BACKGROUND: To observe the effect of linear alkylbenzenesulfonate (LAS) on oxidative stress and collagen fiber in skin tissue of mice and to explore the correlation between oxidative stress and collagen metabolism.
 METHODS: Forty healthy Kunming mice (male) were randomly divided into 4 groups: a control group, a low-, middle- and high-dose group of LAS (LD, MD and HD groups), treated with LAS at 150, 300 and 600 mg/L respectively (n=10 per group). The skin on the back of mice was smeared with distilled water or different dosage of LAS for 60 days. The measured indexes included general condition of mice, HE and Masson staining of skin, the content of hydroxyproline (Hyp) in skin tissue, the activity of super oxidase dismutase (SOD) and the content of malondialdehyde (MDA) in skin tissue and serum, and the activity of lactate dehydrogenase (LDH) in serum.
 RESULTS: Compared with the control group, the changes of diet, daily activities and mental state of mice with different dose of LAS were not obvious during the experiment, but the body weight of mice in the experimental groups reduced obviously after 4 weeks of experiment (P<0.01), and their skin tissue was thinner, some of epidermis of skin contained areas with cellular necrosis and abscission. Superficial layer of dermis was infiltrated by inflammatory cells. The collagen fibers were looser and dimmer. At the same time, the content of MDA and the activity of LDH increased remarkably (P<0.01), while the activity of SOD and the content of Hyp decreased obviously (P<0.01).
 CONCLUSIONS LAS can induce oxidative stress in the skin tissue of mice, which can destroy the integrity of skin structure and collagen fiber and reduce the content of collagen fiber. The oxidative damage might be the primary cause for disorders of collagen fiber.
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Alkanesulfonic Acids ; pharmacology ; Animals ; Collagen ; metabolism ; Male ; Malondialdehyde ; metabolism ; Mice ; Oxidative Stress ; Skin ; drug effects ; metabolism

The aim of this study was to investigate the harmful effects of acute hypoxia on mouse cerebral cortex and hippocampus and the underlying mechanism. Mouse model of acute hypoxia was constructed by using a sealed glass jar. Laser speckle contrast imaging was used to detect the changes of cerebral blood flow after different time duration of hypoxia. Total superoxide dismutase (T-SOD) and malondialdehyde (MDA) assay kits were used to detect oxidative stress in cerebral cortex and hippocampus. Immunofluorescent staining was used to detect neuroinflammatory response of microglia in the cerebral cortex and hippocampus. One-step TUNEL method was used to detect neuronal apoptosis. The results showed that, compared with non-hypoxia (0 min hypoxia) group, 30 min hypoxia group exhibited decreased cerebral blood flow, higher percentage of CD68⁺/Iba1⁺ microglia, and increased neural apoptosis in the cerebral cortex and hippocampus. Compared with 30 min group, 60 min hypoxia group showed significantly decreased cerebral blood flow, increased MDA content in the cortex, as well as greater percentage of CD68⁺/Iba1⁺ microglia and neuronal apoptosis in the cerebral cortex and hippocampus. These results suggest that acute hypoxia damages brain tissue in a time-dependent manner and the oxidative stress and neuroinflammation are important mechanisms.
Animals ; Cerebral Cortex/metabolism* ; Hippocampus/metabolism* ; Hypoxia ; Malondialdehyde ; Mice ; Oxidative Stress ; Superoxide Dismutase/pharmacology*

OBJECTIVETo evaluate therapeutic and antioxidant effects of Uygur Herb Foeniculum Vulgare Mill (FVM) in hepatic fibrosis rats.

