Lipid Peroxidation In Mice Research Articles

Genipin protects against acute liver injury by abrogating ferroptosis via modification of GPX4 and ALOX15-launched lipid peroxidation in mice.

It is essential to further characterize liver injury aimed at developing novel therapeutic approaches. This study investigated the mechanistic basis of genipin against carbon tetrachloride (CCl4)-triggered acute liver injury concerning ferroptosis, a novel discovered modality of regulated cell death. All experiments were performed using hepatotoxic models upon CCl4 exposure in mice and human hepatocytes in vitro. Immunohistochemistry, immunoblotting, molecular docking, RNA-sequencing and ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) were conducted. CCl4 intoxication was manifested with lipid peroxidation-dictated ferroptotic cell death, together with changes in a cascade of ferroptosis-associated events and several regulatory pathways. Both the administration of genipin and ferrostatin-1 (Fer-1) significantly prevented this hepatotoxicity in response to CCl4 intoxication via upregulating GPX4 and xCT (i.e., critical regulators of ferroptosis). RNA-sequencing unraveled that arachidonic acid metabolism was considerably influenced upon genipin treatment. Accordingly, genipin treatment attenuated arachidonate 15-lipoxygenase (ALOX15)-launched lipid peroxidation in terms of UHPLC-MS/MS analysis and inflammation. In vitro, genipin supplementation rescued erastin-induced hepatocellular inviability and lipid ROS accumulation. The siRNA knockdown of GPX4 partially abrogated the protective effects of genipin on erastin-induced cytotoxicity, whereas the cytotoxicity was less severe in the presence of diminished ALOX15 expression in L-O2 cells. In conclusion, our findings uncovered that genipin treatment protects against CCl4-triggered acute liver injury by abrogating hepatocyte ferroptosis, wherein the pharmacological modification of dysregulated GPX4 and ALOX15-launched lipid peroxidation was responsible for underlying medicinal effects as molecular basis.

A static magnetic field improves bone quality and balances the function of bone cells with regulation on iron metabolism and redox status in type 1 diabetes.

Osteoporosis is one of the chronic complications of type 1 diabetes with high risk of fracture. The prevention of diabetic osteoporosis is of particular importance. Static magnetic fields (SMFs) exhibit advantages on improvement of diabetic complications. The biological effects and mechanism of SMFs on bone health of type 1 diabetic mice and functions of bone cells under high glucose have not been clearly clarified. In animal experiment, six-week-old male C57BL/6J mice were induced to type 1 diabetes and exposed to SMF of 0.4-0.7 T for 4 h/day lasting for 6 weeks. Bone mass, biomechanical strength, microarchitecture and metabolism were determined by DXA, three-point bending assay, micro-CT, histochemical and biochemical methods. Exposure to SMF increased BMD and BMC of femur, improved biomechanical strength with higher ultimate stress, stiffness and elastic modulus, and ameliorated the impaired bone microarchitecture in type 1 diabetic mice by decreasing Tb.Pf, Ct.Po and increasing Ct.Th. SMF enhanced bone turnover by increasing the level of markers for bone formation (OCN and Collagen I) as well as bone resorption (CTSK and NFAT2). In cellular experiment, MC3T3-E1 cells or primary osteoblasts and RAW264.7 cells were cultured in 25 mM high glucose-stimulated diabetic marrow microenvironment under differentiation induction and exposed to SMF. SMF promoted osteogenesis with higher ALP level and mineralization deposition in osteoblasts, and it also enhanced osteoclastogenesis with higher TRAP activity and bone resorption in osteoclasts under high glucose condition. Further, SMF increased iron content with higher FTH1 expression and regulated the redox level through activating HO-1/Nrf2 in tibial tissues, and lowered hepatic iron accumulation by BMP6-mediated regulation of hepcidin and lipid peroxidation in mice with type 1 diabetes. Thus, SMF may act as a potential therapy for improving bone health in type 1 diabetes with regulation on iron homeostasis metabolism and redox status.

