Lipid Oxidative Markers Research Articles

Early post-mortem sarcoplasmic proteome of porcine muscle related to lipid oxidation in aged and cooked meat

In order to identify specific markers of lipid oxidation generated in meat during refrigerated storage and cooking an analysis was conducted to investigate the relationships between the early post-mortem sarcoplasmic proteome, which contains the majority of enzymes involved in the oxidative process, and the level of lipid oxidation. This study was performed in Longissimus lumborum pig muscle. Proteome was analysed by 2-D electrophoresis in combination with liquid chromatography–tandem mass spectrometry (LC–MS/MS) and lipid oxidation was estimated by the TBA reactive substances (TBA-RS) measurement. Many markers of lipid oxidation were identified, but no single marker covered the oxidative process in its entirety. The role of five protein groups (albumin, redoxins, annexins, lipid transporters and enzymes of aerobic respiration), from which a link with lipid oxidation can be established, is discussed. This study, which completes a precedent work focused on protein oxidation, clearly demonstrates that a combination of several markers is needed to assess the sensitivity of meat to oxidation during both ageing and cooking.

Association of age-related changes in circulating intermediary lipid metabolites, inflammatory and oxidative stress markers, and arterial stiffness in middle-aged men

The relationships between age-related changes in circulating endogenous metabolites, inflammatory and oxidative stress markers, and arterial stiffness in 57 middle-aged (34–55 years), nonobese men were studied over the course of 3 years. Arterial stiffness was measured using brachial-ankle pulse wave velocities (ba-PWV). Plasma metabolomic profiling was performed using ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry. After 3 years, decreased HDL cholesterol and increased malondialdehyde (MDA) and ox-LDL levels were observed. Among 15 identified lipids, lysoPCs (C16:0, C18:0, C18:2, C20:4, and C20:5) and linoleyl carnitine were the major plasma metabolites that contributed to the age-related differences. LysoPC16:0 (variable importance in the projection value, 6.2029) was found as the most important plasma metabolite for evaluating these changes. Changes in lysoPC16:0 levels positively correlated with the changes in 8-epi-PGF2α (r = 0.608), MDA (r = 0.413), high-sensitivity C-reactive protein (r = 0.509), IL-6 (r = 0.497), and ba-PWV (r = 0.283) levels. ba-PWV levels positively correlated with the changes in waist-to-hip ratios (WHR), inflammatory and oxidative stress markers. In a subgroup analysis of subjects with decreased ba-PWVs vs. increased ba-PWVs, changes in WHR and levels of lysoPC16:0, ba-PWV, IL-6, 8-epi-PGF2α, MDA, and P-selectin were significantly different. Our results suggest that age-related increases in lysoPC16:0 may contribute to lipid peroxidation, thereby activating proinflammatory phenotypes and arterial stiffness.

Lipid biomarkers of oxidative stress in a genetic mouse model of Smith‐Lemli‐Opitz syndrome

7-Dehydrocholesterol (7-DHC) accumulates in tissues and fluids of patients with Smith-Lemli-Opitz syndrome (SLOS), which is caused by mutations in the gene encoding 3β-hydroxysterol-Δ(7)-reductase (DHCR7). We recently reported that 7-DHC is the most reactive lipid molecule toward free radical oxidation (lipid peroxidation) and 14 oxysterols have been identified as products of oxidation of 7-DHC in solution. As the high oxidizability of 7-DHC may lead to systemic oxidative stress in SLOS patients, we report here lipid biomarkers of oxidative stress in a Dhcr7-KO mouse model of SLOS, including oxysterols, isoprostanes (IsoPs), and neuroprostanes (NeuroPs) that are formed from the oxidation of 7-DHC, arachidonic acid and docosahexaenoic acid, respectively. In addition to a previously described oxysterol, 3β,5α-dihydroxycholest-7-en-6-one (DHCEO), we provide evidence for the chemical structures of three new oxysterols in the brain and/or liver tissue of Dhcr7-KO mice, two of which were quantified. We find that levels of IsoPs and NeuroPs are also elevated in brain and/or liver tissues of Dhcr7-KO mice relative to matching WT mice. While IsoPs and NeuroPs have been established as a reliable measurement of lipid peroxidation and oxidative stress in vivo, we show that in this genetic SLOS mouse model, 7-DHC-derived oxysterols are present at much higher levels than IsoPs and NeuroPs and thus are better markers of lipid oxidation and related oxidative stress.

