锌胁迫对桉树巯基物质含量及抗氧化酶活性的影响

通过桉树的水培实验,测定了不同浓度Zn胁迫下桉树的生物量,根和叶中Zn、巯基物质(非蛋白巯基,谷胱甘肽和植物络合素)和丙二醛(MDA)的含量,以及根中抗氧化酶的活性。从巯基物质含量和抗氧化酶活性的角度,探讨了桉树抵御Zn胁迫造成氧化性伤害的机制。实验结果表明,Zn浓度较低(20 mg/L和40 mg/L)时,根中MDA含量非显著性增加,抗氧化酶超氧化物歧化酶(SOD)、过氧化物酶(POD)和过氧化氢酶(CAT)的活性上升,叶中巯基物质含量非显著性增加。Zn浓度较高(120 mg/L和140 mg/L)时,根中MDA含量显著性增加,SOD、POD和CAT的活性下降,叶中巯基物质含量显著性增加。因此,低浓度Zn胁迫时,桉树中巯基物质和抗氧化酶系统对氧化性伤害有较好的缓解作用;高浓度Zn胁迫时,大量过氧化物积累,桉树中巯基物质和抗氧化酶系统对氧化损伤的缓解作用降低。     

Chaga mushroom extract inhibits oxidative DNA damage in lymphocytes of patients with inflammatory bowel disease

Inflammatory Bowel Disease (IBD) is partly caused by oxidative stress from free radicals and reduced antioxidant levels. Using hydrogen peroxide to induce oxidative stress in vitro in peripheral lymphocytes we investigated the induction of DNA damage supplemented with ethanolic extract of Chaga mushroom as a protective antioxidant. Lymphocytes were obtained from 20 IBD patients and 20 healthy volunteers. For treatment, a constant H_{2}O_{2 } dose (50 microg/ml) was used with variable doses of Chaga extract (10-500 microg/ml). DNA damage was evaluated in 50 cells per individual and dose using the Comet assay (making 1000 observations per experimental point ensuring appropriate statistical power). Chaga supplementation resulted in a 54.9% (p < 0.001) reduction of H_{2}O_{2 } induced DNA damage within the patient group and 34.9% (p < 0.001) within the control group. Lymphocytes from Crohn's disease (CD) patients had a greater basic DNA damage than Ulcerative Colitis (UC) patients (p < 0.001). Conclusively, Chaga extract reduces oxidative stress in lymphocytes from IBD patients and also healthy individuals when challenged in vitro. Thus, Chaga extract could be a possible and valuable supplement to inhibit oxidative stress in general.     

Sensitivity to microcystins: a comparative study in human cell lines with and without multidrug resistance phenotype

Multidrug resistance (MDR) is an obstacle in cancer treatment. An understanding of how tumoral cells react to oxidants can help us elucidate the cellular mechanism involved in resistance. Microcystins are cyanobacteria hepatotoxins known to generate oxidative stress. The aim of this study was to compare the sensitivity to microcystins of human tumoral cell lines with (Lucena) and without (K562) MDR phenotype. Endpoints analyzed were effective microcystins concentration to 50% of exposed cells (EC50), antioxidant enzyme activity, lipid peroxidation, DNA damage, reactive oxygen species (ROS) concentration, and tubulin content. Lucena were more resistant and showed lower DNA damage than K562 cells (P<0.05). Although microcystins did not alter catalase activity, a higher mean value was observed in Lucena than in K562 cells. Lucena cells also showed lower ROS concentration and higher tubulin content. The higher metabolism associated with the MDR phenotype should increase ROS concentration and make for an improved antioxidant defense against the toxic effects of microcystins.     

