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.     

Oxidative stress decreases antioxidant enzyme activities in reaggregation cultures of rat brain cells

The brain has been suggested to be especially sensitive to damage by reactive oxygen species. In this study, we examined the effects of hyperoxic conditions on the activities and mRNA levels of antioxidant enzymes in reaggregation cultures of rat forebrain cells. Cultures were exposed to 80% oxygen for 12–60 h starting on Days 17 and 33 in culture. Superoxide dismutase activities and mRNA levels were not affected by hyperoxia, whereas catalase activity was slightly decreased after 24 h in 80% oxygen at Day 17. Glutathione peroxidase activity was markedly decreased already after 12 h of hyperoxia, and decreased activities of glutathione reductase and glucose-6-phosphate dehydrogenase were also noted. The glutathione peroxidase mRNA levels were increased in hyperoxic cultures at Day 17 but not at Day 33. These results suggest that the enzymatic defense mechanisms against reactive oxygen species in the brain are rather weak and deteriorate during oxidative stress but that a potential for compensatory upregulation exists at least during the first postnatal weeks.     

Differential response of the antioxidant system in wild and cultivated genotypes of chickpea

Two chickpea cultivars PBG-1 and PDG-3 along with a wild species Cicer judaicum were investigated to compare the activities of their antioxidant enzymes in mature seeds and roots, as well as shoots and cotyledons of seedlings germinated under dark and continuous illumination of 40 μmol m⁻² s⁻¹ photosynthetically active radiation (PAR). Seedling biomass of C. judaicum was lower as compared to cultivars of PBG-1 and PDG-3 both under dark and light conditions. Light reduced the biomass of seedlings. Activities of glutathione reductase (GR) and ascorbate peroxidase (APX) were higher in shoots and roots of C. judaicum compared to the cultivars PBG-1 and PDG-3. In mature seeds, the activities of GR and APX were higher in the cultivated genotypes whereas catalase (CAT) and peroxidase were higher in C. judaicum. Under illumination, a general upregulation of CAT in both shoots and cotyledons and of GR in shoots was observed in all the three genotypes. However, superoxide dismutase (SOD) increased in C. judaicum and APX in PBG-1 and PDG-3. The differences in antioxidant enzyme system between wild and cultivated genotypes possibly contribute to better tolerance of wild Cicer species against abiotic and biotic stresses.     

The pro-oxidant role of protein SH groups of hemoglobin in rat erythrocytes exposed to menadione.

Menadione is selectively toxic to erythrocytes. Although GSH is considered a primary target of menadione, intraerythrocyte thiolic alterations consequent to menadione exposure are only partially known. In this study alterations of GSH and protein thiols (PSH) and their relationship with methemoglobin formation were investigated in human and rat red blood cells (RBC) exposed to menadione. In both erythrocyte types, menadione caused a marked increase in methemoglobin associated with GSH depletion and increased oxygen consumption. However, in human RBC, GSH formed a conjugate with menadione, whereas, in rat RBC it was converted to GSSG, concomitantly with a loss of protein thiols (corresponding to menadione arylation), and an increase in glutathione-protein mixed disulfides (GS-SP). Such differences were related to the presence of highly reactive cysteines, which characterize rat hemoglobin (cys beta125). In spite of the greater thiol oxidation in rat than in human RBC, methemoglobin formation and the rate of oxygen consumption elicited by menadione in both species were rather similar. Moreover, in repeated experiments under N2 or CO-blocked heme, it was found that menadione conjugation (arylation) in both species was not dependent on the presence of oxygen or the status of heme. Therefore, we assumed that GSH (human RBC) and protein (rat RBC) arylation was equally responsible for increased oxygen consumption and Hb oxidation. Moreover, thiol oxidation of rat RBC was strictly related to methemoglobin formation.     