METHODHepatic fibrosis model was built in rats by subcutaneous injection with 40% CCl4 olive oil mixture. At the same time the rats were given high lipoid-low protein animal feeds for 5 weeks. 94 male SD rats were randomly divided into six groups :blank control group (A-group), 8 rats were feed in normal; prevention model control group (B-group), 10 rats were given saline solution by intragastric administration during make of hepatic fibrosis model; FVM prevention group (C-group), 10 rats were given FVM by intragastric administration during make of hepatic fibrosis model; model control group (D-group), FVM treatment group (E-group); Fuzhenghuayu treatment group (F-group). 22 rats in each D, E, F-group were respectively given saline solution, FVM and Fuzhenghuayu by intragastric administration after hepatic fibrosis model were built. At the 5-th weekend, A, B, C- group rats were sacrificed. At the 6-th, 7-th, 8-th, 9-th weekend, 4-6 rats in D, E, F-group were sacrificed. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), laminin (LN) and 8 - hydroxy-2-deoxyguanosine (8-OHdG) were detected, liver tissue homogenate superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA) were detected. Histopathologic changes were observed after H.E and Masson staining. The expression of alpha-smooth muscle actin(a-SMA) were detected by immunohistochemical staining. The data were analyzed by SPSS17.0 software.

RESULTSThe serum levels of ALT, AST, HA, and LN in the FVM prevention group were significantly reduced compared to the prevention model control group.(P less than 0.05). Rats in FVM treatment group appeared a marked lower serum levels of ALT, AST, HA compared to the model control group (P less than 0.05), and a distinguished lower Inflammation grade and fibrosis stage (P less than 0.05) when the liver section were assayed as well; Rats in FVM treatment group and FVM prevention group had a conspicuous lower content of MDA, 8-OHdG, fibre and a-SMA expression (P less than 0.05), a significantly higher level of SOD, GSH-Px compared to those of in the model control groups.

CONCLUSIONSFoeniculum Vulgare Mill declines liver inflammation response ,and prevent the hepatic fibrosis progression,, this may be due to its effects of antioxidative results.

Animals ; Antioxidants ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Foeniculum ; Liver Cirrhosis, Experimental ; metabolism ; pathology ; Male ; Malondialdehyde ; metabolism ; Plant Oils ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism

The investigation on the stem bark of Morus wittiorum was carried out to find its chemical constituents possessing anti-oxidative activity. The isolation and purification were performed by various chromatographies such as silica gel, Sephadex LH-20, RP-C18 column chromatography and so on. Based on the spectral analysis such as NMR, MS, etc., seven 2-arylbenzofuran derivatives were identified as wittifuran D (1), wittifuran E (2), moracin C (3), moracin M (4), moracin P (5), 2-(3,5-dihydroxyphenyl)-5,6-dihydroxybenzofuran (6) and mulberroside C (7). Compounds 1-7 were isolated from this plant for the first time. Among them, 1 and 2 were new compounds. Compounds 3-7 were used to assay antioxidant activity, the inhibitory ratios of compounds 3, 4, 6, at a concentration of 1 x 10(-5) mol x L(-1), to malondialdehyde (MDA) produced during microsomal lipid peroxidation induced by ferrous-cysteine were 73%, 69% and 89% respectively.
Antioxidants ; isolation & purification ; pharmacology ; Benzofurans ; chemistry ; isolation & purification ; pharmacology ; Lipid Peroxidation ; Malondialdehyde ; chemistry ; Molecular Structure ; Morus ; chemistry ; Plant Bark ; chemistry ; Plants, Medicinal ; chemistry ; Stilbenes ; chemistry ; isolation & purification ; pharmacology

OBJECTIVETo investigate the protective effect of marine collagen peptides (MCPs) on the skin of aged mice induced by D-galactose.

METHODSSubchronic toxicity study was conducted while D-galactose induced subacute aging model was established. D-galactose dose of 0.125 g/kg body weight was intraperitoneally injected daily for 90 days. Marine collagen peptide 0.225, 0.450, 1.350 g/kg body weight were administered by oral gavage. Superoxide dismutase (SOD), catalase (CAT) activity and malondialdehyde (MDA) content in blood serum were measured, along with cutaneous histopathology examination.