Genetic damage in cultured human keratinocytes stressed by long-term exposure to areca nut extracts

Chewing betel quid (BQ) is a popular habit worldwide. A causal association between BQ chewing and oral cancer has been well documented. Emerging evidence indicates that sustained exposure to stress induces epigenetic reprogramming of some mammalian cells and increases the mutation rate to accelerate adaptation to stressful environments. In this study, we first confirmed that 24-h treatment with areca nut extracts (ANE; a major component of BQ) at doses over 40 microg/ml induced mutations at the hypoxanthine phosphoribisyltransferase (HPRT) locus in human keratinocytes (HaCaT cells). We then investigated whether the stress of long-term exposure to sublethal doses of ANE (0, 5 and 20 microg/ml for 35 passages) could enhance genetic damage to HaCaT cells. Compared to cells exposed to 0 or 5 microg/ml ANE, cells exposed to 20 microg/ml ANE were slightly but significantly more resistant to a 72-h treatment with ANE and its major ingredients, arecoline and arecaidine, but did not develop cross-resistance to other BQ ingredients or alcohol. The cells that received 20 microg/ml ANE for 35 passages also had a significantly increased mutation frequency at the HPRT locus and an increased frequency in the appearance of micronuclei compared to lower doses. Moreover, increased intracellular levels of reactive oxygen species and 8-hydroxyguanosine in cells exposed to 20 microg/ml ANE suggested that long-term ANE exposure results in the accumulation of oxidative damage. However, cells subjected to long-term treatment of 20 microg/ml ANE contained higher levels of glutathione than unexposed cells. Therefore, after long-term exposure to sublethal doses of ANE, intracellular antioxidative activity may also be enhanced in response to increased oxidative stress. These results suggest that stress caused by long-term ANE exposure enhances oxidative stress and genetic damage in human keratinocytes.     

Free radical scavenging profile and myeloperoxidase inhibition of extracts from antidiabetic plants: Bauhinia forficata and Cissus sicyoides

There is abundant evidence that reactive oxygen species are implicated in several physiological and pathological processes. To protect biological targets from oxidative damage, antioxidants must react with radicals and other reactive species faster than biological substrates do. The aim of the present study was to determine the in vitro antioxidant activity of aqueous extracts from leaves of Bauhinia forficata Link (Fabaceae-Caesalpinioideae) and Cissus sicyoides L. (Vitaceae) (two medicinal plants used popularly in the control of diabetes mellitus), using several different assay systems, namely, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) decolorization, superoxide anion radical (O2(.-)) scavenging and myeloperoxidase (MPO) activity. In the ABTS assay for total antioxidant activity, B. forficata showed IC50 = 8.00+/-0.07 microg/mL, while C. sicyoides showed IC50 = 13.0+/-0.2 microg/mL. However, the extract of C. sicyoides had a stronger effect on O2(.-) (IC50 = 60.0+/-2.3 microg/mL) than the extract of B. forficata (IC50 = 90.0+/-4.4 microg/mL). B. forficata also had a stronger inhibitory effect on MPO activity, as measured by guaiacol oxidation, than C. sicyoides. These results indicate that aqueous extracts of leaves of B. forficata and C. sicyoides are a potential source of natural antioxidants and may be helpful in the prevention of diabetic complications associated with oxidative stress.     

Long-Term Moderate Dose Exogenous Erythropoietin Treatment Protects from Intermittent Hypoxia-Induced Spatial Learning Deficits and Hippocampal Oxidative Stress in Young Rats

Exposure to intermittent hypoxia (IH) is associated with cognitive impairments and oxidative stress in brain regions involved in learning and memory. In earlier studies, erythropoietin (EPO) showed a neuroprotective effect in large doses. The aim of the present study was to explore the effect of smaller doses of EPO, such as those used in the treatment of anemia, on IH-induced cognitive deficits and hippocampal oxidative stress in young rats. The effect of concurrent EPO treatment (500 and 1,000 IU/kg/day ip) on spatial learning and memory deficits induced by long-term exposure to IH for 6 weeks was tested using the Morris water maze (MWM) test and the elevated plus maze (EPM) test. Moreover, the effect on hippocampal glutamate and oxidative stress were assessed. Exposure to IH induced a significant impairment of spatial learning and cognition of animals in both MWM and EPM performance parameters. Moreover, hippocampal glutamate and thiobarbituric acid reactive substances (TBARS) increased while antioxidant defenses (GSH and GSH-Px) decreased. EPO in the tested doses significantly reduced the IH-induced spatial learning deficits in both MWM and EPM tests and dose-dependently antagonized the effects of IH on hippocampal glutamate, TBARS, GSH levels, and GSH-Px activity. Treatment with EPO in moderate doses that used for anemia, concurrently with IH exposure can antagonize IH-induced spatial learning deficits and protect hippocampal neurons from IH-induced lipid peroxidation and oxidative stress-induced damage in young rats, possibly through multiple mechanisms involving a potential antioxidative effect.     