The effect of menadione-induced oxidative stress on the in vivo reactive oxygen species and antioxidant response system of Phanerochaete chrysosporium

The antioxidant response system of Phanerochaete chrysosporium against menadione-induced oxidative stress was investigated in this study. The superoxide anion radical levels in tested menadione-supplemented conditions generally decreased over the incubation period. The level of hydrogen peroxide and the activities of NAD(P)H oxidase, superoxide dismutase (SOD) and catalase (CAT) were higher than those in the controls at all incubation times. The highest NADH and NADPH oxidase activities were determined to be 4.9- and 5.0-fold higher than those in the control, respectively in cells exposed to 0.75 mM menadione. The SOD and CAT activities increased with increasing menadione, and their highest activities were 5.4- and 5.1-fold higher than those in the control, respectively. In 0.1–0.5 mM menadione exposed cells, the lipid peroxidation levels did not change significantly when compared to each other, except 8th hour of incubation (p > 0.01). Our result shows that although menadione induces the formation of reactive oxygen species, the antioxidant response system of P. Chrysosporium is able to negate menadione-induced oxidative stress up to relatively high menadione concentrations, as 0.75 mM. These results are important to determine the effects of menadione, as a medicine, on the antioxidant response system of eukaryotic models and the resulting level of damage.     

Effect of cryopreservation on sperm parameters, lipid peroxidation and antioxidant enzymes activity in fowl semen

The aim of the present study was to determine the influence of chicken semen cryopreservation on sperm parameters, lipid peroxidation and antioxidant enzymes activities. Pooled semen from 10 Black Minorca roosters was used in the study. Semen samples were subjected to cryopreservation using the “pellet” method and dimethylacetamide (DMA) as a cryoprotectant. In the fresh and the frozen-thawed semen sperm membrane integrity (SYBR-14/propidium iodide (PI)), acrosomal damage (PNA-Alexa Fluor^®488) and mitochondrial activity (Rhodamine 123) were assessed using flow cytometry. Malondialdehyde (MDA) concentration, catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were determined in sperm cells and seminal plasma by spectrophotometry. All sperm characteristics evaluated using flow cytometry were affected by cryopreservation. After freezing-thawing, there was significant (P < 0.01) reduction in sperm membrane integrity, sperm acrosome integrity and mitochondrial activity. Following cryopreservation, MDA concentration significantly increased in chicken seminal plasma and spermatozoa (P < 0.01, P < 0.05). The CAT activity in seminal plasma significantly decreased (P < 0.05), while intracellular activity of this enzyme did not significantly change in frozen-thawed semen. In seminal plasma of frozen-thawed semen the significant increase (P < 0.01) in GPx activity was detected. Whereas GPx activity in spermatozoa remained statistically unchanged after thawing. The SOD activity significantly increased (P < 0.01) in cryopreserved seminal plasma with simultaneous decrease (P < 0.01) of its activity in cells. In conclusion, this is probably the first report describing the level of antioxidant enzymes in frozen-thawed avian semen. The present study showed that the activity of CAT, GPx and SOD in chicken semen was affected by cryopreservation, what increased the intensity of lipid peroxidation (LPO). Catalase appeared to play an important role in the sperm antioxidant defense strategy at cryopreservation since, opposite to SOD and GPx, its content was clearly reduced by the cryopreservation process. Change in the antioxidant defense status of the chicken spermatozoa and surrounding seminal plasma might affect the semen quality and sperm fertilizing ability.     

Weak antioxidant defenses make the heart a target for damage in copper-deficient rats

Copper deficiency causes more salient pathologic changes in the heart than in the liver of rats. Although oxidative stress has been implicated in copper deficiency-induced pathogenesis, little is known about the selective toxicity to the heart. Therefore, we examined the relationship between the severity of copper deficiency-induced oxidative damage and the capacity of antioxidant defense in heart and liver to investigate a possible mechanism for the selective cardiotoxicity. Weanling rats were fed a purified diet deficient in copper (0.4 μg/g diet) or one containing adequate copper (6.0 μg/g diet) for 4 weeks. Copper deficiency induced a 2-fold increase in lipid peroxidation in the heart (thiobarbituric assay) but did not alter peroxidation in the liver. The antioxidant enzymatic activities of superoxide dismutase, catalase, and glutathione peroxidase were, respectively, 3-, 50- and 1.5-fold lower in the heart than in the liver, although these enzymatic activities were depressed in both organs by copper deficiency. In addition, the activity of glutathione reductase was 4 times lower in the heart than in the liver. The data suggest that a weak antioxidant defense system in the heart is responsible for the relatively high degree of oxidative damage in copper-deficient hearts.     

