Patterns of destruction of mouse neuroblastoma cells by extracellular hydrogen peroxide formed by 6-hydroxydopamine and ascorbate

Summary The patterns of the cytolytic effects of 6-hydroxydopamine (6-OHDA), with/without ascorbate, on C-1300 and three other cloned mouse neuroblastoma cell lines (N1E-115, NS-20, N-18) were studied in vitro. The sensitivity to 6-OHDA differed and the three cloned cell lines were more sensitive than the wild type C-1300 cell line. Ascorbate synergistically potentiated the cytolytic effect of 6-OHDA to all four cell lines. The 6-OHDA cytotoxicity was eliminated by the addition of exogenous catalase but not by addition of other oxygen free radical scavengers, thereby suggesting that the hydrogen peroxide formed might influence the cells, extracellularly. In addition, the critical time for tumor cell lysis was the first 60 min of the reaction. The cytotoxicity induced by the unmasked cyclophosphamide, 4-hydroperoxycyclophosphamide, was synergistically enhanced in the presence of a nontoxic concentration of 6-OHDA and ascorbate. These data suggest that reactive oxygen intermediates may prove to be a good tool for destroying neuroblastoma cells.     

克山病人心肌的自由基代谢

本实验测定了克山病死亡者心肌的自由基含量、脂质过氧化物水平及产生和清除自由基的主要酶(XOD 和 Cu-Zn SOD)的活性。结果表明,克山病人心肌中存在着自由基代谢的紊乱。表现为心肌 ESR 值及 TBA 值的增高和心肌 Cu-Zn SOD、XOD 活性的降低。本文还把克山病人体内自由基紊乱与克山病动物模型的上述紊乱的异同进行了比较,并进一步探讨了自由基损伤学说在克山病的病因学、发病学及防治工作中的重要作用。     

Effect of coadministration of parenteral multivitamins with lipid emulsion on lung remodeling in an animal model of total parenteral nutrition

Exposure of parenteral multivitamin solutions (MVP) to ambient light generates peroxides and vitamin loss, and induces initiation of fibrosis and a reduced alveolar count in an animal model of total parenteral nutrition (TPN). Adding MVP to the lipid moiety of TPN prevents lipid peroxidation and vitamin loss. The aim of the study was to compare modes of delivery of MVP on lung procollagen mRNA and alveolar counts. Three-day-old guinea pig pups were infused continuously with one of three intravenous solutions: 1) control = dextrose; 2) AA + MVP = MVP given with the dextrose + amino-acid moiety, in a "piggyback" setup with a lipid emulsion mixed close to the infusion site; and 3) LIP + MVP = same as AA + MVP, except that MVP is given with the lipid emulsion. After 4 days, lungs were prepared for alveolar count (intercept technique) and for quantification of the procollagen/beta-actin mRNA ratio (initial step of fibrosis). Data were compared by ANOVA. The procollagen mRNA was lower (P < 0.05) in animals receiving LIP + MVP than those with AA + MVP. But the two modes of admixture of MVP had the same effect on the alveolar counts, which were lower (P < 0.01) than controls. The mode of delivery of TPN affects lung remodeling. Although LIP + MVP protects against the initiation of lung fibrosis, the absence of a beneficial effect on alveolar counts suggests that these features of lung remodeling are not caused by a unique component of TPN. Specific roles of peroxides, components of MVP, and light exposure on lung remodeling need to be explored before LIP + MVP can be recommended as an alternative mode of parenteral vitamin delivery.     

Age-dependent production of mitochondrial hydrogen peroxide,lipid peroxides and fluorescent pigments in the rat heart

Summary Mitochondria were prepared from hearts of 3-, 14-, 18-, and 24-month-old male Wistar rats. Respiratory control ratio (RCR) values did not change with age in the glutamate or succinate-induced respiration except at 24 months in which RCR values significantly increased with both the substrates. Using still glutamate or succinate as substrates the production of H₂O₂ was measured in the presence of antimycin. A 70% and 25% increase in H₂O₂ formation was observed at 14 and 18 months of age, respectively, in comparison to the youngest group. Only in the presence of succinate was a 25% elevation in H₂O₂ found at 24 months of age. These observations parallel with the decrease of the ratio between tissue levels of reduced and oxidized glutathione that was observed at 14 and 18 months of age. The concentration of myocardial malondialdehyde, a secondary product of lipid peroxidation, remained the same at all ages measured, most probably because it is readly metabolized in vivo. On the contrary the myocardial level of lipofuscin, which is not degraded by the cell, progressively increased beginning from 18 months of age.     

Efficacy and safety of 2% supramolecular salicylic acid compared with 5% benzoyl peroxide/0.1% adapalene in the acne treatment: a randomized,split-face,open-label,single-center study

Background: Topical drugs for mild to moderate acne include adapalene (ADA) and benzoyl peroxide(BPO). Supramolecular salicylic acid (SSA), a modified SA preparation, is considered as a new effective therapeutic scheme.

Objectives: To compare the safety and efficacy of 2% supramolecular SA (2% SSA) with 0.01% adapalene plus 5% benzoyl peroxide (5%BPO +0.1%ADA) for treatment of facial acne.

Materials and methods: This was an open-label, split face, randomized and single-centre clinical trial. Subjects with mild to moderate acne were enrolled. Two percent SSA cream were randomly applied on one side of the face while 5%BPO +0.1%ADA gel was applied on the opposite side for 28?days. The numbers of acne lesions, along with side effects of the targeted area were evaluated by the investigators at day 0, day 14, and day 28. Skin water content, TEWL and skin lightening indexes were measured at the same time.

