment elicited a significant AMDA response. Furthermore, a time–response study of DCAC (0.2 mmol/kg, every 4th day, for 2, 4, 6, or 8 weeks) showed an induction of AMDA (3/4) after 4 weeks of treatment, which was even greater at both 6 and 8 weeks of DCAC treatment (5/5). These findings were further substantiated by the presence of AMDA in systemic lupus erythematosus-prone MRL-lpr/lpr mice as early as 6 weeks of age. Presence of AMDA, as observed in this study, not only indicates increased lipid peroxidation (oxidative stress), but also suggests a putative role of oxidative stress in inflammatory autoimmune diseases.

Possible role of lipid peroxidation in the induction of NF-kappa B and AP-1 in RFL-6 cells by crocidolite asbestos: evidence following protection by vitamin E.

Asbestos fibers cause persistent induction of the oxidative stress sensitive transcription factors nuclear factor kappa-B (NF-kappa B) and activator protein-1 (AP-1) in mammalian cells. These transcription factors play an important role in the regulation of cellular activity. Lipid peroxidation, mediated by reactive oxygen species, is thought to be a possible mechanism in the pathogenicity of asbestos fibers. These studies were designed to determine if crocidolite asbestos-induced lipid peroxidation plays a role in the mechanism of formation of NF-kappa B and AP-1. Treatment of a rat lung fibroblast cell line (RFL-6) with crocidolite asbestos in the presence and absence of the membrane antioxidant vitamin E decreased the levels of crocidolite-induced AP-1 and NF-kappa B to background levels. Preincubation of RFL-6 cells with 5,8,11,14-eicosatetraynoic acid, an inhibitor of arachidonic acid metabolism, prior to exposure to crocidolite, abrogated crocidolite-induced NF-kappa B DNA-binding activity to background levels. Coincubation with indomethacin, a cyclooxygenase inhibitor, had no effect on NF-kappa B DNA-binding activity induced by crocidolite. However, nordihydroguaiaretic acid, a lipoxygenase inhibitor, decreased levels of NF-kappa B to background levels. This would suggest that lipoxygenase metabolites of arachidonic acid, produced following lipid peroxidation, are involved in the cellular signalling events to NF-kappa B transcription factor induction by asbestos.

Possible Role of Lipid Peroxidation in the Induction of NF-kB and AP-1 in RFL-6 Cells by Crocidolite Asbestos: Evidence Following Protection by Vitamin E

Possible Role of Lipid Peroxidation in the Induction of NF-kB and AP-1 in RFL-6 Cells by Crocidolite Asbestos: Evidence Following Protection by Vitamin E

Lipid peroxidation and peroxide‐scavenging in soybean seeds during aging

The possible role of lipid peroxidation in seed deterioration was investigated during natural aging and accelerated aging of seeds of edible soybean (Glycine max [L], Merr. cv. Kaohsiung Selection No. 1). Natural aging was achieved by sealing the seeds in aluminum foil bags coated with polyethylene and storing the seeds at room temperature for 3 to 12 months. Accelerated aging was obtained by incubating the seeds at 45°C and close to 100% relative humidity for 3 to 12 days, after which the seeds were air dried to their original moisture level (8%). The results indicate that both natural and accelerated aging enhanced lipid peroxidation, as germination was depressed. Aging also inhibited the activity of superoxide dismutase, catalase, ascorbate peroxidase and peroxidase. The changes in germination and physiological activities, expressed as a function of aging duration, were somewhat similar in the two aging treatments.

Protection of cultured rat gastric cells against oxidant stress by iron chelation

Reactive oxygen metabolites may be involved in the pathogenesis of ethanol-, nonsteroidal antiinflammatory drug-, Helicobacter pylori-, or ischemia/reoxygenation-induced gastric mucosal injury in vivo. Iron plays a critical role in mediating oxidant injury in vitro. The present study examined a possible role of lipid peroxidation in inducing oxidant damage by determining the effect of iron chelation on cytotoxicity and on lipid peroxidation in cultured rat gastric cells. Cytotoxicity was quantified by 51Cr release from prelabeled cells that were exposed to tert-butyl hydroperoxide (tBHP) so as to overwhelm the glutathione redox cycle. Lipid peroxidation was assessed by measuring malondialdehyde (MDA) production. tBHP caused a time-related and dose-dependent increase of 51Cr release. The presence of phenanthroline (a chelator of Fe2+) during tBHP exposure and pretreatment with deferoxamine (a chelator of Fe3+) reduced tBHP-induced 51Cr release dose dependently. The generation of MDA increased as the concentrations of tBHP increased, but in a time course study, such generation preceded cytolysis. Both iron chelators attenuated MDA production in a dose-dependent fashion. Oxidant stress causes lipid peroxidation in cultured gastric cells, which is then followed by cytolysis. Iron plays a critical role in inducing lipid peroxidation as well as in mediating cytolysis. Iron chelation protects these cells from oxidant stress presumably through inhibition of lipid peroxidation.