THE EFFECT OF BROCCOLI SPROUTS ON OXIDATIVE STRESS MARKERS IN MICE FED WITH CAFETERIA DIET

The aim of our study was to determine the ability of broccoli sprouts to influence the intensity of lipid peroxidation in mice fed a high-calorie cafeteria diet. Materials and methods. In this study, C57BL/6J mice were used. For determinatiom of lipid peroxides (LOOH), we used a method based on the ability of lipid peroxides to convert Fe2+to Fe3+. Then Fe3+ forms a complex with xylenol orange that absorbs light at 580 nm at low pH. The reaction mixture contained coumene hydroperoxide (1 mM), FeSO4*7H2O(1 M), xylenol (4 mM), water and supernatant. Differences between groups were analyzed by Duncan’s test for multiple comparision. Results. During the experiment, we monitored the changes in body mass of mice fed with different diets. There were no differences in LOOH levels in cortexes of mice from all experimental groups, but there was a tendency to the lower content of LOOH in the brain of mice fed with cafeteria diet and broccoli. No statistical differences in levels of LOOH were found between groups, but LOOH levels tended to the highest in the groups fed with broccoli sprouts alone and cafeteria diet. A significant difference was observed in the muscles (C) between the broccoli sprout group and the cafeteria diet + broccoli group. We also found a significant difference between the group fed with the cafeteria diet and the cafeteria diet + broccoli, which may indicate protective effects of broccoli on lipid peroxidation on cafeteria diet. Conclusions. Mice fed with cafeteria diet and broccoli spouts had higher body mass than control mice fed with standard group. Hypothalamus of mice fed with standard diet with broccoli spouts or with cafeteria diet showed a tendency to higher LOOH levels, whereas no effects of the diets were found on cortexes LOOH levels. The cafeteria diet + broccoli group had the lowest muscle LOOH content compared to all other groups. Also, LOOH levels tended to be lower in the cortexes in the hypothalamus of mice fed with cafeteria diet + broccoli as compared with the cafeteria diet group. This suggests the potential protective effects of broccoli spouts.

Hepatitis B virus X protein induces ALDH2 ubiquitin-dependent degradation to enhance alcoholic steatohepatitis.

Excessive alcohol intake with hepatitis B virus (HBV) infection accelerates chronic liver disease progression and patients with HBV infection are more susceptible to alcohol-induced liver disease. Hepatitis B virus X protein (HBx) plays a crucial role in disease pathogenesis, while its specific role in alcoholic liver disease (ALD) progression has not yet been elucidated. Here, we studied the role of HBx on the development of ALD. HBx-transgenic (HBx-Tg) mice and their wild-type littermates were exposed to chronic plus binge alcohol feeding. Primary hepatocytes, cell lines, and human samples were used to investigate the interaction between HBx and acetaldehyde dehydrogenase 2 (ALDH2). Lipid profiles in mouse livers and cells were assessed by using liquid chromatography-mass spectrometry. We identified that HBx significantly aggravated alcohol-induced steatohepatitis, oxidative stress, and lipid peroxidation in mice. In addition, HBx induced worse lipid profiles with high lysophospholipids generation in alcoholic steatohepatitis, as shown by using lipidomic analysis. Importantly, serum and liver acetaldehyde were markedly higher in alcohol-fed HBx-Tg mice. Acetaldehyde induced lysophospholipids generation through oxidative stress in hepatocytes. Mechanistically, HBx directly bound to mitochondrial ALDH2 to induce its ubiquitin-proteasome degradation, resulting in acetaldehyde accumulation. More importantly, we also identified that patients with HBV infection reduced ALDH2 protein levels in the liver. Our study demonstrated that HBx-induced ubiquitin-dependent degradation of mitochondrial ALDH2 aggravates alcoholic steatohepatitis.