Results: A total of 31 of acne patients completed the trial. Dates showed that 2% SSA had similar effects to 5%BPO +0.1%ADA in reducing papules/pustules (47.9% vs. 49.8%), non-inflammatory lesions (43.1% vs. 42.7%) and total lesions (44.1% vs. 45.6%; all p?>?0.05) at day 28. The skin barrier (skin hydration value and TEWL value), skin brightness (L* value) and erythema (a* values) indicators showed no statistical differences in the left and right sides of the face (p?>?0.05).

Conclusion: This study demonstrated that 2% SSA has a similar efficacy with 5%BPO +0.1%ADA in mild to moderate acne treatment. This might be a useful pilot study that could be used to support further larger clinical trials.     

Biodegradable poly(vinyl alcohol)/polyoxalate electrospun nanofibers for hydrogen peroxide-triggered drug release

Release of drugs in a controlled and sustainable manner is of great interest for treating some inflammatory diseases, drug delivery, and cosmetics. In this work, we demonstrated the control release of a drug from composite nanofibers mediated by hydrogen peroxide. Composite nanofibers of polyvinyl alcohol (PVA)/polyoxalate (PVA/POX NFs) blended at various weight ratios were successfully prepared by electrospinning. Rhodamine B (RB) was used as a model of drug and was initially loaded into the POX portion. The morphology of NFs was characterized using scanning electron microscopy (SEM). The functional groups presented in the NFs were characterized using IR spectroscopy. In vitro release behavior and cell toxicity of nanofibers were also investigated using the MTT assay. The results indicated that POX content had a significant effect on the size and release profiles of nanofibers. Microstructure analysis revealed that sizes of PVA/POX NFs increased with increasing POX content, ranging from 214 to 422 nm. Release profiles of RB at 37 °C were non-linear and showed different release mechanisms. The mechanism of drug release depended on the chemical composition of the NFs. RB release from the NFs with highest POX content was caused by the degradation of the nanofiber matrix, whereas the RB release in lower POX content NFs was caused by diffusion. The NFs with POX showed a loss of structural integrity in the presence of hydrogen peroxide as seen using SEM. The MTT assay showed that composite nanofibers had minimal cytotoxicity. We anticipate that nanofibrous PVA/POX can potentially be used to target numerous inflammatory diseases that overproduce hydrogen peroxide and may become a potential candidate for use as a local drug delivery vehicle.     

Cytotoxicity evaluation and antioxidant enzyme expression related to heavy metals found in tuna by-products meal: An in vitro study in human and rat liver cell lines

Heavy metals can accumulate in organisms via various pathways, including respiration, adsorption and ingestion. They are known to generate free radicals and induce oxidative and/or nitrosative stress with depletion of anti-oxidants. Tuna by-product meal (TBM) is rich in proteins and can, therefore, offer an attractive protein source for animals. This study was undertaken to assess the effects of metals present in TBM, namely cadmium (Cd), lead (Pb), and mercury (Hg), separately or in combination with oxidative stress, on cell viability. Three cell models: rat liver FTO2B, human hepatoma HepG2, and human hepatic WRL-68, were used. Cell viability was determined following exposure to various concentrations of the metals. Two antioxidant genes, catalase (CAT) and superoxide dismutase (SOD), were measured to obtain a better understanding of oxidative stress-associated gene expression. Among the metals present in TBM, only Cd at a concentration of 30 μM was noted to exhibit cytotoxic effects. This cytotoxicity was even more pronounced after co-stimulation with H₂O₂, used to mimic systemic oxidative stress. At non-toxic concentrations, Hg and Pb were noted to aggravate oxidative stress toxicity. The results further revealed that exposure to Cd, Pb, and a co-stimulation of H₂O₂ with Hg resulted in the increased expression of antioxidant gene SOD. A risk assessment of toxic contaminants in TBM indicated that food safety objectives should consider the human health impacts of foods derived from animals fed on contaminated meal and that much care should be taken when TBM is used in animal diet.     

Color stability,Roughness, and Microhardness of Enamel and Composites Submitted to Staining/Bleaching Cycles

ObjectiveTo compare the effect of two bleaching systems (bleaching gel and whitening strips) on the color change, roughness, and microhardness of enamel and two resin composites.Material and methodsTwo cavities were prepared on bovine enamel specimens (n = 16) and restored with two composites: a nano-hybrid [Herculite Ultra (HU)] and a micro-hybrid composite [TPH Spectra (TS)]. Baseline color (CIE L*a*b*), roughness (μm), and microhardness (kgf/mm²) were measured using a spectrophotometer, optical profilometer, and Vickers microhardness (VHN) tester, respectively. The specimens were stained with coffee for 14 days, and randomized into two bleaching groups: gel and strips (n = 8), then submitted to a 10-day bleaching/staining test. Color, roughness, and microhardness were re-measured. The outcomes were analyzed using two-way ANOVA and Fisher’s-PLSD test (α = 0.05).ResultsGel significantly improved the color (ΔE 4.9–8.3) and increased the roughness (Ra 0.04–0.08 μm) of all substrates (p < 0.0001) compared to strips. Enamel color was significantly improved (ΔE 5.4–8.3) compared to that of HU (ΔE 2.6–4.9) and TS (ΔE 2.0–4.9) with either gels or strips. TS roughness (0.03–0.08 μm) was significantly higher than that of enamel (0.01–0.05 μm) and HU (0.02–0.04 μm). Enamel had significantly reduced microhardness compared to HU (p = 0.0144).ConclusionGels produced the greatest color improvement and roughness compared to strips. Enamel had significant color improvement but had the greatest decrease in microhardness.Clinical significanceThere was unacceptable color change between enamel and the composites after the combined cyclic effects of staining and bleaching.