Oxidación de proteínas y lípidos en cerebro de cobayos durante la exposición a grandes alturas (4540 m)

El objetivo del presente estudio fue evaluar el efecto del tiempo de exposición a grandes alturas sobre la oxidación de proteínas y lípidos en el tejido cerebral de cobayos. Se utilizaron cincuenta cobayos nativos del nivel del mar: 10 permanecieron en su hábitat (Lima, 150 m) sirviendo de control, y cuarenta fueron trasladados a Morococha, 4540 m, y sacrificados los días 1, 3, 7 y 14 después de su arribo. Se determinaron: la actividad de fosfolipasa A2 (FLA2), los niveles de hidroperóxidos lipídicos (LOOH) y malondialdehído (TBARS), como marcadores de la oxidación de lípidos; nivel de grupos carbonílicos (GC), como marcadores de la oxidación de proteínas; y la actividad de las enzimas antioxidantes superóxido dismutasa (SOD), catalasa (CAT) y glutatión peroxidasa (GPx). La actividad de FLA2 aumentó hasta el tercer día. Se encontró niveles de LOOH, TBARS y GC incrementados al primer día; LOOH mostró tendencia a disminuir durante el experimento; TBARS mantuvo sus niveles altos y GC disminuyó por debajo del nivel de control al tercer día. Las actividades de las enzimas antioxidantes, GPx y CAT, incrementaron desde el primer día; la actividad de SOD aumentó hasta el tercer día y disminuyó posteriormente. Se concluye que la exposición a grandes alturas influye directamente en el proceso de oxidación de lípidos y proteínas. La disminución de los niveles de GC podría deberse a la activación del sistema proteolítico, que degradaría las proteínas dañadas por las EROs (especies reactivas del oxígeno). La exposición a la altura influye además en la actividad de las enzimas antioxidantes, especialmente GPx, por su importante rol en la detoxificación de LOOH.

Static Headspace Gas Chromatographic Method for Aldehyde Determination in Crackers

The aim of this work was to develop and validate static headspace gas chromatography with flame ionization detection method for determination of five aldehydes selected as markers for lipid oxidation, present in freshly baked and stored crackers with high fat content. Chromatographic conditions defined in this method allow the separation of propanal, pentanal, hexanal, heptanal and octanal within 15 min. Relative standard deviations (RSD) of the retention times for repeatability and intermediate precision for all compounds were less than 1.75 and 0.22 %, respectively. For the obtained peak areas, RSD for repeatability and intermediate precision were less than 3.86 and 4.32 %, respectively. Recovery was within the range of 60–99 %. Each analyte showed an excellent linear behaviour over the set concentration range, with correlation coefficient (R2) values above 0.99. Limits of quantification for propanal, pentanal, hexanal, heptanal and octanal were 0.10, 0.05, 0.08, 0.02 and 0.02 μg, respectively. The proposed method accomplishes the requirements for the method selectivity, precision, sensitivity, accuracy and linearity needed for determination of aldehydes in bakery products. Quantification of aldehydes was achieved for both freshly baked and stored crackers over a long period of time.

Influence of Punica granatum L. on region specific responses in rat brain during Alloxan-Induced diabetes

ObjectiveThe present study was carried out to investigate the effects of Punica granatum peel methanolic extract (PGPE) on cerebral cortex (CC) and Hippocampus (HC) brain antioxidant defense system and markers of lipid and protein oxidation in alloxan induced diabetic rats. MethodsOral administration of PGPE (75 and 150 mg of kg body weight) for 45 days resulted in significant reduction in blood glucose levels. ResultsSupplementation of diabetic rats with PGPE showed increased activities of SOD and GPx with concomitant decrease in MDA and PC content. Region-specific changes were more evident in the HC when compared to CC. ConclusionsThe present study indicated that PGPE can ameliorate brain oxidative stress in alloxan induced diabetic rats by up regulating antioxidant defense mechanism by attenuating lipid and protein oxidation. PGPE thus may be used as a potential therapeutic agent in preventing diabetic complications in the brain.