Alteration in the activities of antioxidant enzymes and lipid peroxidation in mice transplanted with Dalton’s lymphoma ascites tumor by Helicia Nilagirica Bedd

The present study was performed to obtain an insight into the biochemical profile of Dalton rsquo s lymphoma ascites tumour in Swiss albino mice treated with aqueous extract of Helicia nilagirica The mice bearing Dalton rsquo s lymphoma ascites tumor was injected with mg kg body weight of aqueous extract of H nilagirica for nine consecutive days Thereafter the tumour cells were aspirated at and h post drug treatment for the estimation of glutathione glutathione s transferase catalase superoxide dismutase and lipid peroxidation The administration of tumorized mice with H nilagirica aqueous extract caused a significant depletion in the glutathione contents and activities of glutathione s transferase catalase superoxide dismutase in a time dependent manner up to h post assay time when compared to sterile physiological saline treated group In contrast treatment of tumorized mice with H nilagirica aqueous extract resulted in a time dependent rise in the lipid peroxidation when compared to sterile physiological saline treated group Our study demonstrates that the cytotoxic effect of H nilagirica aqueous extract on Dalton rsquo s lymphoma ascites tumour cells may be due to increased lipid peroxidation and reduction in the glutathione contents activities of glutathione s transferase catalase and superoxide dismutase

Metformin with propofol enhances the scavenging ability of free radicals and inhibits lipid peroxidation in mice.

The aim of this study was to investigate the effects of metformin on anesthetic effect and anti-oxidative capacity in mice anesthetized with propofol. A total of 150 C57BL/6 mice were randomly assigned into the compatibility of an equivalent threshold dose of metformin with propofol group, and compatibility of different doses of metformin with 80 mg/kg propofol group, with 10 subgroups and 15 mice in each. Metformin and propofol were intraperitoneally injected in mice. The induction time of anesthesia in each mouse was recorded. 1 min after the disappearance of righting reflex, serum samples, and brain tissues were harvested, respectively. Subsequently, the contents of superoxide dismutase (SOD), malondialdehyde (MDA), and lactate dehydrogenase (LDH) in serum and brain homogenate of each group were measured. Furthermore, the protein expressions of nuclear factor-kappaB (NF-κB) and Nuclear erythroid 2-related factor 2 (Nrf2) were analyzed by Western blot. Metformin supplementation did not influence the induction time of propofol anesthesia in mice, while the dose of propofol was significantly decreased. Besides, no significant correlation was found between an-esthesia induction time and the dose of metformin. Meanwhile, a certain dose of metformin could markedly increase the SOD activity in mouse brain tissues, whereas it could decrease the serum levels of MDA and LDH. In addition, metformin could remarkably inhibit the NF-κB activity and promote the Nrf2 expression. Metformin improves the anesthetic effect of a single dose or continuous intraperitoneal injection of propofol in mice. The compatibility of a certain dose of metformin with propofol can enhance the scavenging ability of free radicals and their metabolites. Furthermore, this inhibits lipid peroxidation in mice via NF-κB inhibition and Nrf2 activation.

Nimesulide effects on the blood pro-oxidant–antioxidant status in lipopolysaccharide-challenged mice

The maintenance of the pro-oxidant–antioxidant equilibrium between ROS production and antioxidant protection systems is an important element of systemic defence and requires efficient control. The aim of the study was to monitor the dynamics of antioxidants and lipid peroxidation in mice challenged intraperitoneally with Escherichia coli (O111:B4) lipopolysaccharide (LPS) and to evaluate the antioxidant potential of the non-steroidal anti-inflammatory drug nimesulide. Albino mice were divided into three groups (n = 36). Group I received a single intraperitoneal (i.p.) injection with 25 μg/0.5 mL LPS. Thirty minutes before LPS, group II received orally (p.o.) 100 mg/kg nimesulide. The preparation was administered for 4 days. Group III received only nimesulide at the indicated dose for 4 days. The blood parameters were analysed at hour 0 (prior to treatment applied to each group), post treatment hours 6 and 24, and days 3, 5 and 9. Assayed parameters included catalase, reduced glutathione, albumin, glucose, ferric reducing ability of plasma (FRAP), malondialdehyde and oxidative stress index. LPS induced continuous hypoglycaemia, decreased catalase activity and reduced glutathione, but FRAP and albumin were preserved. The application of nimesulide alone did not alter oxidative stress index and enhanced FRAP. Its co-administration with LPS normalised reduced glutathione, decreased catalase and increased malondialdehyde concentrations and oxidative stress index. The application of nimesulide as antioxidant requires objective evaluation of associated benefits and risks.

