Protective effect of quercetin on experimental chronic cadmium nephrotoxicity in rats is based on its antioxidant properties

Oxidative stress can play a key role in Cd-induced dysfunctions. Quercetin is a potent oxygen free radicals scavenger and a metal chelator. Our aim was to study the effect of quercetin on Cd-induced kidney damage and oxidative stress as well as its mechanism of action. Wistar rats were distributed in four experimental groups: control rats; Cd; quercetin and Cd + quercetin. Renal toxicity was evaluated by measuring urinary excretion of proteins, albumin, glucose and enzymes markers of tubular necrosis, as well as plasma concentration of creatinine. Plasma TBARS concentration and activity of antioxidant enzymes in kidney were also measured. Renal cell damage was assessed by electron microscopy. Animals that received both Cd and quercetin showed a better renal function than those receiving Cd alone. Cd-induced tubular lesions were markedly reduced in rats that also received quercetin. Cd-induced increase in plasma TBARS was prevented by the administration of quercetin. Total plasma antioxidants and renal superoxide dismutase and glutathione-reductase activities were higher in the group that received Cd and quercetin than in rats that received Cd alone. Quercetin administration does not modify the renal content or the urinary excretion of Cd. In conclusion, quercetin treatment prevents renal tubular damage and increased oxidative stress induced by chronic Cd administration, most probably throughout its antioxidant properties.     

COPD患者氧化剂损伤与抗氧化治疗的研究进展

氧化剂可致肺部氧化一抗氧化失衡，这是慢性阻塞性肺疾病（COPD）的重要发病机制之一，针对COPD的抗氧化治疗正日益受到重视。本文就其氧化剂损伤和抗氧化治疗的研究进展做一综述。     

鸡枞菌在大鼠高胆固醇血症中的抗氧化作用

目的观察云南野生鸡枞菌在高胆固醇血症大鼠中的抗氧化作用.方法雄性SD大鼠40只分设鸡枞菌高、低两个剂量组和高胆固醇模型组及正常对照组,前3个组给予高脂饲料喂养,并每日分组灌胃给6.25%、3.13%云南野生鸡枞菌匀浆液和蒸馏水10 ml/kg体重,连续30 d.分别测定血清总胆固醇(TC)及抗氧化指标.结果鸡枞菌高、低剂量组能显著降低高胆固醇血症大鼠血清中的MDA含量(P＜0.05,P＜0.01),提高SOD活力(P＜0.01).同时显著降低肝组织中MDA含量(P＜0.01).结论云南野生鸡枞菌对高胆固醇血症大鼠有明显的抗氧化作用.     

Modulation of oxidative stress-induced changes in hypertension and atherosclerosis by antioxidants

An imbalance between reactive oxygen species and antioxidant reserve, referred to as oxidative stress, results in the altered structure and function of proteins, lipids and DNA. Oxidative stress is associated with hypertension and atherosclerosis, but it is unknown whether it is a causative or resultant factor. The authors suggest that insulin resistance is the key element in the pathogenesis of these diseases, and leads to abnormal glucose and lipid metabolism with an increase in reactive aldehydes. These aldehydes react with the sulfhydryl and amino groups of proteins to form advanced glycation end products, adversely affecting body proteins, including antioxidant enzymes. This leads to oxidative stress. Advanced glycation end products and reactive oxygen species perpetuate a pro-oxidant state, producing the changes that are characteristic of hypertension and atherosclerosis. Antioxidants have been shown to modulate these changes. An ideal therapy for these diseases includes antioxidants, which attenuate insulin resistance, the source of oxidative stress.     

Effects of prenatal vitamins A, E, and C on the hypoplastic hearts of fetal rats with diaphragmatic hernia

Background/Aim

Nitrofen induces heart hypoplasia together with congenital diaphragmatic hernia (CDH) in rats. Intracellular oxidative stress might be one of the mechanisms of action of the teratogen, and vitamin A has been shown to reverse in part these effects when administered simultaneously or shortly after it. This study aims at testing the hypothesis that vitamin A and other antioxidant vitamins, such as E and C, could improve myocardial development even when administered late in gestation, a likely useful period for prenatal medication.