Lipid peroxidation, low-level chemiluminescence and regulation of secretion in the mammary gland.

In mammary explants of lactating mice, changes in the intensity of chemiluminescence (CL) were observed after the addition to the incubation medium of hormones and mediators that are involved in the regulation of secretion: oxytocin, acetylcholine, epinephrine and norepinephrine. A 15-min period of treatment with oxytocin, epinephrine or norepinephrine changed the level of thiobarbituric acid-reactive substances (TBARS). Two mammary explants, one of which was treated with oxytocin, acetylcholine, epinephrine or norepinephrine, were found to interact even when separated by a quartz glass wall. Analysis of the level of TBARS formation in these two explants showed that the observed interactions might be connected with light emission resulting from lipid peroxidation (LP) processes. The possible role of LP and low-level CL in the regulation of mammary gland secretion is discussed.

Role of membrane lipid composition in the cytotoxicity of the sesquiterpene lactone eupatoriopicrin

AbstractThe aim of the present study was to investigate a possible role of lipid peroxidation in the cytotoxicity of eupatoriopicrin, the principal sesquiterpene lactone from Eupatorum cannabinum L. Incorporation of arachidonic acid acyl chains in the phospholipids of cellular membranes of mouse fibroblast LM cells enhanced their sensitivity to the cytotoxic effect of eupatoriopicrin. In the clonogenic assay (2 h exposure) 90% cell kill was found with 14.4 μM eupatoriopicrin in normal cells and 11.7 μM in cells enriched with arachidonic acid (PUFA cells). After incubation with eupatoriopicrin a more rapid loss of membrane integrity and more lysis was found for PUFA cells in the trypan blue exclusion assay. Using gas chromatography, it was shown that the spectrum of fatty acid acyl chains in the phospholipids of normal cells remained unchanged after 2 h incubation with 20 μM eupatoripicrin, followed by 24 h post‐incubation. In PUFA cells the polyunsaturated fatty acids were found to degrade possibly due to lipid peroxidation. Using the alkaline unwinding assay and clamped homogeneous electric field electrophoresis, more DNA damage was found in PUFA cells than in normal cells after treatment with eupatoriopicrin. However, because in normal cells, in which PUFA were nearly absent, DNA damage was found as well, it is concluded that lipid peroxidation plays at most a minor role in eupatoriopicrin‐induced cell killing.

The role of lipid peroxidation in the nephrotoxicity of cisplatin

The possible role of lipid peroxidation in the nephrotoxicity of the antitumour drug cisplatin was studied in vitro. In contrast to Adriamycin ®, cisplatin did not induce lipid peroxidation in rat kidney microsomes containing a NADPH-generating system. Pretreatment of rat kidney microsomes with cisplatin did not reduce the activity of a microsomal glutathione (GSH)-dependent protective factor against lipid peroxidation induced by Fe 2+-ascorbate. However, pretreatment of rat kidney microsomes with 0.1 mM N-ethyl maleimide (NEM) did reduce this GSH-dependent protection. Cisplatin also did not reduce the activity of a cytosolic GSH-dependent protective factor against Fe 2+-ascorbate-induced lipid peroxidation. The results of our experiments indicate that, in contrast to Adriamyci, cisplatin does not induce lipid peroxidation in vitro in various test systems. It also does not destroy microsomal and cytosolic GSH-dependent protective factors against lipid peroxidation.

Endrin-induced increases in hepatic lipid peroxidation, membrane microviscosity, and DNA damage in rats.