动物抗氧化系统中主要抗氧化酶基因的研究进展

抗氧化系统是机体清除体内多余的活性氧、保护自身免受氧化损伤的重要体系,其中超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶等起主要作用。本文将对动物抗氧化系统中,超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶基因的种类、分布、结构及表达进行综述。     

Autoxidation of extracellular hydroquinones is a causative event for the cytotoxicity of menadione and DMNQ in A549-S cells

Cytotoxicity of 1,4-naphthoquinones has been attributed to intracellular reactive oxygen species (ROS) generation through one-electron-reductase-mediated redox cycling and to arylation of cellular nucleophiles. Here, however, we report that in a subclone of lung epithelial A549 cells (A549-S previously called A549-G4S (Watanabe, et al., Am. J. Physiol. 283 (2002) L726-736), the mechanism of ROS generation by menadione and by 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), and therefore that of cytotoxicity, differs from the paradigm. Ninety percent of H(2)O(2) generation by both the quinones can be prevented by dicumarol, an inhibitor of NAD(P)H quinone oxidoreductase (NQO1), at the submicromolar level, regardless of the quinone concentrations. Exogenous SOD also inhibits H(2)O(2) production at low but not high concentrations of the quinones, especially DMNQ. Thus, at low quinone concentrations, superoxide-driven hydroquinone autoxidation accounts for more than half of H(2)O(2) generation by both quinones, whereas at high quinone concentrations, especially for DMNQ, comproportionation-driven hydroquinone autoxidation becomes the predominant mechanism. Hydroquinone autoxidation appears to occur predominantly in the extracellular environment than in the cytosol as extracellular catalase can dramatically attenuate quinone-induced cytotoxicity throughout the range of quinone concentrations, whereas complete inactivation of endogenous catalase or complete depletion of intracellular glutathione has only a marginal effect on their cytotoxicity. Finally, we show evidence that ROS production is a consequence of the compensatory defensive role of NQO1 against quinone arylation.     

Induction of peroxide and superoxide protective enzymes and physiological cross-protection against peroxide killing by a superoxide generator in Vibrio harveyi

Vibrio harveyi is a causative agent of destructive luminous vibriosis in farmed black tiger prawn (Penaeus monodon). V. harveyi peroxide and superoxide stress responses toward elevated levels of a superoxide generated by menadione were investigated. Exposure of V. harveyi to sub-lethal concentrations of menadione induced high expression of genes in both the OxyR regulon (e.g., a monofunctional catalase or KatA and an alkyl hydroperoxide reductase subunit C or AhpC), and the SoxRS regulon (e.g., a superoxide dismutase (SOD) and a glucose-6-phosphate dehydrogenase). V. harveyi expressed two detectable, differentially regulated SOD isozymes, [Mn]-SOD and [Fe]-SOD. [Fe]-SOD was expressed constitutively throughout the growth phase while [Mn]-SOD was expressed at the stationary phase and could be induced by a superoxide generator. Physiologically, pre-treatment of V. harveyi with menadione induced cross-protection against subsequent exposure to killing concentrations of H(2)O(2). This induced cross-protection required newly synthesized proteins. However, the treatment did not induce significant protection against exposures to killing concentrations of menadione itself or cross-protect against an organic hydroperoxide (tert-butyl hydroperoxide). Unexpectedly, growing V. harveyi in high-salinity media induced protection against menadione killing. This protection was independent of SOD induction. Stationary-phase cells were more resistant to menadione killing than exponential-phase cells. The induction of oxidative stress protective enzymes and stress-altered physiological responses could play a role in the survival of this bacterium in the host marine crustaceans.     

Enhanced tolerance to oxidative stress in transgenic tobacco plants expressing three antioxidant enzymes in chloroplasts