Cytoprotective and antioxidant role of diallyl tetrasulfide on cadmium induced renal injury: an in vivo and in vitro study

Cadmium (Cd) is an environmental and industrial pollutant that affects various organs in humans and animals. A body of evidence has accumulated implicating the free radical generation with subsequent oxidative stress in the biochemical and molecular mechanisms of Cd toxicity. Since kidney is the critical target of Cd toxicity, we carried out this study to investigate the effects of diallyl tetrasulfide (DTS), an organosulfur compound derived from garlic on Cd induced toxicity in the kidney of rats and also in the kidney cell line (vero cells). In experimental rats, subcutaneous administration of Cd (3 mg/kg bw/day) for 3 weeks induced renal damage, which was evident from significantly increased levels of serum urea and creatinine with significant decrease in creatinine clearance. A markedly increased levels of lipid peroxidation markers (thiobarbituric acid reactive substances and lipid hydroperoxides) and protein carbonyl contents with significant decrease in nonenzymic antioxidants (total sulphydryl groups, reduced glutathione, vitamin C and vitamin E) and enzymic antioxidants (superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase) as well as glutathione metabolizing enzymes (glutathione reductase, and glucose-6-phosphate dehydrogenase) were also observed in Cd intoxicated rats. Coadministration of DTS (40 mg/kg bw/day) and Cd resulted in the reversal of the kidney function accompanied by a significant decrease in lipid peroxidation and increase in the antioxidant defense system. In vitro studies with vero cells showed that incubation of DTS (5-50 microg/ml) with Cd (10 microM) significantly reduced the cell death induced by Cd. DTS at 40 microg/ml effectively blocked the cell death and lipid peroxidation induced by Cd (10 microM) indicating its cytoprotective property. Further, the flow cytometric assessment on the level of intracellular reactive oxygen species using a fluorescent probe 2', 7'-dichlorofluorescein diacetate (DCF-DA) confirmed the Cd induced intracellular oxidative stress in vero cells, which was significantly suppressed by DTS (40 microg/ml). The histopathological studies in the kidney of rats also showed that DTS (40 mg/kg bw/day) markedly reduced the toxicity of Cd and preserved the architecture of renal tissue. The present study suggests that the cytoprotective potential of DTS in Cd toxicity might be due to its antioxidant and metal chelating properties, which could be useful for achieving optimum effects in Cd induced renal damage.     

Chronic Melatonin Administration Reduced Oxidative Damage and Cellular Senescence in the Hippocampus of a Mouse Model of Down Syndrome

Previous studies have demonstrated that melatonin administration improves spatial learning and memory and hippocampal long-term potentiation in the adult Ts65Dn (TS) mouse, a model of Down syndrome (DS). This functional benefit of melatonin was accompanied by protection from cholinergic neurodegeneration and the attenuation of several hippocampal neuromorphological alterations in TS mice. Because oxidative stress contributes to the progression of cognitive deficits and neurodegeneration in DS, this study evaluates the antioxidant effects of melatonin in the brains of TS mice. Melatonin was administered to TS and control mice from 6 to 12 months of age and its effects on the oxidative state and levels of cellular senescence were evaluated. Melatonin treatment induced antioxidant and antiaging effects in the hippocampus of adult TS mice. Although melatonin administration did not regulate the activities of the main antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione S-transferase) in the cortex or hippocampus, melatonin decreased protein and lipid oxidative damage by reducing the thiobarbituric acid reactive substances (TBARS) and protein carbonyls (PC) levels in the TS hippocampus due to its ability to act as a free radical scavenger. Consistent with this reduction in oxidative stress, melatonin also decreased hippocampal senescence in TS animals by normalizing the density of senescence-associated β-galactosidase positive cells in the hippocampus. These results showed that this treatment attenuated the oxidative damage and cellular senescence in the brain of TS mice and support the use of melatonin as a potential therapeutic agent for age-related cognitive deficits and neurodegeneration in adults with DS.     