The effect of different doses and types of intravenous iron on oxidative stress and inflammation in hemodialysis patients

Although intravenous iron (IVI) is thought to have potential inflammatory and atherogenic effects, there are not enough studies comparing these effects in chronic hemodialysis (HD) patients. In this study, different doses and types of IVI were examined for effects on inflammation and oxidative stress. Chronic HD patients (n=101) were grouped into those not receiving IVI (group 1, n=29), those getting intermittent iron sucrose (group 2, n=25), those receiving intermittent iron dextran (group 3, n=24) and those getting a once monthly total dose of iron dextran (group 4, n=23). Malondialdehyde (MDA), advanced oxidation protein product (AOPP), C-reactive protein (CRP) and TNF-α levels were measured on days 0, 2, 7 and 28. Groups were similar regarding age, sex, hemoglobin, iron indices and total amount of IVI given monthly. Although MDA levels at days 7 and 28, AOPP levels at days 0 and 28, CRP levels at day 28 and TNF-α level at day 7 were higher than at other days, there were no significant differences between the IVI groups on statistical analysis. The different types and doses (intermittent or once monthly total dose) of IVI treatments are well tolerated without negative effects on the markers of lipid and protein oxidation and inflammatory indices in chronic HD patients.

Oxidative stress status in metastatic breast cancer patients receiving palliative chemotherapy and its impact on survival rates

Antineoplastic agents are known to induce the production of free radicals leading to cell damage. These adverse effects may fuel the acquisition of new mutations and the development of treatment resistances. We selected 30 metastatic breast cancer patients receiving palliative chemotherapy, and paired blood samples, before and after chemotherapy, were extracted. We analysed DNA, lipid and protein oxidative damage markers and determined the extent of antioxidant and repair defences activation at the systemic level. We found that the DNA repair activity of the KU86 enzyme was significantly lower after chemotherapy and the antioxidant capacity of the plasma was significantly higher after treatment. Cox regression analysis revealed a significant effect of KU86 activity on the survival rates of those patients who received anthracyclines as part of their treatment. The high clinical heterogeneity of metastatic breast cancer patients warrants further studies to clarify the role of DNA repair and systemic antioxidant capacities during chemotherapy.

Assessment of the oxidative stability of conventional and high-oleic sunflower oil by means of solid-phase microextraction-gas chromatography

Headspace-solid-phase microextraction-gas chromatography (HS-SPME-GC) was used to identify in total 74 volatile lipid oxidation compounds altogether in thermally stressed conventional and high-oleic sunflower (HOSF) oil samples (in accelerated storage conditions for 14 days at 80°C). Out of the volatile compounds identified, six volatile compounds were selected as marker compounds for the assessment of lipid oxidation of sunflower (SF) and HOSF oils due to their low odour threshold values and fatty-rancid odour impression. Additionally, other oxidation parameters such as fatty acid composition, peroxide value (PV), anisidine value and tocopherol and tocotrienol composition were determined. Multivariate statistical methods (principal component analysis and agglomerative hierarchical cluster analysis) were applied to identify sensitive oxidation marker compounds. Preliminary results revealed that hexanal, E-2-heptenal, E-2-decenal and E,E-2,4-nonadienal were the most suitable in differentiating HOSF and SF oil varieties from each other and SF samples with differing oxidative properties. Differentiation of SF samples according to their volatile compound composition was done in accordance with the results from the well-known oil quality parameters (e.g. PV or fatty acid composition). In conclusion, the combination of volatile compound analysis with HS-SPME-GC and multivariate statistical methods provides a sensitive tool in differentiating conventional SF and HOSF oils by means of volatile lipid oxidation marker compounds.