Effect of Buddleja scordioides K. leaves infusion on lipid peroxidation in mice with ultraviolet light-induced oxidative stress

The aim of the study was to evaluate the effect of Buddleja scordioides Kunth leaves infusion on lipid peroxidation in mice with ultraviolet (UV) light-induced oxidative stress. CD-1 mice were allocated into treatment and control groups (n = 8). Mice in the intervention group were treated with B. scordioides leaves infusion (500 µL equivalent to 0.6534 mg of lyophilized leave infusion/kg of body weight) while the controls received distilled water by gavage administration during 9 days. Both groups were UV irradiated (2.59320175 mW/cm2) 4 consecutive days: 3 h per day with rest periods of 4 min every hour. B. scordioides leaves infusion had high concentrations of hydroxybenzoic acids, flavonols, hydroxycinnamic acids, and flavone compounds. Mice previously treated with B. scordioides leaves infusion exhibited a significant reduction on malondialdehyde (MDA) concentrations in the liver (77%) but not in kidney and plasma in comparison with the control group. B. scordioides leaves infusion shows hepatoprotective activity via free radical scavenging in mice with UV light-induced oxidative stress.

Zinc sulfate pretreatment prevents carbon tetrachloride-induced lethal toxicity through metallothionein-mediated suppression of lipid peroxidation in mice

Zinc sulfate pretreatment prevents carbon tetrachloride-induced lethal toxicity through metallothionein-mediated suppression of lipid peroxidation in mice

Antioxidant activity and inhibitory effect of some commonly used medicinal plants against lipid per-oxidation in mice brain.

The present study compares the protective properties of aqueous extracts of six medicinal plants, Phyllanthus emblica, Terminalia chebula (black and yellow), Terminalia arjuna, Balsamodendron Mukul and Alium sativum against lipid per-oxidation in mice brain. The antioxidant activities were analyzed by lipid per-oxidation assay, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical assay, total antioxidant activity and metal chelation. The extracts (fruits and bark) showed inhibition against thiobarbituric acid reactive species (TBARS) induced by pro-oxidant (10 µM FeSO4) in mice brain. Moreover, the free radical scavenging activities of the extracts was evaluated by the scavenging of DPPH radical (IC₅₀, 23.23 ± 1.2 µg/ml (Phyllanthus emblica), 20.24 ± 0.9 µg/ml (Terminalia chebula yellow) and 17.33 ± 1.1 µg/ml (Terminalia chebula black), 19.44 ± 0.45 µg/ml (Terminalia arjuna), 56.59 ± 2.1 µg/ml (Balsamodendron Mukul) and < 200 µg/ml (Alium sativum). The higher antioxidant and inhibitory effect of Terminalia chebula black in this study could be attributed to its significantly higher phenolic content, Fe(II) chelating ability, reducing ability and free radical scavenging activity. Therefore oxidative stress in brain could be potentially prevented by the intake of these plants.

Hypolipidemic, hypoglycemic, and antioxidative effects of a new pigmented rice cultivar “Superjami” in high fat-fed mice

Effects of newly-developed pigmented rice Superjami, in comparison with those of its parental cultivars (Heugjinjubyeo and Suweon 425) and ordinary brown rice, on the lipid and glucose metabolisms and antioxidative defense status in high fatfed mice were investigated. The animals were randomly divided and given experimental diets for eight weeks: normal control, high fat, and high fat supplemented with ordinary brown, Heugjinjubyeo, Suweon 425 or Superjami rice powder. Their body weight, plasma lipid profile, blood glucose level, and lipid peroxidation were measured. The enzymes and hormones involved in the lipid and glucose metabolisms were also analyzed. High fat feeding significantly increased the body weight, total cholesterol, triglyceride, blood glucose, and lipid peroxidation in mice. On the other hand, diet supplementation of the rice samples, particularly Superjami, markedly reduced the body weight gain, improved the lipid and glucose profiles, and suppressed oxidative stress through regulation of hepatic lipogenesis and adipokine production, inhibition of glucose-regulating enzymes, and enhancement of antioxidant enzyme activities. Superjami has greater hypolipidemic, hypoglycemic, and antioxidant status-improving effects than its parental cultivars. This study provides the first evidence of the physiological effect of Superjami, which may be useful in the prevention and management of high fat diet-induced hyperlipidemia, hyperglycemia, and oxidative stress.