Material and Methods

Time-mated Sprague-Dawley female rats were exposed to either vehicle (control) or 100 mg of nitrofen (experimental) on day 9.5 of gestation. In 3 additional groups, the animals were exposed to vitamin A (total 15 000 IU), vitamin E (total 150 IU), or vitamin C (total 150 IU) on days 16, 17, and 18. The fetuses were recovered on day 21, and randomly selected hearts of those with CDH were processed for histologic studies (hematoxylin-eosin and periodic acid-Schiff stainings), DNA and protein contents, and ki-67 (proliferation) and terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling (apoptosis) studies. The differences among groups were assessed by analysis of variance with Bonferroni/Dunn post hoc tests and a threshold of significance of P < .05.

Results

Nitrofen induced heart hypoplasia in terms of decreased heart/body weight, cell mass (less DNA and protein), and proportion of proliferating cells with increased apoptosis. Vitamin C alleviated weight hypoplasia and the 3 vitamins were able to restore cell mass and to reestablish near-normal figures of proliferation and apoptosis.

Conclusions

Antioxidant vitamins A, E, and C given late in gestation alleviate heart hypoplasia that accompanies CDH in the rat model. This timing suggests that the beneficial effects are exerted on the maturational phase of development.     

Differential effect of gamma-radiation-induced heme oxygenase-1 activity in female and male C57BL/6 mice

Ionizing radiation produces reactive oxygen species, which exert diverse biological effects on cells and animals. We investigated alterations of heme oxygenase (HO) and non-protein thiols (NPSH), which are known as two major anti-oxidant enzymes, in female and male C57BL/6 mice in the lung, liver, and brain after whole-body gamma-irradiation with 10 Gy (1-7 days) as well as in the lung after whole-thorax gamma-irradiation (WTI) with 12.5 Gy (1-26 weeks). Most significant alteration of HO activity was observed in the liver, which elevated 250% in males. NPSH level in female liver was increased on the 5th-7th days but decreased in males on the 3rd day. In the lung, the elevation of HO activity in both sexes and the pattern of NPSH change were similar to that of the liver. On the other hand, the increase of HO activity on the 16th week and the decrease of NPSH level on the 2nd week were observed only in male lung after WTI. This study shows that the liver is the most sensitive tissue to gamma-irradiation-induced alterations of HO activity in both female and male mice. In addition, there exists significant differential effect of gamma-irradiation on anti-oxidant system in female and male mice.     

Antioxidant vitamins and lipid peroxidation in patients with cervical intraepithelial neoplasia

The purpose of this study was to investigate the implications of dietary intake and the level of plasma antioxidant, lipid peroxidation, and antioxidant capacity in Korean women with cervical intraepithelial neoplasia (CIN). From October 2002 to March 2003, 58 patients diagnosed with CIN (confirmed with colposcopy directed biopsy) and 86 patients without any cervical disease as control group were enrolled in the study at the Department of Gynecology cancer center at Samsung Cheil Hospital. The intake of antioxidant vitamins in both groups exceeded the amount recommended by the Korea RDA, 7th edition. The plasma concentration of Vitamin C was significantly lower in the CIN group (0.36 mg/dL) than in the control group (0.48 mg/dL) (p<0.05). The two groups showed similar plasma concentrations of beta-carotene, alpha-tocopherol, and retinol. The average concentration of malondialdehydes in the CIN group, 7.23 mmol/mL, was significantly higher than in the control group, 5.18 mmol/mL (p<0.01). The total radical trapping antioxidant potential concentration of plasma was significantly higher in the CIN group (1.15 mM) than in the control group (1.25 mM) (p<0.05). These results suggest that there is a possible correlation between cervical intraepithelial neoplastic processes and changes in the plasma antioxidative system.     