Effect of the consumption of a fruit and vegetable soup with high in vitro carotenoid bioaccessibility on serum carotenoid concentrations and markers of oxidative stress in young men

To evaluate the effect of the daily intake of a fruit & vegetable soup with high in vitro bioaccessibility of carotenoids on β-carotene and lycopene serum concentrations. Fourteen healthy young men (24±1years) received 300mL/day of a carrot, tomato, and broccoli soup, containing 3.9mg β-carotene and 4mg lycopene, for 4weeks followed by a 4-week washout period. The serum carotenoid response and oxidative markers were analyzed after 3 and 4weeks of soup consumption and after a 4-week washout. The in vitro bioaccessibility of β-carotene and lycopene was 55 and 43%, respectively, in the soup. Serum β-carotene concentrations were significantly higher than baseline (0.33±0.05μmol/L) after 3weeks (0.69±0.06μmol/L) and 4weeks (0.78±0.10μmol/L) of soup consumption (P<0.001). Serum lycopene was also significantly higher compared with baseline levels (0.26±0.08-0.56±0.04μmol/L and 0.60±0.04μmol/L, after 3 and 4weeks, respectively) (P<0.001). Although the highest concentration of both carotenoids was found after 4weeks, the levels were not statistically different from the levels at 3weeks. A 4-week washout significantly decreased serum carotenoid concentrations, although only β-carotene returned to baseline. Glutathione peroxidase (GPx) increased significantly after soup supplementation compared with baseline, while superoxide dismutase was significantly lower only after 3weeks. Glutathione reductase, lipid, protein, and DNA oxidative markers remained unchanged. The soup contributed to increasing the concentration of each carotenoid by more than 100% after 3 and 4weeks of consumption, the maximum increase being observed after 4weeks. Oxidative markers did not show any variation except for GPx. Serum lycopene half-life was longer than that of β-carotene, which may be important for studies evaluating both carotenoids.

Heat-induced volatiles and odour-active compounds in a model cheese

The aim of this work was to identify and characterize the volatile compounds formed during the cooking of a model cheese. Particular attention was paid to the generation of the odour-active volatile fraction, which can contribute to the sensory characteristics of cheeses. To this end we used various analytical methods including two-dimensional gas chromatography coupled with time-of-flight mass spectrometry and chromatography–olfactometry. The changes observed in the volatile fraction enabled us to follow several markers of lipid oxidation, caramelization and Maillard reaction mechanisms during cooking. Maltol and furaneol, though present in only trace amounts, gave rise to “overcooked” odour defects in the cheese matrices.

Relationship of oxidized low density lipoprotein with lipid profile and oxidative stress markers in healthy young adults: a translational study

BackgroundDespite oxidized low density lipoprotein (ox-LDL) plays important roles in the pro-inflammatory and atherosclerotic processes, the relationships with metabolic and oxidative stress biomarkers have been only scarcely investigated in young adult people. Thus, the aim of this study was to assess plasma ox-LDL concentrations and the potential association with oxidative stress markers as well as with anthropometric and metabolic features in healthy young adults.MethodsThis study enrolled 160 healthy subjects (92 women/68 men; 23 ± 4 y; 22.0 ± 2.9 kg/m2). Anthropometry, body composition, blood pressure, lifestyle features, biochemical data, and oxidative stress markers were assessed with validated tools. Selenium, copper, and zinc nail concentrations were measured by atomic absorption spectrophotometry.ResultsTotal cholesterol (TC), LDL-c and uric acid concentrations, TC-to-HDL-c ratio, and glutathione peroxidase (GPx) activity were positive predictors of ox-LDL concentrations, while nail selenium level (NSL) was a negative predictor, independently of gender, age, smoking status, physical activity. Those individuals included in the highest tertile of GPx activity (≥611 nmol/[mL/min]) and of NSL (≥430 ng/g of nail) had higher and lower ox-LDL concentrations, respectively, independently of the same covariates plus truncal fat or body mass index, and total cholesterol or LDL-c concentrations.ConclusionsOx-LDL concentrations were significantly associated with lipid biomarkers, GPx activity, uric acid concentration, and NSL, independently of different assayed covariates, in young healthy adults. These findings jointly suggest the early and complex relationship between lipid profile and redox status balance.