The effect of simultaneous expression of genes encoding three antioxidant enzymes, copper zinc superoxide dismutase (CuZnSOD, EC 1.15.1.1), ascorbate peroxidase (APX, EC 1.11.1.11), and dehydroascorbate (DHA) reductase (DHAR, EC 1.8.5.1), in the chloroplasts of tobacco plants was investigated under oxidative stress conditions. In previous studies, transgenic tobacco plants expressing both CuZnSOD and APX in chloroplast (CA plants), or DHAR in chloroplast showed enhanced tolerance to oxidative stresses, such as paraquat and salt. In this study, in order to develop transgenic plants that were more resistant to oxidative stress, we introduced the gene encoding DHAR into CA transgenic plants. Mature leaves of transgenic plants expressing all three antioxidant genes (CAD plants) had approximately 1.6–2.1 times higher DHAR activity, and higher ratios of reduced ascorbate (AsA) to DHA, and oxidized glutathione (GSSG) to reduced glutathione (GSH) compared to CA plants. CAD plants were more resistant to paraquat-induced stress, exhibiting only 18.1% reduction in membrane damage relative to CA plants. In addition, seedlings of CAD plants had enhanced tolerance to NaCI (100 mM) compared to CA plants. These results indicate that the simultaneous expression of multiple antioxidant enzymes, such as CuZnSOD, APX, and DHAR, in chloroplasts is more effective than single or double expression for developing transgenic plants with enhanced tolerance to multiple environmental stresses.     

Variation in heat stress-induced antioxidant enzyme activities among three mulberry cultivars

The effects of high temperature on antioxidant enzymes were investigatedin three mulberry (Morus alba L.) cultivars (cv. K-2, MR-2and BC2-59). High temperature was imposed by maintaining the plants at 40°Cfor 120, 240 and 360 min in an environmentalplant growth chamber.The activities of superoxide disumutase (SOD), catalase (CAT), guaiacolperoxidase (POD), ascorbate peroxidase (APX) and glutathione reductase (GR)wereassayed in the leaf extracts of control and high temperature-treated plants.Antioxidant enzyme activities were high in all the mulberry cultivars inresponse to high temperature treatment. However, cv. BC2-59 showedsignificantlyhigher activities of all the five antioxidant enzymes in response to hightemperature compared to those from the leaves of K-2, and MR-2 mulberrycultivars. The present study suggested that the cv. BC2-59 has an efficientantioxidant system among the three cultivars, which could prevent the oxidativedamage in the leaves caused by high temperature stress.     

不同剂量白藜芦醇对糖尿病性白内障大鼠晶状体抗氧化酶活力的影响

目的:探究不同剂量白藜芦醇对糖尿病性白内障大鼠晶状体抗氧化酶活力的影响。方法:75只5周龄健康SPF级雄性SD大鼠按照随机数字表法分为正常对照组、模型组,白藜芦醇低剂量组,白藜芦醇中剂量组和白藜芦醇高剂量组,每组各15只。五组大鼠均给予常规适应性喂养,模型组和白藜芦醇低、中、高剂量组大鼠采用链脲佐菌素(STZ)以60 mg/kg的给药剂量制作糖尿病大鼠模型,成模后白藜芦醇低剂量组按20 mg/kg、白藜芦醇中剂量组按50 mg/kg、白藜芦醇高剂量组按100 mg/kg的给药剂量每日给予白藜芦醇灌胃。观察12周后5组大鼠晶状体的混浊程度,检测血糖、体重后处死大鼠,检测晶状体内超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)以及过氧化氢酶(CAT)的活性改变。结果:随着白藜芦醇剂量的升高,白藜芦醇低、中、高剂量组大鼠的血糖逐渐降低而体重逐渐升高,且组间比较均具有统计学差异(P0.05)。三组不同剂量白藜芦醇干预组大鼠晶状体的浑浊程度均低于模型组,且白藜芦醇高剂量组大鼠晶状体的浑浊程度最低,差异均具有统计学意义(P0.05)。白藜芦醇低、中、高剂量组大鼠SOD、GSH-PX和CAT酶活力与模型组大鼠相比均明显升高,而与正常对照组相比均明显降低(均P0.05)。随着白藜芦醇剂量的升高,白藜芦醇低、中、高剂量组大鼠SOD、GSH-PX和CAT酶活力逐渐升高,且组间比较均具有统计学差异(P0.05)。结论:高剂量白藜芦醇可更为明显地降低血糖浓度,提高晶状体SOD、GSH-Px及CAT酶活力,改善糖尿病性白内障晶状体的浑浊程度。     

Pair-wise linear and 3D nonlinear relationships between the liver antioxidant enzyme activities and the rate of body oxygen consumption in mice

Relationships between the rate of body oxygen consumption (VO₂) and the liver key antioxidant enzyme activities were assessed in female CBA mice. The pair-wise linear regression and correlation demonstrated significant correlative links between VO₂ and activity of catalase (CAT). Nonlinear 3D plotting revealed a complementary pattern of CAT and glutathione peroxidase (GP) relation. CAT activity was elevated in mice with proportionally high VO₂ and superoxide dismutase (SOD), whereas GP activity was high in animals with low or disproportional VO₂ and SOD.     