RESULTSEpidermal thickness was significantly higher in MCPs treated group. Number and activity of fibroblast in MCPs treated dermis was increased prominently. The activity of SOD in 0.225, 0.450, 1.350 g/kgbw MCPs treated groups were 455.52 +/- 11.39, 460.15 +/- 18.09, 468.59 +/- 27.25 U/ml respectively, each of which was significantly higher than that in model control group; the activity of serum CAT in 0.225, 1.350 g/kgbw MCPs treated groups (21.33 +/- 4.82, 21.69 +/- 1.68 U/ml) were obviously increased compared with that in model control group (17.14 +/- 2.81 U/ml); MDA level in 0.450, 1.350 g/kgbw MCPs treated groups were 5.67 +/- 0.93, 5.76 +/- 1.02 nmol/ml respectively, each of which was significantly lower than that in model control group (7.63 +/- 1.37 nmol/ml).

CONCLUSIONSThe results showed that MCPs might play a protective role on skin aging by improving the activity of antioxidant.

Animals ; Antioxidants ; pharmacology ; Collagen ; pharmacology ; Male ; Malondialdehyde ; blood ; Marine Biology ; Mice ; Peptides ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Skin Aging ; drug effects ; Superoxide Dismutase ; blood

In this study, solid dispersion technology was used to develop volatile oil from Acorus tatarinowii self-nanoemulsion dropping pills(VOA-SNEDDS-DP) and its protective effect on acute myocardial ischemia injury was evaluated. Taking exterior quality, weight variation and the resolving time as comprehendsive evaluation indexes, the preparation process and formulation of the dropping pills were optimized by orthogonal design, and the dissolution rate in vitro of the optimized VOA-SNEDDS-DP was investigated. The rat model of acute myocardial ischemia was induced by intraperitoneal injection of isoproterenol hydrochloride and the serum levels of superoxide dismutase(SOD), malondialdehyde(MDA), creatine kinase(CK) and pathological changes of myocardial tissue were determined to evaluate therapeutic effect of the dropping pills on acute myocardial ischemia. The results showed that the optimal formulation and preparation process of VOA-SNEDDS-DP were as follows: PEG6000-PEG8000 was 1∶1, proportion of VOA-SNEDDS and matrix was l∶2.5, the temperature of drug fluids was 75 ℃, drop rate was 35 drops/min, drop distance was 5 cm, the condensing agent temperature was 2-10 ℃. The content of β-asarone in the dropping pills was 42.46 mg·g~(-1). The accumulated dissolution rate of the dropping pills reached 93.85% in 10 min. The results of pharmacodynamic experiments showed that VOA-SNEDDS-DP could significantly increase the SOD content(P<0.05), reduce the levels of MDA and CK(P<0.05) in serum, and effectively improve the pathological morphology of myocardial tissue. These results revealed that the preparation of VOA-SNEDDS-DP by solid dispersion technology was stable and feasible, and VOA-SNEDDS-DP had protective effect on acute myocardial ischemia injury.
Acorus ; chemistry ; Animals ; Creatine Kinase ; blood ; Drugs, Chinese Herbal ; pharmacology ; Malondialdehyde ; blood ; Myocardial Ischemia ; drug therapy ; Oils, Volatile ; pharmacology ; Plant Oils ; pharmacology ; Rats ; Superoxide Dismutase ; blood

OBJECTIVETo evaluate the protective effect of polydatin on a PC12 cell model of oxygen and glucose deprivation (OGD).

METHODSA pheochromocytoma cell injury model was induced by OGD to simulate the cerebral ischemic changes. The protective effects of polydatin were investigated in this model.

RESULTSPolydatin treatment significantly enhanced the cell viability and reduced the levels of lactate dehydrogenase, nitric oxide and the malondialdehyde of the pheochromocytoma cells as compared with the OGD group. Polydatin also increased the activity of superoxide dismutase in the cells.

CONCLUSIONPolydatin offers protective effect against OGD-induced injury in pheochromocytoma cells.

