Siroheme‐containing sulfite reductase: A density functional investigation of the mechanism

Siroheme‐containing sulfite reductases (SiR) catalyze the six‐electron reduction of sulfite to sulfide via a mechanism involving sulfite binding at the heme iron. The exact sequence in which the required electrons and protons are delivered to the heme‐bound sulfite has received little attention to date. Here, a detailed account is given of these steps, based on density functional theory, thus providing data for the first attempt to draw a detailed picture of sulfite reduction in SiR by theoretical methods. Parallels are shown with reduction of other small molecules at heme centers: dioxygen (including generation of sulfide high‐valent iron centers akin to hemoproteins Compounds I and II), nitrite (including linkage isomerism akin to the nitro/nitrito known for nitrite reducing proteins), or nitric oxide. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

Potential role of HMG CoA reductase inhibitor on oxidative stress induced by advanced glycation endproducts in vascular smooth muscle cells of diabetic vasculopathy

Advanced glycation endproducts (AGEs)-induced vascular smooth muscle cell (VSMCs) proliferation and formation of reactive oxygen species (ROS) are emerging as one of the important mechanisms of diabetic vasculopathy but little is known about the antioxidative action of HMG CoA reductase inhibitor (statin) on AGEs. We hypothesized that statin might reduce AGEs-induced intracellular ROS of VSMCs and analyzed the possible mechanism of action of statin in AGEs-induced cellular signaling. Aortic smooth muscle cell of Sprague-Dawley rat (RASMC) culture was done using the different levels of AGEs stimulation in the presence or absence of statin. The proliferation of RASMC, ROS formation and cellular signaling was evaluated and neointimal formation after balloon injury in diabetic rats was analyzed. Increasing concentration of AGEs stimulation was associated with increased RASMC proliferation and increased ROS formation and they were decreased with statin in a dose-dependent manner. Increased NF-κB p65, phosphorylated ERK, phosphorylated p38 MAPK, cyclooxygenase-2, and c-jun by AGEs stimulation were noted and their expression was inhibited by statin. Neointimal formation after balloon injury was much thicker in diabetic rats than the sham-treated group but less neointimal growth was observed in those treated with statin after balloon injury. Increased ROS formation, subsequent activation of MAPK system and increased VSMC proliferation may be possible mechanisms of diabetic vasculopathy induced by AGEs and statin may play a key role in the treatment of AGEs-induced diabetic atherosclerosis.     

Nephroprotective Effects of Alhagi camelorum against Cisplatin-Induced Nephrotoxicity in Albino Wistar Rats

Alhagi camelorum (AC) is an old plant with a significant therapeutic value throughout Africa, Asia, and Latin America. The overuse of cisplatin (Cis > 50 mg/m²) is associated with observed nephrotoxicity, ototoxicity, gastrotoxicity, myelosuppression, and allergic reactions. Remedial measures are needed for the protection of nephrotoxicity against cisplatin. Thus, we investigated the nephroprotective effects of AC plant extract to prevent cisplatin-induced nephrotoxicity in albino Wistar rats. The presence of polyphenols, phenolic compounds, tannins, and saponins was revealed during phytochemical investigation, and a significantly intense antioxidant activity was recorded. There were no toxicological symptoms in the treated rats, and no anatomical, physiological, or histological abnormalities were found compared to the control rats. The results of correcting cisplatin-induced nephrotoxicity revealed that the extract has a significant ability to treat kidney damage, with most parameters returning to normal after only three weeks of therapy. It is concluded that co-administration of cisplatin with AC extract showed exceptional nephroprotective effects at a dose of 600 mg/kg for Cis-induced nephrotoxicity.     

Continuous hypoxia attenuates paraquat-induced cytotoxicity in the human A549 lung carcinoma cell line

Paraquat (1,1'-dimethyl-4,4'-bipyridinium dichloride; PQ), an effective and widely used herbicide, was commercially introduced in 1962. It is reduced by the electron donor NADPH, and then reduced PQ transfers the electrons to molecular oxygen, resulting in the production of reactive oxygen species (ROS), which are related to cellular toxicity. However, the influence of continuous hypoxia on PQ-induced ROS production has not fully been investigated. We evaluated in vitro the protective effect of continuous hypoxia on PQ-induced cytotoxicity in the human carcinogenic alveolar basal epithelial cell line (A549 cells) by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and live and dead assay, and by measuring lactate dehydrogenase (LDH) release. To elucidate the mechanism underlying this effect, we monitored the immunofluorescence of intracellular ROS and measured malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. Continuous hypoxia protected the A549 cells from PQ-induced cytotoxicity. Continuous hypoxia for a period of 24 h significantly reduced intracellular ROS, decreased MDA concentration in the supernatant, and normalized SOD and GPx activities. Continuous hypoxia attenuated PQ-induced cell toxicity in A549 cells. This protective effect might be attributable to the suppression of PQ-induced ROS generation.     