Alterations in Protective Enzymes Against Peroxidation in the Central and Peripheral Nervous System of Control and Dysmyelinating Mutant Mice

The activities of peroxide-detoxifying enzymes such as superoxide dismutase (SOD), glutathione peroxidase, glutathione reductase, and catalase were measured in the nervous system of neurological dysmyelinating mutants: quaking (Qk), shiverer (Shi), and trembler (Tr) mice. Cu/Zn-SOD activity was higher in the cerebellum of Qk and Shi mice (by 53% and 106%, respectively) in comparison with controls, but it was the same in the cerebellum of Tr mice and their corresponding controls. In contrast, there was no difference in the level of Cu/Zn-SOD activity in the cerebrum of Qk, Shi, and Tr mice and their respective controls. Mn-SOD activity was the same among all the mutants compared to control animals in both cerebrum and cerebellum. In Shi cerebellum, glutathione peroxidase and glutathione reductase activities were slightly decreased (a 21.6% and a 13.2% diminution, respectively), whereas catalase activity in cerebrum and cerebellum was the same among mutants and control mice. In the sciatic nerve from Tr mice, all the enzymatic activities were enhanced: sixfold increase for total SOD, and 2.4-fold, 3.5-fold, and 1.8-fold increase for glutathione peroxidase, glutathione reductase, and catalase, respectively.     

Lipid Peroxidation and Antioxidant Enzyme Activities in Vascular and Alzheimer Dementias

It has been reported that oxidative stress may play a role in the pathogenesis of dementia of the Alzheimer type (AD) and the cerebral ischemia which causes vascular dementia (VD). We measured malondialdehyde (MDA) levels and superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) activities in blood samples from patients with AD and VD and in healthy non-demented controls (CTR) which similar ages to the patients, in order to evaluate the degree of oxidative stress in patients with AD and VD. A sample of 150 subjects consisting of 50 patients with AD; 50 patients with VD and 50 CTR, aged from 65 to 85 years on, was analyzed. Most of the changes observed were in SOD activity and MDA levels. Catalase activity were least affected. Significant differences were observed in SOD and GR activity between males and females in CRT and in patients with AD, but not in VD. We have found a decrease in antioxidant enzymes activities (SOD, CAT, GPx and GR) in patients with AD and VD and significant differences were observed between CRT and AD patients for ages from 65 to 74, 75 to 84 and from 85 years to 94 years in SOD activity and MDA levels (P < 0.001). MDA levels increase with age in VD, AD and CTR. No significant variation with respect to sex were detected, but significant variations in MDA levels were detected between CRT and patients with VD and AD (P < 0.001). We conclude that oxidative stress plays an important role in the brain damage for both AD and VD, being observed higher levels of oxidative stress for AD that for VD.     

Antioxidant enzymes in Spodoptera littoralis (Boisduval): are they enhanced to protect gut tissues during oxidative stress?