Silymarin alleviates bleomycin-induced pulmonary toxicity and lipid peroxidation in mice

Context: The application of bleomycin is limited due to its side effects including lung toxicity. Silymarin is a flavonoid complex isolated from milk thistle [Silybum marianum L. (Asteraceae)] which has been identified as an antioxidant and anti-inflammatory compound.Objective: This study evaluates the effect of silymarin on oxidative and inflammatory parameters in the lungs of mice exposed to bleomycin.Materials and methods: BALB/c mice were divided into four groups of control, bleomycin (1.5 U/kg), bleomycin plus silymarin (50 and 100 mg/kg). After bleomycin administration, mice received 10 d intraperitoneal silymarin treatment. On 10th day, blood and lung samples were collected for measurement of oxidative and inflammatory factors.Results: Silymarin led to a decrease in lung lipid peroxidation (0.19 and 0.17 nmol/mg protein) in bleomycin-injected animals. Glutathione-S-transferase (GST) which was inhibited by bleomycin (32.4 nmol/min/mg protein) induced by higher dose of silymarin (41 nmol/min/mg protein). Silymarin caused an elevation in glutathione (GSH): 2.6 and 3.1 µmol/g lung compare with bleomycin-injected animals 1.8 µmol/g lung. Catalase (CAT) was increased due to high dose of silymarin (65.7 µmol/min/ml protein) compare with bleomycin treated-mice. Myeloperoxidase (MPO) which was induced due to bleomycin (p < 0.05) reduced again by high dose of silymarin (0.51 U/min/mg protein). Bleomycin led to an increase in TNF-α and interleukin-6 (IL-6) (7.9 and 11.8 pg/ml). These parameters were reduced by silymarin (p < 0.05).Conclusions: Silymarin attenuated bleomycin induced-pulmonary toxicity. This protective effect may be due to the ability of silymarin in keeping oxidant–antioxidant balance and regulating of inflammatory mediator release.

Effects of intragastric administration of formaldehyde on superoxide dismutase activities and malondialdehyde contents in liver of mice

To study the effects of intragastric administration of formaldehyde on lipid peroxidation in mice. Thirty ICR mice were randomly divided into 3 groups: one control group and two experimental groups. The mice were given formaldehyde (the dose is 0, 5 and 20 mg/kg body weight respectively) through intragastric administration once a day for 5 days , and then they were killed. The activities of SOD and the contents of MDA in liver were measured. The activities of SOD in the 20 mg/kg body weight group were significantly lower than the control group (P < 0.05), and the contents of MDA in the 20 mg/kg body weight group were significantly higher than the control group (P < 0.05), and the liver organ coefficient in the 20 mg/kg body weight group is higher than the control group (P < 0.05). A certain dose of formaldehyde can destroy the balance of lipid peroxidation in mice, the ability of antioxidation is reduced obviously, and the liver become compensatory hypertrophy.

Evaluation of Acetaminophen Effect on Oxidative Stressed Mice by Peroxide Hydrogen

Acetaminophen (Paracetamol) is among the most commonly used analgesic and antipyretic drugs worldwide, it’s often, but anomalously, classified as non-steroidal anti-inflammatory drugs (NSAIDs) in textbooks of pharmacology . This study aims to evaluate if paracetamol has an antioxidant effect, relative to its analgesic antipyretic and weak anti-inflammatory activities, or it possesses a cytotoxic potential. Oxidative stress was induced by intraperetoneal injection of peroxide hydrogen (H2O2), and then a comparative study is made concerning the activities of the antioxidant enzymes SOD, CAT, and GR as well as lipid peroxidation levels in liver. An increase in SOD, CAT, GR activity and lipid peroxidation in mice treated with H2O2 accompanied by paracetamol; compared to the group treated by vitamin C + H2O2 showed that acetaminophen doesn’t show any antioxidant effect. Moreover this study has suggested that acetaminophen induced cytotoxicity in liver mediated by increased oxidative stress and altered redox metabolism.