Antioxidant Activity and Anti-Apoptotic Effect of the Small Molecule Procyanidin B1 in Early Mouse Embryonic Development Produced by Somatic Cell Nuclear Transfer

As an antioxidant, procyanidin B1(PB1) can improve the development of somatic cell nuclear transfer (SCNT) embryos; PB1 reduces the level of oxidative stress (OS) during the in vitro development of SCNT embryos by decreasing the level of reactive oxygen species (ROS) and increasing the level of glutathione (GSH) and mitochondrial membrane potential (MMP). Metabolite hydrogen peroxide (H₂O₂) produces OS. Catalase (CAT) can degrade hydrogen peroxide so that it produces less toxic water (H₂O) and oxygen (O₂) in order to reduce the harm caused by H₂O₂. Therefore, we tested the CAT level in the in vitro development of SCNT embryos; it was found that PB1 can increase the expression of CAT, indicating that PB1 can offset the harm caused by oxidative stress by increasing the level of CAT. Moreover, if H₂O₂ accumulates excessively, it produces radical-(HO-) through Fe^2+/3+ and damage to DNA. The damage caused to the DNA is mainly repaired by the protein encoded by the DNA damage repair gene. Therefore, we tested the expression of the DNA damage repair gene, OGG1. It was found that PB1 can increase the expression of OGG1 and increase the expression of protein. Through the above test, we proved that PB1 can improve the repairability of DNA damage. DNA damage can lead to cell apoptosis; therefore, we also tested the level of apoptosis of blastocysts, and we found that PB1 reduced the level of apoptosis. In summary, our results show that PB1 reduces the accumulation of H₂O₂ by decreasing the level of OS during the in vitro development of SCNT embryos and improves the repairability of DNA damage to reduce cell apoptosis. Our results have important significance for the improvement of the development of SCNT embryos in vitro and provide important reference significance for diseases that can be treated using SCNT technology.     

Chemiluminescence and Bioluminescence as an Excitation Source in the Photodynamic Therapy of Cancer: A Critical Review

Photodynamic therapy (PDT) of cancer is known for its limited number of side effects, and requires light, oxygen and photosensitizer. However, PDT is limited by poor penetration of light into deeply localized tissues, and the use of external light sources is required. Thus, researchers have been studying ways to improve the effectiveness of this phototherapy and expand it for the treatment of the deepest cancers, by using chemiluminescent or bioluminescent formulations to excite the photosensitizer by intracellular generation of light. The aim of this Minireview is to give a précis of the most important general chemi‐/bioluminescence mechanisms and to analyze several studies that apply them for PDT. These studies have demonstrated the potential of utilizing chemi‐/bioluminescence as excitation source in the PDT of cancer, besides combining new approaches to overcome the limitations of this mode of treatment.     

A novel Ag/Ag3PO4-IRMOF-1 nanocomposite for antibacterial application in the dark and under visible light irradiation

MOF-5 that sometimes called IRMOF-1 has been intensively studied in recent years to develop efficient photocatalyst to degrade refractory organics and inactivate bacteria for wastewater treatment. In the present work, Ag/Ag₃PO₄ nanoparticles incorporated in IRMOF-1 was successfully prepared via hydrothermal approach. The antibacterial activity of synthesized materials (IRMOF-1, Ag/Ag₃PO₄ nanoparticles and Ag/Ag₃PO₄-IRMOF-1 nanocomposite was compared against two types of bacteria (Escherichia coli (E. coil) as Gram negative and Staphylococcus aureus (S. aureus) as Gram-positive bacteria). The deactivation of the bacteria by the prepared material was measured in the dark and under visible light irradiation. The antibacterial activity of synthesized samples was investigated by determining the minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), growth inhibition assay and inhibition zone. The Ag/Ag₃PO₄-IRMOF-1 nanocomposite exhibited stronger antibacterial activities than the Ag/Ag₃PO₄ nanoparticles and IRMOF-1 at all tested bacteria types. Based on inhibition zone, without any light irradiation, Ag/Ag₃PO₄-IRMOF-1 nanocomposite showed activity toward E. coil, but in presence of light nanocomposite depicted activity toward S. aureus. The results demonstrated that antibacterial activity of all synthesized samples in the dark and light against S. aureus bacteria was more than E. coil bacteria. The antibacterial activity mechanism was due to sustained-release of silver ions in the dark and reactive oxygen species (ROS) under visible light. The bioactivity of IRMOF-1 was related to the degradation of the its structure and the release of Zn²⁺ ions into the culture medium that bind to the cell wall and deactivation bacteria.     