Antioxidants do not explain the disparate longevity between mice and the longest-living rodent, the naked mole-rat

The maximum lifespan of naked mole-rats (NMRs; Heterocephalus glaber) is greater than that of any other rodent. These hystricognaths survive in captivity >28 years, eight-times longer than similar-sized mice. The present study tested if NMRs possess superior antioxidant defenses compared to mice and if age-related interspecies changes in antioxidants were evident. Activities of Cu/Zn superoxide dismutase (Cu/Zn, SOD), Mn SOD, catalase and cellular glutathione peroxidase (cGPx) were measured in livers of physiologically equivalent age-matched NMRs (30, 75 and 130 months) and CB6F1 mice (4, 12 and 18 months). In mice, Mn SOD activity increased with age, while the activity of catalase and cGPx declined. None of the antioxidants changed with age in mole-rats. cGPx activity of NMRs was 70-times lower (p < 0.0001) than in mice, and resembled that of cGPx knock-out animals. NMRs may partially compensate for the lower cGPx when compared to mice, by having moderately higher activities of the other antioxidants. It is nonetheless unlikely that antioxidant defenses are responsible for the eight-fold longevity difference between these two species. Maintenance of constant antioxidant defenses with age in NMRs concurs with previous physiological data, suggesting delayed aging in this species.     

Improved psychomotor performance in aged mice fed diet high in antioxidants is associated with reduced ex vivo brain interleukin-6 production

Psychomotor performance is decreased in the aged. This study investigated the relationship between brain oxidative stress, interleukin-6 (IL-6) production by brain tissue ex vivo and psychomotor deficits during aging, and the effects of feeding an antioxidant-rich diet on ex vivo brain IL-6 production and motor function in aged mice. Male BALBc mice reared in SPF conditions and ranging in age from 3 to 24 months were studied. There was a precipitous decline in motor function after 12 months of age and an increase in brain lipid peroxidation and IL-6 production by coronal brain slices ex vivo. In another study, 12-month-old mice were fed diets formulated to provide a disparate range of antioxidants. At 18 months of age psychomotor coordination, motor learning, and ex vivo brain IL-6 production were evaluated. Mice fed an antioxidant-rich diet had improved psychomotor coordination compared to mice fed diet adequate or low in antioxidants. When mice were tested on successive days, only those fed adequate and high antioxidants exhibited motor learning. Analysis of IL-6 production by coronal brain slices indicated that as dietary antioxidants increased, IL-6 production decreased. Collectively, these data indicate that antioxidants improve psychomotor performance in aged mice, and suggest antioxidants may be useful for reducing brain IL-6 production, which has been shown to increase in aged mice.     

Antioxidative vitamins decrease cytotoxicity of HEMA and TEGDMA in cultured cell lines

OBJECTIVES AND METHODS: In a previous study it was postulated that toxicity of 2-hydroxyethylmethacrylate (HEMA) and triethleneglycoldimethacrylate (TEGDMA) is based on oxidative metabolites. In this study the influence of antioxidative vitamins (including uric acid) on the toxicity of HEMA or TEGDMA was tested. Toxicity of HEMA and TEGDMA was determined in rat alveolar epithelial L2, human malignant A549, and human fibroblast-like 11Lu cells by inhibition of methionine incorporation (as a marker of protein synthesis inhibition) and by determination of glutathione depletion, as well as by measurement of GSSG increase. RESULTS: Toxicity of the composite components HEMA and TEGDMA was demonstrated by GSH depletion as the most sensitive method. Five hundred micromoles per litre Vitamin C or 250 micromol/l Vitamin E were mostly able to decrease toxicity of HEMA and TEGDMA in the cell lines tested. In addition, 250 micromol/l Vitamin A was only effective in L2 cells impairing HEMA toxicity and 250 micromol/l uric acid impairing TEGDMA toxicity as assessed by decreased GSH depletion. In A549 cells only methionine incorporation inhibition but not GSH depletion was significantly affected. By contrast, in 11Lu cells methionine incorporation inhibition was not significantly changed, but GSH depletion was. CONCLUSIONS: The postulated mechanism of HEMA or TEGDMA toxicity based on radical metabolites is supported by the effectivity of the antioxidative substances tested in mitigating toxicity and by the greater susceptibility of the glutathione redox system as compared to protein synthesis inhibition in assessing toxicity.