Microcystin-LR induced DNA damage in human peripheral blood lymphocytes

Human exposure to microcystins, which are produced by freshwater cyanobacterial species, is of growing concern due to increasing appearance of cyanobacterial blooms as a consequence of global warming and increasing water eutrophication. Although microcystins are considered to be liver-specific, there is evidence that they may also affect other tissues. These substances have been shown to induce DNA damage in vitro and in vivo, but the mechanisms of their genotoxic activity remain unclear. In human peripheral blood lymphocytes (HPBLs) exposure to non-cytotoxic concentrations (0, 0.1, 1 and 10μg/ml) of microcystin-LR (MCLR) induced a dose- and time-dependent increase in DNA damage, as measured with the comet assay. Digestion of DNA from MCLR-treated HPBLs with purified formamidopyrimidine-DNA glycosylase (Fpg) displayed a greater number of DNA strand-breaks than non-digested DNA, confirming the evidence that MCLR induces oxidative DNA damage. With the cytokinesis-block micronucleus assay no statistically significant induction of micronuclei, nucleoplasmic bridges and nuclear buds was observed after a 24-h exposure to MCLR. At the molecular level, no changes in the expression of selected genes involved in the cellular response to DNA damage and oxidative stress were observed after a 4-h exposure to MCLR (1μg/ml). After 24h, DNA damage-responsive genes (p53, mdm2, gadd45a, cdkn1a), a gene involved in apoptosis (bax) and oxidative stress-responsive genes (cat, gpx1, sod1, gsr, gclc) were up-regulated. These results provide strong support that MCLR is an indirectly genotoxic agent, acting via induction of oxidative stress, and that lymphocytes are also the target of microcystin-induced toxicity.     

Green tea polyphenols inhibit cognitive impairment induced by chronic cerebral hypoperfusion via modulating oxidative stress

Responses to oxidative stress contribute to damage caused by chronic cerebral hypoperfusion, which is characteristic of certain neurodegenerative diseases. We used a rat model of chronic cerebral hypoperfusion to determine whether green tea polyphenols, which are potent antioxidants and free radical scavengers, can reduce vascular cognitive impairment and to investigate their underlying mechanisms of action. Different doses of green tea polyphenols were administered orally to model rats from 4 to 8 weeks after experimentally induced cerebral hypoperfusion, and spatial learning and memory were assessed using the Morris water maze. Following behavioral testing, oxygen free radical levels and antioxidative capability in the cortex and hippocampus were measured biochemically. The levels of lipid peroxidation and oxidative DNA damage were assessed by immunohistochemical staining for 4-hydroxynonenal and 8-hydroxy-2′-deoxyguanosine, respectively. Rats that received green tea polyphenols 400 mg/kg per day had better spatial learning and memory than saline-treated rats. Green tea polyphenols 400 mg/kg per day were found to scavenge oxygen free radicals, enhance antioxidant potential, decrease lipid peroxide production and reduce oxidative DNA damage. However, green tea polyphenols 100 mg/kg per day had no significant effects, particularly in the cortex. This study suggests that green tea polyphenols 400 mg/kg per day improve spatial cognitive abilities following chronic cerebral hypoperfusion and that these effects may be related to the antioxidant effects of these compounds.     