High-fat diets rich in ω-3 or ω-6 polyunsaturated fatty acids have distinct effects on lipid profiles and lipid peroxidation in mice selected for either high body weight or leanness

ObjectiveThe aim of the study is to determine the response of muscle lipid peroxidation and the fatty-acid profile of three groups of mice—high body weight (DU6) obesity-prone mice, high treadmill performance (DUhTP) lean mice, and unselected control mice (DUK) fed high-fat diets (HFDs) rich in ω-3 or ω-6 polyunsaturated fatty acids (PUFA). MethodsThe isocaloric HFDs were enriched with either ω-3 PUFA (27% fish oil, ω-3 HFD) or ω-6 PUFA (27% sunflower oil, ω-6 HFD), and the control group was fed standard chow (7.2% fat). Statistical calculations were done with procedure GLM of SAS. ResultsAs expected, the ω-3 and ω-6 PUFA-rich HFDs showed significant effects on fatty-acid concentrations of skeletal muscle in all three lines of mice compared with the standard chow. The investigations of muscle lipid peroxidation revealed that the ω-3 PUFA-rich HFD caused the highest lipid peroxidation values in muscle of lean DUhTP mice and unselected control DUK mice. However, lower lipid peroxidation levels were observed in the obesity-prone DU6 mice. In contrast, the ω-6 PUFA-rich HFD did not influence lipid peroxidation in muscle of any of the different lines of mice. The present study suggests that a higher overall antioxidant capacity in the muscle tissue of obesity-prone DU6 mice may lead to lower levels of reactive oxygen species formation by ω-3 PUFA-rich HFDs in comparison with lean DUhTP mice. ConclusionThese studies raise the possibility that obesity per se may be protective against oxidative damage when high ω-3 PUFA diets are used.

Teduglutide, a glucagon-like peptide 2 analogue: A novel protective agent with anti-apoptotic and anti-oxidant properties in mice with lung injury

Teduglutide is a long-acting synthetic analogue of human glucagon-like peptide-2 (GLP-2). GLP-2 regulates cell proliferation and apoptosis as well as normal physiology in the gastrointestinal tract. In the present study, possible cytoprotective and reparative effects of teduglutide were analyzed on a mouse model with lung injury induced by tumor necrosis factor-alpha (TNF-α) and actinomycin D (Act D). BALB/c mice were divided into six groups: control mice (I), mice injected intraperitoneally with 15μg/kg TNF-α (II), 800μg/kg Act D (III), Act D 2min prior to TNF-α administration with the same doses (IV), mice injected subcutaneously with 200μg/kg teduglutide every 12h for 10 consecutive days (V), and mice given Act D 2min prior to TNF-α administration on day 11 after receiving teduglutide for 10 days (VI). The TNF-α/Act D administration made the lung a sensitive organ to damage. Mice lung subjected to TNF-α/Act D were characterized by the disruption of alveolar wall, induced pulmonary endothelial/epithelial cell apoptosis and expression of active caspase-3. These mice exhibited an increase in lipid peroxidation, glutathione levels, and activities of myeloperoxidase, superoxide dismutase, catalase, glutathione peroxidase and xanthine oxidase, as well as reduced tissue factor and sodium–potassium/ATPase activities. Teduglutide pretreatment regressed the structural damage, cell apoptosis and oxidative stress by reducing lipid peroxidation in mice received TNF-α/Act D. GLP-2 receptors were present on the cell membrane of type II pneumocytes and interstitial cells. Thus, teduglutide can be suggested as a novel protective agent, which possesses anti-apoptotic and anti-oxidant properties, against lung injury.

Effects of Zingiber officinale extract on antioxidation and lipid peroxidation in mice after exposure to 60Co-γ-ray

Zingber officinale extract (ZOE) has been demonstrated to protect mice against radiation-induced sickness and mortality. In this study, we investigated protective ability of ZOE against anti-oxidative damage induced by non-lethal dose of 60 Coγ-ray. The optimum dose was selected by giving mice 0, 100, 200, 400, 800 or 1600 mg/kg body weight (B.W.) of ZOE (oral gavage) p.o. once daily for five days. Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities increased, and malondialdehyde (MDA) contents decreased along with an increase in the ZOE dose of up to 800 mg/kg body weight. ZOE at dose of 800 mg/kg B.W. showed the best effect by enhancing anti-oxidative function and reducing lipid peroxidation. The activities of SOD, CAT and GSH-Px increased significantly, while MDA content decreased significantly in ZOE (800 mg/kg) + irradiation(IR) group when compared with double distilled water (DDW) + IR group (p<0.05). These results indicate that ZOE at 800 mg/kg body weight could provide protection against anti-oxidative damage in irradiated mice. Key words : Zingiber officinale extract, 60Co, γ-ray, mice, free radical, superoxide dismutase (SOD), radiation, antioxidants.