纳米氧化铈的抗氧化生物应用

CeO2是一种常见的催化材料,具有很高的实用及研究价值．人们在其形貌的可控合成以及催化活性的调节等方面进行了大量的研究,取得了很多成果．近年来,随着纳米材料生物应用研究的兴起,纳米氧化铈在生物抗氧化领域的应用受到了越来越多的关注．在纳米尺度下,由于表面氧缺陷的产生,氧化铈中部分cd4＋被还原为Ce3＋以稳定缺陷．此时材料中的Ce3＋和Ce^4＋能够可逆的转化,这一性质使得纳米CeO2能够催化分解生物体内的过量自由基,从而为治疗氧化应激类疾病提供了一种可能．本综述对纳米CeO2的生物抗氧化作用进行了总结,重点讨论了CeO2纳米颗粒的抗氧化机理以及影响其生物效应的关键因素,还介绍了纳米CeO2生物安全性相关的一些研究,并对其生物应用前景进行了展望．     

Cytoprotective Activity of p-Terphenyl Polyketides and Flavuside B from Marine-Derived Fungi against Oxidative Stress in Neuro-2a Cells

The influence of p-terphenyl polyketides 1–3 from Aspergillus candidus KMM 4676 and cerebroside flavuside B (4) from Penicillium islandicum (=Talaromyces islandicus) against the effect of neurotoxins, rotenone and paraquat, on Neuro-2a cell viability by MTT and LDH release assays and intracellular ROS level, as well as DPPH radical scavenging activity, was investigated. Pre-incubation with compounds significantly diminished the ROS level in rotenone- and paraquat-treated cells. It was shown that the investigated polyketides 1–3 significantly increased the viability of rotenone- and paraquat-treated cells in two of the used assays but they affected only the viability of paraquat-treated cells in the LDH release assay. Flavuside B statistically increased the viability of paraquat-treated cells in both MTT and LDH release assays, however, it increased the viability of rotenone-treated cells in the LDH release assay. Structure–activity relationships for p-terphenyl derivatives, as well as possible mechanisms of cytoprotective action of all studied compounds, were discussed.     

High Hydrostatic Pressure to Increase the Biosynthesis and Extraction of Phenolic Compounds in Food: A Review

Phenolic compounds from fruits and vegetables have shown antioxidant, anticancer, anti-inflammatory, among other beneficial properties for human health. All these benefits have motivated multiple studies about preserving, extracting, and even increasing the concentration of these compounds in foods. A diverse group of vegetable products treated with High Hydrostatic Pressure (HHP) at different pressure and time have shown higher phenolic content than their untreated counterparts. The increments have been associated with an improvement in their extraction from cellular tissues and even with the activation of the biosynthetic pathway for their production. The application of HHP from 500 to 600 MPa, has been shown to cause cell wall disruption facilitating the release of phenolic compounds from cell compartments. HPP treatments ranging from 15 to 100 MPa during 10–20 min at room temperature have produced changes in phenolic biosynthesis with increments up to 155%. This review analyzes the use of HHP as a method to increase the phenolic content in vegetable systems. Phenolic content changes are associated with either an immediate stress response, with a consequent improvement in their extraction from cellular tissues, or a late stress response that activates the biosynthetic pathways of phenolics in plants.     

Imaging of Hypochlorous Acid by Fluorescence and Applications in Biological Systems