Effects of mercury on antioxidant mechanisms in the marine phanerogam Posidonia oceanica

Biochemical markers of oxidative stress such as catalase activity, glutathione S-transferase (GST) activity and levels of lipid peroxidation evaluated in terms of thiobarbituric acid reactive substances (TBARS) were measured in the sheaths of the marine phanerogam Posidonia oceanica (L.) Delile experimentally exposed to 0.01, 0.1 and 1 microgHg l(-1) for 48 h. Up to a threshold concentration of 0.1 microg Hg l(-1), an increase in catalase and GST activities and TBARS levels was observed, indicating that the antioxidant mechanisms were overtaxed and could not prevent membrane lipid peroxidation. Paradoxically, at 1 microg Hg l(-1), the damage seemed to decrease, as the lipid peroxidation levels of exposed sheaths were lower than those of controls and as catalase and GST activities were not different from those of controls. A possible rapid induction of phytochelatins detoxifying mercury could occur at this high level of mercury.     

The effect of Smallanthus sonchifolius leaf extracts on rat hepatic metabolism

Smallanthus sonchifolius (yacon), originating from South America, has become popular in Japan and in New Zealand for its tubers which contain beta-1,2-oligofructans as the main saccharides. The plant is also successfully cultivated in Central Europe in the Czech Republic in particular. Its aerial part is used in Japan and in Brazil as a component in medicinal teas; while aqueous leaf extracts have been studied for their hypoglycemic activity in normal and diabetic rats. We have already demonstrated the high content of phenolic compounds in yacon leaf extracts and their in vitro antioxidant activity. In this paper, we present the effects of two organic fractions and two aqueous extracts from the leaves of S. sonchifolius on rat hepatocyte viability, on oxidative damage induced by tert-butyl hydroperoxide (t-BH) and allyl alcohol (AA), and on glucose metabolism and their insulin-like effect on the expression of cytochrome P450 (CYP) mRNA. All the extracts tested exhibited strong protective effect against oxidative damage to rat hepatocyte primary cultures in concentrations ranging from 1 to 1000 microg/ml, reduced hepatic glucose production via gluconeogenesis and glycogenolysis at 1000 microg/ml. Moreover, the effects of the organic fractions (200 and 250 microg/ml) and to a lesser extent, the tea infusion (500 microg/ml) on rat CYP2B and CYP2E mRNA expression, were comparable to those observed with insulin. The combination of radical scavenging, cytoprotective and anti-hyperglycemic activity predetermine S. sonchifolius leaves for use in prevention and treatment of chronic diseases involving oxidative stress, particularly diabetes.     

Oxidative stress response of <Emphasis Type="Italic">Synechocystis</Emphasis> sp. (PCC 6803) due to exposure to microcystin-LR and cell-free cyanobacterial crude extract containing microcystin-LR

Cyanobacteria are able to produce a variety of secondary metabolites such as the microcystins. The ecological role of microcystins for the cyanobacteria themselves and in the aquatic ecosystem is not well understood. The aim of this study is to evaluate if microcystins might be used as a communication tool for interspecies cyanobacterial communication via the promotion of oxidative stress. Reactive oxygen species (ROS) are known to be used as plant signals. The main questions relate to the promotion of oxidative stress in Synechocystis sp. via exposure to the cyanobacterial toxins and the physiological effects. This study shows a few markers for oxidative stress, such as the antioxidative enzymes superoxide dismutase, peroxidases and catalases, and cell damage due to extensive generation of ROS leading to lipid peroxidation. End products of lipid peroxidation (malonaldehyde and 4-hydroxynonenal) are conjugated by glutathione S-transferase.     

Phytotoxicity of green synthesized silver nanoparticles on Camelina sativa L

Due to the increased production and release of silver nanoparticles (AgNPs) in the environment, the concerns about the possibility of toxicity and oxidative damage to plant ecosystems should be considered. In the present study, the effects of different concentrations of AgNPs (0, 0.5, 1, 2, 3 and 4 g/L) synthesized using the extract of camelina (Camelina sativa) leaves on the growth and the biochemical traits of camelina seedlings were investigated. The results showed that AgNPs significantly increased Ag accumulation in the roots and shoots which decreased the growth and photosynthetic pigments of camelina seedlings. The highest decrease in the height and total dry weight was observed by 53.1 and 61.8% under 4 g/L AgNPs, respectively over control plants. AgNPs application over 2 g/L enhanced the accumulation of proline, malondialdehyde, hydrogen peroxide and methylglyoxal, and up-regulated the activity of antioxidant enzymes (superoxide dismutase, catalase, ascorbate peroxidase and glutathione reductase) and glyoxalase (glyoxalase I and II) system which indicates oxidative stress induction in camelina seedlings. Moreover, AgNPs reduced ASA and GSH contents and increased DHA and GSSG contents, hence disrupting the redox balance. These results showed that AgNPs at 4 g/L had the most toxic effects on the camelina growth. Therefore, increasing oxidative stress markers and the activity of antioxidant enzymes and enzymes involved in glyoxalase system indicated the oxidative stress induced by AgNPs treatments over 2 g/L as well as the induction of antioxidant defense systems to combat AgNPs-induced oxidative stress.     