Modifications on antioxidant capacity and lipid peroxidation in mice under fraxetin treatment.

Fraxetin belongs to an extensive group of natural phenolic antioxidants. We have investigated the modifications in endogenous antioxidant capacity; superoxide dismutase (SOD), catalase (CAT), total and selenium-dependent glutathione peroxidases (GPx) and glutathione reductase (GR) and stress index; glutathione disulphide (GSSG)/reduced glutathione (GSH) ratio and thiobarbituric acid-reactive substances (TBARs) in liver and brain supernatants of C57BL/6J male 12-month-old mice under fraxetin treatment for 30 days. Liver SOD and GPx (total and Se-dependent) activities were not significantly affected by fraxetin, whereas they were increased in the brain compared with control animals. GR activity increased significantly only in the liver of treated mice. Fraxetin treatment-related decreases were shown for GSSG/GSH ratio and rate of accumulation of TBARs (not significant in TBARs) in both tissues. We concluded that the net effect of fraxetin treatment on endogenous antioxidant capacity suggests that this compound might provide an important resistance to, or protection against, free-radical-mediated events which contribute to degenerative diseases of ageing.

Anti-hepatotoxic effects of 3,4-methylenedioxyphenol and N-acetylcysteine in acutely acetaminophen-overdosed mice

3,4-Methylenedioxyphenol (sesamol) is effective against acetaminophen-induced liver injury in rats. Whether sesamol's anti-hepatotoxic effect is comparable to that of N-acetylcysteine has never been studied. We investigated the anti-hepatotoxic effects of sesamol and N-acetylcysteine on acetaminophen-induced hepatotoxicity in mice. Equimolar doses (1 mmol/kg) of sesamol and N-acetylcysteine significantly inhibited acetaminophen (300 mg/kg)-increased serum aspartate transaminase and alanine transaminase levels 6 h post-administration. Sesamol and N-acetylcysteine maintained hepatic glutathione levels and inhibited lipid peroxidation. Moreover, the combination of sesamol and N-acetylcysteine antagonistically inhibited sesamol's protection against acetaminophen-induced liver injury. We conclude that the protective effect of sesamol against acetaminophen-induced liver damage is comparable to that of N-acetylcysteine by maintaining glutathione levels and inhibiting lipid peroxidation in mice.

Bifidobacterium longum HY8004 attenuates TNBS-induced colitis by inhibiting lipid peroxidation in mice

To investigate the mechanisms of the preventive activity of lactic acid bacteria in colitis, the inhibitory effect of Bifidobacterium longum HY8004, which potently inhibited lipid peroxidation in vitro, was examined in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitic mice. We measured the ability of lactic acid bacteria (LAB) to inhibit lipid peroxidation in vitro and to inhibit colitis outcomes, colon shortening, and myeloperoxidase activity in TNBS-induced colitis in C3H/HeN and C3H/HeJ mice. We also measured levels of the inflammatory markers interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha and their transcription factor, NF-kappaB, in the colon by enzyme-linked immunosorbent assay and immunoblot analysis. Among the LAB tested, B. logum HY8004 most potently inhibited lipid peroxidation in vitro but did not inhibit TLR-4-linked NF-kappaB activation in HEK cells. Oral administration of HY8004 inhibited TNBS-induced colon shortening and myeloperoxidase activity in the colon of C3H/HeN and C3H/HeJ mice as well as IL-1 beta and TNF-alpha expression. B. longum HY8004 also inhibited TNBS-induced lipid peroxidation, TLR-4 expression, and NF-kappaB activation in the colon of C3H/HeN and C3H/HeJ mice. B. longum HY8004 can improve colitis via the inhibition of lipid peroxidation as well as NF-kappaB activation.