The Egyptian armyworm Spodoptera littoralis is a polyphagous insect attacking a number of plant species including those belonging to the Solanaceae and Cruciferaceae families. Its digestive physiology must therefore adapt to the food plant to ensure maximum extraction of nutrients with minimum trade-off in terms of growth retardation by pro-oxidant allelochemicals. To investigate this, the caterpillars of S. littoralis were fed on a semi-artificial diet (Manduca Premix-Heliothis Premix) and for 24 h on potato plants (Solanum tuberosum), respectively, at the mature 6th instar, and the levels of oxidative radicals and antioxidant enzymes in their guts were compared. The gut pH, standard redox potential (Eh) and electron availability (pe) revealed that oxidizing conditions prevail which promote oxidation of pro-oxidant allelochemicals in foliage. Oxidative stress in the foregut and midgut tissue and the gut contents was assessed from the generation of superoxide radical, total peroxide content and protein carbonyl content. Antioxidant defense was measured by the activities of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APOX) and glutathione S-transferase peroxidase (GSTpx). A significant (p < 0.001) increase in the superoxide radical production (in foregut tissue, foregut and midgut contents), concomitant with an increase in total peroxide (in foregut contents) and protein carbonyl levels (in foregut and midgut tissue) were noted in larvae fed on the plants in contrast to those fed the semi-artificial diet. Similarly, a significant up-regulation of antioxidant enzymes SOD (in midgut tissues), CAT (in foregut, midgut tissue and contents), APOX (in foregut contents, midgut tissue and contents) and GSTpx (in foregut tissues) was recorded on the plant diet in comparison to the semi-artificial diet. The pro-oxidant allelochemicals in the plant diet are thus eliminated by the insect at the expense of up-regulation of antioxidative enzymes in response to increased oxidative stress from oxidizable allelochemicals. The results are consistent with the hypothesis that increased concentrations of antioxidants form an important component of the defense of herbivorous insects against both exogenous and endogenous oxidative radicals.     

Species-related variations in antioxidant components of gastric and duodenal mucosa

Enzymatic and non-enzymatic antioxidant profiles of the gastric and duodenal mucosa of rat, rabbit, cat and pig were investigated and found to exhibit significant variations. Rat gastric and duodenal mucosa exhibited the highest levels of basal glutathione of the various tissues examined. The highest activity of glutathione reductase was found in the gastric and duodenal mucosa of rat as compared with that in these tissues from the other species. The gastric mucosa of cat and pig showed similar activities of glutathione peroxidase, which was significantly lower than those in rat or rabbit gastric mucosa. The activity of this antioxidant enzyme was similar in rat, rabbit and pig duodenal mucosa and lower than that in cat duodenal mucosa. Strong correlations were found between activities of the functionally coupled antioxidant enzymes glutathione peroxidase and glutathione reductase in gastric but not in duodenal mucosa. The activity of superoxide dismutase showed negligible regional or species-related variations in activity.     

Silymarin increases antioxidant enzymes in alloxan-induced diabetes in rat pancreas

The aim of this study was to analyze the effect of the flavonoid silymarin, a free radical scavenger that prevents lipoperoxidation, on the pancreatic activity of superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and catalase (CAT) in rats with alloxan-induced diabetes mellitus. Alloxan intoxicated rats were treated with silymarin in two manners, simultaneously (four or eight doses) or 20 days after alloxan administration for 9 weeks. Alloxan elicited a transient increase in the activity of the three enzymes, which decreased after 5 days of treatment. On its own, silymarin significantly increased the activity of these enzymes. Simultaneous treatment with alloxan and silymarin also induced an increment in the activity of the enzymes followed by a delayed decrease (four doses). However, a longer treatment with silymarin (eight doses) induced a more sustained effect. Interestingly, silymarin treatment recovered to control values for the activity of the three-antioxidant enzymes that were significantly diminished after 20 days of alloxan administration. It is suggested that the protective effect of silymarin on pancreatic damage induced by alloxan may be due to an increase in the activity of antioxidant enzymes that, in addition to the glutathione system, constitute the more important defense mechanisms against damage by free radicals.     

Molecular mechanisms of oxidative stress resistance induced by resveratrol: Specific and progressive induction of MnSOD

trans-Resveratrol (3,4′,5-trihydroxystilbene; RES), a polyphenol found in particularly high concentrations in red wine, has recently attracted intense interest for its potentially beneficial effects on human health. Here, we report the effects of long-term exposure to micromolar concentrations of RES on antioxidant and DNA repair enzyme activities in a human cell line (MRC-5). RES had either no effect on, or reduced the activities of glutathione peroxidase, catalase and CuZn superoxide dismutase (SOD), in treatments lasting up to 2 weeks. RES failed to induce activities of the DNA base excision repair enzymes apurinic/apyrimidinic endonuclease and DNA polymerase β. However, it dramatically and progressively induced mitochondrial MnSOD expression and activity. Two weeks exposure to RES increased MnSOD protein level 6-fold and activity 14-fold. Thus, long-term exposure of human cells to RES results in a highly specific upregulation of MnSOD, and this may be an important mechanism by which it elicits its effects in human cells.