Animals ; Brain Ischemia ; metabolism ; prevention & control ; Cell Survival ; Glucose ; metabolism ; pharmacology ; Glucosides ; pharmacology ; L-Lactate Dehydrogenase ; analysis ; Malondialdehyde ; analysis ; Nitric Oxide ; analysis ; Oxygen ; metabolism ; pharmacology ; PC12 Cells ; Protective Agents ; pharmacology ; Rats ; Stilbenes ; pharmacology ; Superoxide Dismutase ; metabolism

AIMOxidized low-density lipoprotein (LDL) is involved in the development of atherosclerosis. Oxidative modulation of serum LDL is related to oxygen free radicals. Antioxidants have beneficial effects on oxidative modulation of LDL and development of atherosclerosis. Salvia miltriorhiza (Danshen) preparations have been widely used in the treatment of cardio-cerebral vascular diseases in China. Salvianolic acid A (Sal-A), one of the components of Salvia miltriorhiza, was shown to have strong antioxidative activity. The aim of this investigation was to evaluate the effect of Sal-A on human LDL oxidative modulation mediated by copper ions.

METHODSOxidation of human LDL was performed in pH 7.4 phosphate-buffered saline with 10 mumol.L-1 CuSO4 at 37 degrees C water for 20 h. The content of malondialdehyde (MDA), lipofuscin and vitamin E in LDL as well as the rate of electrophoretic mobility (REM) of LDL were measured. The generation of free radicals during LDL oxidation was detected by low level-chemiluminescence (LL-CL). The chelation of Cu2+ by Sal-A was detected by UV-spectrum scanning.

RESULTSSal-A (10(-6) to 10(-4) mol.L-1) was shown to markedly reduce the production of MDA and lipofuscin as well as the consumption of vitamin E during LDL oxidation. Sal-A (10(-4) mol.L-1) was also shown to inhibit the increase of REM of LDL caused by oxidative modification. In addition, the spectrum of LL-CL showed that Sal-A (10(-6) to 10(-5) mol.L-1) decreased the generation of free radicals during LDL oxidation in a dose dependent manner. The differential UV-spectrum of Sal-A in the presence of Cu2+ indicated that Sal-A could chelate copper ions.

CONCLUSIONSal-A has inhibitory effect on Cu2+ mediated human LDL oxidation through chelating Cu2+ and scavenging free radicals.

Antioxidants ; pharmacology ; Caffeic Acids ; pharmacology ; Copper ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Free Radical Scavengers ; pharmacology ; Humans ; Lactates ; pharmacology ; Lipofuscin ; metabolism ; Lipoproteins, LDL ; metabolism ; Malondialdehyde ; metabolism ; Oxidation-Reduction ; drug effects ; Vitamin E ; metabolism

OBJECTIVETo investigate the effects of Pyrroloquinoline quinine (PQQ) on hydrogen peroxide-induced apoptosis of Schwann cells (SCs) and its mechanism.

METHODSSCs were isolated and cultured in vitro, and identified by S-100 immunofluorescence staining. The cultured SCs were divided into control group, hydrogen peroxide-treated group, hydrogen peroxide and PQQ treated groups. The intracellular superoxide dismutase (SOD) and malondialdehyde (MDA) content was detected; the apoptotic rate of SCs induced by hydrogen peroxide was determined by flow cytometry assay. The Hoechst33342 staining was used to detect the nuclear fragmentation and apoptotic nuclear condensation of SCs; the Rhodamine123 staining was used to detect the changes of mitochondrial membrane potential in SCs, the Western blot analysis was used to detect the expression of Bcl-2 in hydrogen peroxide induced SCs.

RESULTSThe SOD activity was significantly decreased and MDA level was increased in H2O2 induced SCs (P < 0.05), after addition of PQQ, the SOD content increased and MDA content decreased (P < 0.05). Flow cytometry results showed that the early apoptotic rate was 58.8% in H2O2 induced SCs, which has significant difference compared with the control group (P < 0.05), after addition of 10, 50, 100 nmol/L PQQ, the apoptotic rates were reduced to 33.7%, 18.7%, 3.9% respectively, showing significantly different with injured group (P < 0.05). Hoechst 33342 staining showed that H2O2 induced SCs had typical morphological characteristics, such as uptake of nuclear chromatin, nuclear shrinkage, nuclear fragmentation phenomenon. The proportion of apoptotic cells after PQQ treatment reduced. Rhodamine staining results showed that the H2O2 induced mitochondrial membrane potential reduction in SCs, which was reversed by addition of PQQ. Western blot analysis showed that the expression of Bcl-2 was decreased in H2O2 induced SCs, while it increased significantly after addition of PQQ (P < 0.05).