Endrin is a polyhalogenated cyclic hydrocarbon pesticide which produces hepatic and neurologic toxicity. Previous studies have indicated that endrin induces hepatic lipid peroxidation. In order to further assess the possible role of lipid peroxidation in the toxicity of endrin, the dose- and time-dependent effects of endrin on hepatic lipid peroxidation, membrane microviscosity and DNA damage in rats were examined. Rats were treated with 0, 3.0, 4.5, or 6.0 mg endrin/kg as a single oral dose in corn oil, and the animals were killed 0, 12, 24, 48, or 72 h post-treatment. Dose-dependent increases in hepatic mitochondrial and microsomal lipid peroxidation and microviscosity as well as nuclear DNA single strand breaks were observed as early as 12 h post-treatment. Maximum increases in these three parameters occurred 24 h after endrin administration at all three doses. While the incidence in DNA damage decreased with time after 24 h, the incidence of lipid peroxidation and microviscosity of microsomal and mitochondrial membranes remained relatively constant. Dose- and time-dependent increases in liver and spleen weight/body weight ratios with decreases in thymus weight/body weight ratios were observed. The data indicate that endrin administration induces hepatic lipid peroxidation which may be responsible for the increased membrane microviscosity as a result of membrane damage as well as enhanced DNA damage.

Hyperbilirubinemia after esophagectomy. A possible role of lipid peroxidation.

Postoperative hyperbilirubinemia was investigated in 18 patients who underwent a single-staged esophagectomy and reconstruction. The total serum bilirubin (TSB) concentration increased progressively after surgery without any evidence of sepsis and reached a peak on day 5 from 0.5 +/- 0.1 to 2.4 +/- 0.4 mg/dl (p less than 0.01), and then decreased by day 14. The TSB concentration rose above 2.5 mg/dl on days 5 or 7 in 8 patients (44%). Alkaline phosphatase and SGOT showed a mild increase during the postoperative period. The increase in the serum lipid peroxide (LPO) concentration, which was measured as malondialdehyde, after surgery correlated closely with the change in the TSB concentration. The LPO concentration was significantly elevated only in the patients with postoperative hyperbilirubinemia, and showed a correlation with the TSB concentration (r = 0.81, p less than 0.01). The level of serum alpha-tocopherol decreased after surgery, but did not differ between the patients with or without postoperative hyperbilirubinemia. These results suggest that lipid peroxidation reactions play a role in the development of hyperbilirubinemia after esophagectomy, which may be due to benign intrahepatic cholestasis.

Lipid peroxidation of liposome induced by glucosone.

Lipid peroxidation of liposome made of egg lecithin was induced by glucosone (D-arabino-hexos-2-ulose), a secondary product of Maillard reaction or glycation of protein. Lipid peroxidation was assessed with measurement of TBARS (thiobarbituric acid reacting substances), POV (peroxide value), and HPLC measurement of MDA (malondialdehyde). EDTA and DTPA (diethylenetriamine-pentaacetic acid) inhibited the lipid peroxidation assessed by each method described above, indicating involvement of metal ions. The observed reduction of Fe3+ to Fe2+ by glucosone might be a critical step of the lipid peroxidation. Our findings suggest a possible role of lipid peroxidation of low-density lipoproteins (LDL) induced by glucosone in atherosis caused by diabetes mellitus.

Fatty acid oxidation and myocardial phospholipase A2 activity

Cis-unsaturated fatty acids, but not saturated fatty acids, inhibited phospholipase A2 activity (PLA2) in vitro, and may function as endogenous suppressors of lipolysis. To probe the possible role of lipid peroxidation in the regulation of myocardial lipid catabolism, a neutral-active and Ca2+-dependent PLA2 was extracted from rat heart and was partially purified by sulfopropyl cation exchange chromatography. Myocardial PLA2 activity was inhibited in a dose-dependent manner by oleic, linoleic, linolenic, and arachidonic acids; the IC50 for arachidonic acid was approx 65 microM. Palmitic acid was not inhibitory. When arachidonic acid was incubated at 37 degrees C, exposed to air, there was a time- and pH-dependent peroxidation of the arachidonic acid as monitored by turbidity, thiobarbituric acid reactivity, and thin layer chromatography. Peroxidation was increased as the pH was lowered from 7.5 to 4.5, and was accompanied by a decrease in PLA2 inhibitory potency. Thus, arachidonate incubated for 24 hours at pH's 4.5, 6.0 and 7.5 lost 84%, 32%, and 20% respectively, of its inhibitory potency. Therefore, in vitro acidosis promotes the oxidation of cis-unsaturated fatty acids and relieves their inhibitory or suppressive activity toward PLA2s. Increased lipid peroxidation of unesterified unsaturated fatty acids during acidosis may therefore promote lipolysis observed during myocardial ischemia and reperfusion injury.