In recent decades, HOCl research has attracted a lot of scientists from around the world. This chemical species is well known as an important player in the biological systems of eukaryotic organisms including humans. In the human body, HOCl is produced by the myeloperoxidase enzyme from superoxide in very low concentrations (20 to 400 μm ); this species is secreted by neutrophils and monocytes to help fight pathogens. However, in the condition called “oxidative stress”, HOCl has the capability to attack many important biomolecules such as amino acids, proteins, nucleotides, nucleic acids, carbohydrates, and lipids; these reactions could ultimately contribute to a number of diseases such as neurodegenerative diseases (AD, PD, and ALS), cardiovascular diseases, and diabetes. In this review, we discuss recent efforts by scientists to synthesize various fluorophores which are attached to receptors to detect HOCl such as: chalcogen‐based oxidation, oxidation of 4‐methoxyphenol, oxime/imine, lactone ring opening, and hydrazine. These synthetic molecules, involving rational synthetic pathways, allow us to chemoselectively target HOCl and to study the level of HOCl selectivity through emission responses. Virtually all the reports here deal with well‐defined and small synthetic molecular systems. A large number of published compounds have been reported over the past years; this growing field has given scientists new insights regarding the design of the chemosensors. Reversibility, for example is considered important from the stand point of chemosensor reuse within the biological system; facile regenerability using secondary analytes to obtain the initial probe is a very promising avenue. Another aspect which is also important is the energy of the emission wavelength of the sensor; near‐infrared (NIR) emission is favorable to prevent autofluorescence and harmful irradiation of tissue; thus, extended applicability of such sensors can be made to the mouse model or animal model to help image internal organs. In this review, we describe several well‐known types of receptors that are covalently attached to the fluorophore to detect HOCl. We also discuss the common fluorophores which are used by chemist to detect HOCl, Apart from the chemical aspects, we also discuss the capabilities of the compounds to detect HOCl in living cells as measured through confocal imaging. The growing insight from HOCl probing suggests that there is still much room for improvement regarding the available molecular designs, knowledge of interplay between analytes, biological applicability, biological targeting, and chemical switching, which can also serve to further sensor and theurapeutic agent development alike.     

Simultaneous analysis of multiple urinary biomarkers for the evaluation of oxidative stress by automated online in‐tube solid‐phase microextraction coupled with negative/positive ion‐switching mode liquid chromatography–tandem mass spectrometry

This study described an automated online method for the simultaneous determination of 8‐isoprostane, 8‐hydroxy‐2′‐deoxyguanosine, and 3‐nitro‐l ‐tyrosine in human urine. The method involves in‐tube solid‐phase microextraction using a Carboxen 1006 PLOT capillary column as an extraction device, followed by liquid chromatography with tandem mass spectrometry using a CX column and detection in the negative/positive switching ion‐mode by multiple reaction monitoring. Using their stable isotope‐labeled internal standards, each of these oxidative stress biomarkers showed good linearity from 0.02 to 2.0 ng/mL. Their detection limits (S/N = 3) were 3.4–21.5 pg/mL, and their intra‐ and inter‐day precisions (relative standard deviations) were >3.9 and 6.5% (n = 5), respectively. This method was applied successfully to the analysis of urine samples, without any other pretreatment and interference peaks.     

A Concise Review of Current In Vitro Chemical and Cell-Based Antioxidant Assay Methods

Antioxidants remain interesting molecules of choice for suppression of the toxic effects of free radicals in foods and human systems. The current practice involves the use of mainly synthetic molecules as potent antioxidant agents. However, due to the potential negative impact on human health, there is an intensive effort within the research community to develop natural alternatives with similar antioxidant efficacy but without the negative side effects of synthetic molecules. Still, the successful development of new molecules depends on the use of reliable chemical or cell culture assays to screen antioxidant properties. Chemical antioxidant assays include the determination of scavenging ability against free radicals such as DPPH, superoxide anion radicals, hydroxyl radicals, hydrogen peroxide, and nitric oxide. Other antioxidant tests include the ability of compounds to bind and sequester prooxidant metal cations, reduce ferric iron, and attenuate the rate of lipid oxidation. Ex vivo tests utilize cell cultures to confirm entry of the molecules into cells and the ability to quench synthetic intracellular free radicals or to stimulate the increased biosynthesis of endogenous antioxidants. In order to assist researchers in their choice of antioxidant evaluation methods, this review presents background scientific information on some of the most commonly used antioxidant assays with a comparative discussion of the relevance of published literature data to food science and human nutrition applications.     

Mitochondria-Targeting Plasmonic Spiky Nanorods Increase the Elimination of Aging Cells in Vivo

Cellular senescence is stress-induced, irreversible growth arrest, and is thought to impair tissue function. The clearance of senescent cells can delay the features of senescence. Herein, we report the development of plasmonic core–shell spiky nanorods (CSNRs) surface-modified with an anti-beta-2-microglobulin (aB2MG) antibody and triphenylphosphonium (TPP), to target the mitochondria in senescent cells. aB2MG-TPP@CSNRs irradiated with near-infrared (NIR) light selectively caused mitochondrial damage and apoptosis of senescent cells with relatively low NIR light power, and the ability of CSNRs to activate and amplify the immune response in vitro and in vivo was discovered. The photo-induced generation of reactive oxygen species (ROS) resulted in senescent-cell apoptosis and immune adjuvant effect by CSNRs accelerated the clearance of senescent cells in mice. This study opens the way for the use of precisely regulated plasmonic nanostructures for immune adjuvant and photo-induced apoptosis for age-related senescence.