Oral exposure to Microcystis increases activity-augmented antioxidant enzymes in the liver of loach (Misgurnus mizolepis) and has no effect on lipid peroxidation

Recently, eutrophication has induced severe cyanobacterial blooms in the Naktong River, the second largest river of Korea. In the present study, lipid peroxidation and the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase, were evaluated in the liver of loach (Misgurnus mizolepis) that were orally exposed to a low dose of Microcystis through dietary supplementation with bloom scum. Loach received 75 mg of dry cells/kg body weight mass (equal to 10 microg microcystin-RR/kg body mass), for 28 days under controlled conditions. Antioxidant enzymatic activity and lipid peroxidation were measured after termination of exposure. The activities of antioxidant enzyme were significantly increased in the livers of toxin-exposed loach after 28 days of exposure, as compared to control fish. However, lipid peroxidation remained stable in both groups. These results suggest that antioxidant enzymes were able to eliminate oxidative stress induced by low concentrations of microcystins and to prevent increased lipid peroxidation in the liver of loach.     

20-Hydroxyecdysone Protects against Oxidative Stress-Induced Neuronal Injury by Scavenging Free Radicals and Modulating NF-κB and JNK Pathways

Oxidative stress plays an important role in the pathological processes of ischemic brain damage. Many antioxidants have been shown to protect against cerebral ischemia injury by inhibiting oxidative stress both in vitro and in vivo. 20-Hydroxyecdysone (20E), an ecdysteroid hormone, exhibits antioxidative effects. For the work described in this paper, we used an in vitro oxidative damage model and an in vivo ischemic model of middle cerebral artery occlusion (MCAO) to investigate the neuroprotective effects of 20E and the mechanisms related to these effects. Treatment of cells with H₂O₂ led to neuronal injury, intracellular ROS/RNS generation, mitochondrial membrane potential dissipation, cellular antioxidant potential descent, an increase in malondialdehyde (MDA) and an elevation of intracellular [Ca²⁺], all of which were markedly attenuated by 20E. Inhibition of the activation of the ASK1-MKK4/7-JNK stress signaling pathway and cleaved caspase-3 induced by oxidative stress were involved in the neuroprotection afforded by 20E. In addition, 20E reduced the expression of iNOS protein by inhibition of NF-κB activation. The neuroprotective effect of 20E was also confirmed in vivo. 20E significantly decreased infarct volume and the neurological deficit score, restored antioxidant potential and inhibited the increase in MDA and TUNEL-positive and cleaved caspase-3-positive cells in the cerebral cortex in MCAO rats. Together, these results support that 20E protects against cerebral ischemia injury by inhibiting ROS/RNS production and modulating oxidative stress-induced signal transduction pathways.     

The effect of tea consumption on oxidative stress in smokers and nonsmokers

While the anticarcinogenic effects of tea in animal models have been reported by several groups, human epidemiological studies examining tea consumption and cancer prevention have produced equivocal results. The beneficial properties of tea to human health may be related to the antioxidant properties of tea components. However, little evidence has been provided that tea consumption can either increase the antioxidant capacity or decrease oxidative stress in humans. In the present study, the effects of tea treatment (green tea) on biomarkers of oxidative stress were investigated in smokers and nonsmokers in two volunteer study groups (one in China and the other in United States). Green tea consumption in both study groups decreased oxidative DNA damage (8-OHdG in white blood cells and urine), lipid peroxidation (MDA in urine), and free radical generation (2, 3-DHBA in urine) in smokers. Nonsmokers (US study group) also exhibited a decrease in overall oxidative stress.     