과체중 이상 성인에서 혈중 콜레스테롤 수준에 따른 영양소 섭취량, 혈중 산화 및 염증 관련 지표에 관한 연구

This study was designed to investigate the relationships among blood lipid levels, nutrient intakes, oxidation and inflammation markers of overweight adults(23<TEX>$\leq$</TEX>BMI<25) and obese(BMI<TEX>$\geq$</TEX>25) in Korea. The subjects were classified as control, borderline hyperlipidemia. and hyperlipidemia groups based on The Korean Guidelines of Hyperlipidemia Treatment for the Prevention of Atherosclerosis. The study was conducted through questionnaires, anthropometric checkups, 2-days of 24 hr recalls, and blood biomarker analyses. Systolic blood pressure(SBP) was significantly increased in the hyperlipidemia group(p=0.0464). Intakes of nutrients were not significantly different among the three groups. Blood oxidized-LDL levels were significantly increased in the hyperlipidemia group(p<0.0001). Blood triglyceride(TG) levels were positively associated with BMI(p=0.0498), SBP(p=0.0158), and diastolic blood pressure(DBP; p=0.0076). Blood total cholesterol levels were positively associated with SBP(p=0.0005), and blood HDL-cholesterol levels were negatively associated with body fat (p=0.0408). Blood LDL-cholesterol levels were negatively associated with height(p=0.0207), and blood VLDL-cholesterol levels were positively associated with SBP(p=0.0011) and DBP(p=0.0490). Intakes of protein(p=0.0257) and dietary fiber (p=0.0094) were positively associated with blood HDL-cholesterol levels. Frap levels were positively associated with TG levels(p=0.0001) and VLDL-cholesterol levels(p=0.0077). Oxidized-LDL levels were positively associated with LDL-cholesterol levels(p=0.0135). These results suggest that oxidation and inflammation markers may be related to hypercholesterolemia progress, and dietary fiber intake may play a role in preventing hyperlipidemia in overweight and obese adults.

Effect of dioxin exposure on several indices of blood redox status in lactating buffalo cows

Dioxins are lipophilic compounds with a small molecular weight and are highly persistent, bioaccumulative and toxic. Dioxin detoxification is associated with an increased production of reactive oxygen species (ROS). In physiological conditions the body is protected against ROS and their toxic products by a wide range of antioxidant systems. We hypothesize that the imbalance between ROS production, associated with dioxin exposure, and the antioxidant defence capacity, may lead to oxidative stress, with consequent increased consumption of antioxidants and accumulation of toxic compounds in blood and tissues. The objective of this study was to evaluate the effect of exposure to dioxins on the plasma redox status of lactating buffalo cows. To this aim, the major liposoluble (retinol and α-tocopherol) and water-soluble (ascorbate) antioxidants, the superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity, the total antioxidant capacity (TAC), as well as specific protein oxidation markers (protein bound carbonyls and nitro-tyrosine) and lipid oxidation markers (hydroperoxides), were chosen as indices of blood redox status. The concentration of antioxidants, protein-bound carbonyls (PC), nitro-tyrosine (N-Tyr), and hydroperoxides (LPO), the SOD and GPx activity, and the TAC were measured in plasma samples obtained from buffalo cows exposed to environmental levels of dioxins higher (n=21, group A) or lower (n=29; group B) than those permitted. Plasma titres of antioxidants, as measured by HPLC, and the total antioxidant capacity, as measured by trolox equivalents capacity, were higher in group B than in A. Similarly, SOD and GPx activities were higher in group B than in A. Conversely, plasma levels of PC, N-Tyr and LPO, as measured by ELISA, were higher in group A than in B. Our results suggest that exposure to dioxins impairs the plasma antioxidant defence system of lactating buffalo cows, and that metabolic processes associated with dioxin detoxification might induce or enhance oxidation of protein and lipids. This adverse effect on blood redox status might have negative implications for animal health and reproduction, and might compromise animal welfare.