Reversible inhibition of DNA and protein synthesis by cumene hydroperoxide and 4-hydroxy-nonenal

To test the possible role of lipid peroxidation in the process of in vitro ageing, human diploid skin fibroblasts were cultured with the lipophilic hydroperoxide cumene hydroperoxide (Chp) or the breakdown product of lipid peroxidation 4-hydroxy-2,3- trans-nonenal (HNE). Both compounds inhibited cellular DNA and protein synthesis in a dose-dependent way. Cells exposed to Chp or to HNE during growth inhibition recovered DNA and protein synthesis within 24 h upon removal of Chp or HNE from the culture medium. Continuously proliferating cells showed only a partial recovery of DNA and protein synthesis. Pre-culturing cells with the lipophilic free radical scavenger vitamin E did not abolish the effect of Chp upon DNA synthesis. Cellular levels of reduced glutathione (GSH) rose slightly during 1 week of culture with HNE, but remained unaltered with Chp. Neither ATP levels nor cellular energy charges were affected during culture with Chp or HNE. So, DNA synthesis is not impaired due to a shortage of nucleotides nor does GSH protect DNA synthesis against the effects of Chp or HNE. These results suggest that oxygen free-radical induced lipid peroxidation is not the cause of the irreversible loss of proliferation occurring during in vitro ageing.

Possible role of lipid peroxidation in the pathogenesis of arrhythmias in myocardial infarction

The levels of thyroid, pituitary and steroid hormones-thyroxine, triiodothyronine and 11-hydroxycorticosteroids in the blood serum, somatotropin in the pituitary, and processes of protein assimilation were studied in rats in the early postnatal period. The highest endogenous production of thyroxine, triiodothyronine and somatotropin was detected in 15-day-old rats. The highest level of protein utilization was detected in 7 to 15-day-old rats, followed by the lowering of the utilization on changing over to definitive nutrition. Endogenous production of the anabolic hormones thyroxine, triiodothyronine and somatotropin was found to correlate with a high level of protein utilization in rats within the first days of life after birth.

A possible role of lipid peroxidation in cellular damages caused by cerebral ischemia and the protective effect of alpha-tocopherol administration.

Incomplete global cerebral ischemia was induced by clamping the bilateral common carotid arteries of spontaneously hypertensive rats (SHR) and blood reperfusion was allowed by declamping the arteries after indicated times. To investigate the possible role of lipid peroxidation which causes irreversible ischemic cell injury during ischemia and subsequent reperfusion, cerebral energy metabolism, brain edema, neurological signs and cerebral and serum lipid peroxides were examined. The effect of alpha-tocopherol administration on these parameters was also studied from the standpoint of its action as a free radical scavenger. During ischemia up to 5 hours, cerebral ATP decreased and lactate increased rapidly, and concomitantly neurological signs, such as eye closure and jumping seizures, and slowly progressing brain edema were observed. The level of lipid peroxides in the brain and serum remained practically unchanged during ischemia, although an increasing tendency was noted. When blood reperfusion was allowed 3 hours after ischemia, tissue ATP level was restored only partially (67.4% of normal), but lactate returned to the normal level. The reperfusion resulted in a rapid rise in the lipid peroxide level both in cerebral tissue and serum and also caused a more severe expression of neurological signs. Intravenous injection of alpha-tocopherol (20 mg/kg body weight) 30 minutes prior to ligation of the carotid arteries significantly suppressed the rise in lipid peroxides both in the brain and serum, improved the severely expressed neurological signs, and promoted resynthesis of ATP. These improvements in the parameters were observed only after the reperfusion was made following ischemia for 3 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of the chronic ethanol-induced fatty liver by antioxidant administration.

SummaryFemale rats were maintained for 21 days on nutritionally adequate liquid diets containing either “low” or “high” fat content and supplemented with ethanol or isocaloric sucrose as 35% of the calories. Liver triglyceride concentrations were significantly elevated in animals maintained on both diets supplemented with ethanol. However, a greater increment in triglyceride concentrations was manifested in the “high” fat ethanol group under conditions of similar caloric intake. The intraperitoneal administration of the lipid antioxidant, N,N′-diphenyl-p-phenylenediamine (DPPD), prior to, and during the dietary period significantly inhibited the ethanol-induced increment in hepatic triglyceride concentration. The inhibition of the chronic ethanol-induced steatosis, in conjuction with our previous studies of antioxidant modification of the acute ethanol-in-duced hepatic lesion, further accents the possible role of lipid peroxidation as a determinant in cell injury and the role of antioxidants as liver prot...