Experimental hyperthyroidism-induced oxidative stress and impairment of antioxidant defence system in rat testis

Short-term hyperthyroidism, induced by daily administration of T3 (20 microg/100g body weight) for one, three, and five days consecutively, modulates oxidative stress and antioxidant defence parameters in mitochondrial and postmitochondrial fractions of testis in adult rats. Alteration in antioxidant defences along with oxidative stress parameters in testis by thyroid hormone was found to be associated with a decline in the number of sperms and disturbances in histoarchitecture of seminiferous tubules in the testes; the results indicated that induced hyperthyroid state altered testicular physiology by influencing antioxidant defence system of testes.     

Hydroxytyrosol protects retinal pigment epithelial cells from acrolein-induced oxidative stress and mitochondrial dysfunction

Hydroxytyrosol (HTS) is a natural polyphenol abundant in olive oil. Increasing evidence indicates HTS has beneficial effect on human health for preventing various diseases. In the present study, we investigated the protective effects of HTS on acrolein-induced toxicity in human retinal pigment epithelial cell line, ARPE-19, a cellular model of smoking- and age-related macular degeneration. Acrolein, a major component of the gas phase cigarette smoke and also a product of lipid peroxidation in vivo , at 75 μmol/L for 24 h caused significant loss of cell viability, oxidative damage (increase in oxidant generation and oxidative damage to proteins and DNA, decrease in antioxidants and antioxidant enzymes, and also inactivation of the Keap1/Nrf2 pathway), and mitochondrial dysfunction (decrease in membrane potential, activities of mitochondrial complexes, viable mitochondria, oxygen consumption, and factors for mitochondrial biogenesis, and increase in calcium). Pre-treatment with HTS dose dependently and also time dependently protected the ARPE-19 cells from acrolein-induced oxidative damage and mitochondrial dysfunction. A short-term pre-treatment with HTS (48 h) required > 75 μmol/L for showing protection while a long-term pre-treatment (7 days) showed protective effect from 5 μmol/L on. The protective effect of HTS in this model was as potent as that of established mitochondria-targeting antioxidant nutrients. These results suggest that HTS is also a mitochondrial-targeting antioxidant nutrient and that dietary administration of HTS may be an effective measure in reducing and or preventing cigarette smoke-induced or age-related retinal pigment epithelial degeneration, such as age-associated macular degeneration.     

Carbon Monoxide： A Novel Antioxidant Against Oxidative Stress in Wheat Seedling Leaves

Carbon monoxide （CO）, an endogenous signaling molecule in animals, also provides potent cytoprotective effects including attenuation of lung lipid peroxidation induced by oxidant in the mouse. Our recent work demonstrated that 0.01 μmol/L hematin （a CO donor） treatment of wheat plants alleviated salt-induced oxidative damage in seedling leaves. In this report, we further discovered that hematin pretreatment （≤ 0.1 μmol/L） could delay wheat leaf chlorophyll loss mediated by further treatment of H202 and paraquat, two reactive oxygen species （ROS） sources, in dose-and even time-dependent manners. Also, compared with the control samples, seedling leaves pretreated with 0.01 or 0.1 μmol/L hematin for 24 h exhibited lower levels of H2O2 and lipid peroxidation, as well as higher contents of chlorophyll and activities of antioxidant enzymes. Such beneficial effects exerted by hematin were mimicked by the pretreatment of antioxidant butylated hydroxytoluene （BHT）, and differentially reversed when CO scavenger hemoglobin （Hb）, or CO specific synthetic inhibitor ZnPPIX was added, respectively. Taken together, the results presented In this paper directly illustrate for the first time that CO is able to strongly protect plants from oxidative damage caused by the overproduction of ROS, and strengthens the evidence that CO is a potent antioxidant in various abiotic and biotic stresses, as similar results have been shown in animal tissues.