Effects of Coenzyme Q10 on Arterial Stiffness, Metabolic Parameters, and Fatigue in Obese Subjects: A Double-Blind Randomized Controlled Study

This study investigated the effects of coenzyme Q(10) supplementation on metabolic parameters, inflammatory markers, arterial stiffness, and fatigue in obese subjects. We performed a randomized, double-blind, placebo-controlled, single-center study on 51 obese subjects with a body mass index (BMI) of ≥25 kg/m(2). Subjects were randomized into either a coenzyme Q(10) (200 mg/day) group (n = 26, BMI = 27.9 ± 2.3 kg/m(2), age = 42.7 ± 11.3 years) or a placebo group (n = 25, BMI = 26.8 ± 2.8 kg/m(2), age = 41.3 ± 11.2 years) for a 12-week study. We collected anthropometric measurements, blood for laboratory testing, brachial-ankle pulse wave velocity (baPWV) as an indicator of arterial stiffness, and responses to a fatigue severity scale (FSS) questionnaire at the initial (0 week) and final (12 weeks) visits. A total of 36 subjects successfully completed the study protocol. Serum coenzyme Q(10) levels increased significantly from 0.65 ± 0.27 μg/mL to 1.20 ± 0.38 μg/mL in the coenzyme Q(10) group (P < .001). Oral administration of coenzyme Q(10) did not significantly affect lipid profiles, oxidative and inflammatory markers [including lipoprotein (a), oxidized low-density lipoprotein level, C-reactive protein, and white blood cell count], or baPWV. The mean FSS score decreased significantly from 40.1 to 33.1 in the coenzyme Q(10) group (P = .017), but no significant change was seen in the placebo group (P = .464). However, the extents of the change in mean FSS score between the placebo and coenzyme Q(10) groups were not significantly different (P = .287). In conclusion, we found no evidence that coenzyme Q(10) affects fatigue index, arterial stiffness, metabolic parameters, or inflammatory markers.

A headspace solid-phase microextraction gas-chromatographic mass-spectrometric method (HS-SPME–GC/MS) to quantify hexanal in butter during storage as marker of lipid oxidation

A method using headspace solid-phase microextraction (HS-SPME) combined with gas chromatography–mass spectrometry (GC/MS) was developed and validated for the extraction and quantification of hexanal content in butter (at ngg−1 level) during storage at 4°C. The variability of hexanal content among seasons of production and the influence of high extraction temperature on ex-novo formation of hexanal were also evaluated. The HS-SPME conditions were optimised and analytical parameters of the method (linearity, accuracy, and precision) demonstrate its usefulness. The reproducibility and accuracy of the quantitative analysis was assured by the use of D12-hexanal as internal standard. For the applications, the headspace was extracted using CAR/PDMS fiber for 180min at 4°C. Hexanal contents in samples during all storage period (shelf-life) and from butters produced in different seasons were analysed. Butter samples at the end of shelf-life and samples produced in August showed highest values of hexanal, confirming that the temperature both in storage and distribution phases represents a critical factor to maintain the quality of butter.

Quantification of hexanal as an index of lipid oxidation in human milk and association with antioxidant components

Hexanal, a secondary product of lipid oxidation, was identified as the major volatile aldehyde generated from lipid peroxidation in human milk. Hexanal was quantified in human milk using solid phase microextraction-gas chromatography/flame ionization detection that required correction for recovery based on the fat content of human milk. Alpha-tocopherol was the only tocopherol isomer in human milk found to be significantly correlated with hexanal (R = −0.374, p<0.05) and the total antioxidant capacity of human milk (ORACFl (R = 0.408, p<0.01)). Ascorbic acid content was negatively correlated (R = −0.403, p<0.05) with hexanal, but not to ORACFl in human milk. The effect of Holder pasteurization on oxidative status of human milk was determined using multiple parameters that included, hexanal level and malondialdehyde as markers of lipid oxidation, vitamins C and E content and antioxidant capacity (e.g. ORACFl). Pasteurization did not affect the oxidative status of milk as measured by hexanal level, ORACFl and malondialdehyde content. We conclude that hexanal is a sensitive and useful chemical indicator for assessing peroxidation reactions in human milk and that alpha tocopherol and ascorbic acid are two key antioxidant components in milk that contribute to protection against oxidation of milk lipids.