CONCLUSIONPQQ has a protective effect on oxidative stress-induced apoptosis of SCs.

Apoptosis ; drug effects ; Benzimidazoles ; Cell Nucleus ; drug effects ; DNA Fragmentation ; Fluorescent Dyes ; Humans ; Hydrogen Peroxide ; pharmacology ; Malondialdehyde ; metabolism ; Oxidants ; pharmacology ; Oxidative Stress ; Pyrroles ; pharmacology ; Quinine ; pharmacology ; Quinolines ; pharmacology ; Schwann Cells ; cytology ; drug effects ; Superoxide Dismutase ; metabolism

OBJECTIVES: To investigate the effect and mechanism of lipid nanoparticle (LNP) delivery of small interfering RNA (siRNA) targeting Cyp2e1 gene on subacute alcoholic liver injury in mice. METHODS: siRNA targeting Cyp2e1 gene was encapsulated in LNP (si-Cyp2e1 LNP) by microfluidic technique and the resulting LNPs were characterized. The optimal dose of si-Cyp2e1 LNP administration was screened. Forty female C57BL/6N mice were randomly divided into blank control group, model control group, si-Cyp2e1 LNP group, LNP control group and metadoxine group. The subacute alcoholic liver injury mouse model was induced by ethanol feeding for 10 d plus ethanol gavage for the last 3 d. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, and the superoxide dismutase (SOD) activity as well as malondialdehyde, reactive oxygen species, glutathione, triacylglycerol, total cholesterol contents in liver tissue were measured in each group, and liver index was calculated. The expression of genes related to oxidative stress, lipid synthesis and inflammation in each group of mice were measured by realtime RT-PCR. RESULTS: Compared with the model control group, the levels of liver index, serum ALT, AST activities, malondialdehyde, reactive oxygen species, triacylglycerol, total cholesterol contents in liver tissue decreased, but the SOD activity as well as glutathione increased in the si-Cyp2e1 LNP group (all P<0.01). Hematoxylin-eosin staining result showed disorganized hepatocytes with sparse cytoplasm and a large number of fat vacuoles and necrosis in the model control group, while the si-Cyp2e1 LNP group had uniformly sized and arranged hepatocytes with normal liver tissue morphology and structure. Oil red O staining result showed si-Cyp2e1 LNP group had lower fat content of the liver compared to the model control group (P<0.01), and no fat droplets accumulated. Anti-F4/80 monoclonal antibody fluorescence immunohistochemistry showed that the si-Cyp2e1 LNP group had lower cumulative optical density values compared to the model control group (P<0.01) and no significant inflammatory reaction. Compared with the model control group, the expression of catalytic genes P47phox, P67phox and Gp91phox were reduced (all P<0.01), while the expression of the antioxidant enzyme genes Sod1, Gsh-rd and Gsh-px were increased (all P<0.01). The mRNA expression of the lipid metabolism genes Pgc-1α and Cpt1 were increased (all P<0.01) and the lipid synthesis-related genes Srebp1c, Acc and Fasn were decreased (all P<0.01); the expression of liver inflammation-related genes Tgf-β, Tnf-α and Il-6 were decreased (all P<0.01). CONCLUSIONS The si-Cyp2e1 LNP may attenuate subacute alcoholic liver injury in mice mainly by reducing reactive oxygen levels, increasing antioxidant activity, blocking oxidative stress pathways and reducing ethanol-induced steatosis and inflammation.
Animals ; Female ; Mice ; Antioxidants/metabolism* ; Cholesterol/metabolism* ; Ethanol/pharmacology* ; Glutathione/pharmacology* ; Inflammation ; Lipids/pharmacology* ; Liver ; Malondialdehyde/pharmacology* ; Mice, Inbred C57BL ; Oxidative Stress ; Reactive Oxygen Species/metabolism* ; RNA, Small Interfering/pharmacology* ; Superoxide Dismutase ; Triglycerides/metabolism* ; Cytochrome P-450 CYP2E1/metabolism*