Hypolipidemic and antioxidant activity of aqueous extract of Monascus purpureus fermented Indian rice in high cholesterol diet fed rats

To evaluate hypolipidemic and anti-oxidant activities of Monascus purpureus fermented Indian variety of rice. Materials and methods: Indian rice variety IR-532-E-576 was fermented with Monascus purpureus MTCC 1090 (Monascaceae) and extracted with water by boiling. Experimentally induced hyperlipidemia was produced by feeding rats with 2% cholesterol enriched diet for 15 days. Afterwards hypercholesterolemic rats were orally administered with Monascus fermented Indian rice extract at the dose of 1.2 and 2.4 mg/kg bw along with high cholesterol diet for 30 successive days in order to evaluate their expected hypolipidemic activity. Plasma lipid parameters such as total cholesterol, triglycerides, LDL (low density lipoprotein), VLDL (very low density lipoprotein), HDL (high density lipoprotein), atherogenic index, and oxidative stress markers such as lipid peroxidation, reduced glutathione, and superoxide dismutase, and catalase activities were measured in the plasma and liver respectively. Results: The administration of Monascus fermented Indian rice extract retained lipid profiles and oxidative stress markers to about normal level and also produced a significant decrease in atherogenic index to about 98.07% and 99.53% for 1.2 and 2.4 mg/kg bw Monascus fermented Indian rice extract. It also showed better in vitro and in vivo antioxidant activity with IC_{50} of 250 ± 0.2 µg/ mL and 245 ± 0.12 µg/mL by DPPH (diphenylpicrylhydrazyl) radical scavenging activity and metal chelating activity respectively. Conclusion: The consumption of Monascus fermented Indian rice may act as a potent anti-hypercholesterolemic nutrient and powerful antioxidant.

Expressions of Lipid Oxidation Markers, N.EPSILON.-Hexanoyl Lysine and Acrolein in Cisplatin-Induced Nephrotoxicity in Rats

The purpose of this study was to evaluate whether N(ε)-hexanoyl lysine (N(ε)-HEL) and acrolein reflect the severity of cisplatin-induced nephrotoxicity. Immunoexpression of N(ε)-HEL and acrolein in kidneys and their urinary concentration were examined up to day 4 post-cisplatin injection in rats. Cisplatin-induced tubular injury was observed histopathologically on days 2-4 after injection and became more severe time-dependently. On days 2-4, N(ε)-HEL and acrolein were immunostained in the cytoplasm of damaged tubular cells. Their immunostaining intensity and urinary levels increased as tubular injury became more severe. These results suggest that expressions of N(ε)-HEL and acrolein were associated with the pathogenesis of cisplatin-induced nephrotoxicity.

P53-Mediated Oxidative Stress and Tubular Injury in Rats with Glycerol-Induced Acute Kidney Injury

Background/Aims: p53 is a transcriptional factor that responds to severe cell damage promoting the transcription of proapoptotic and prooxidant genes. In this study, we evaluated the role of p53 activation in glycerol-induced acute kidney injury (Gly-AKI). Methods: Rats were treated with p53 inhibitor (pifithrin-α) in the moment we injected glycerol. Renal function, renal histology (HE), TUNEL labeling, cleaved caspase-3 staining, renal p53, Bax, PUMA, Bcl-2, p21 and survivin expressions, renal lipid and DNA oxidative markers, and the expression of antioxidant enzymes (Mn-SOD, HO-1, and NAD(P)H:quinone-oxidoreductase-1) were evaluated. Results: Gly-AKI rats showed an increased renal expression of phosphorylated-p53. The p53 inhibitor attenuated renal impairment and significantly reduced tubular injury. The expression of the oxidative markers was significantly reduced in treated rats. Proapoptotic and prooxidant proteins Bax and PUMA were overexpressed in Gly-AKI rats and reduced in treated rats. On the contrary, antiapoptotic Bcl-2, p21, and survivin showed a tendency to increase in treated rats. The antioxidant enzymes’ expression remained elevated or increased in treated rats. Conclusion: On the whole, p53 inhibition was protective in the short term. The oxidative stress subsided and the transcription tipped toward prosurvival genes; consequently tubular injury was attenuated in treated rats.