Free Radical Theory Research Articles

Effect of particle size and low-temperature secondary oxidation on the active groups in coal structures

To analyze the secondary oxidation of the active structures of pulverized coal and reduce risks of coal spontaneous combustion, free radical theory and functional group analysis were combined to study the effects of particle size and oxidation temperature on the active structure of coal molecules. This process was based on electron paramagnetic resonance (EPR) and Fourier-transform infrared (FTIR) technology. The results show that the reduction in pulverized coal particle size can enhance the secondary oxidation activity of coal and that the reactivity is the strongest when the particle size is 0.074−0 mm. The smaller the coal particle size is, the shorter the aliphatic side chain is after secondary oxidation. The reaction in which the side chain breaks to form a stable chain structure is also more intense. A smaller coal particle size also makes it easier to produce −OH after secondary oxidation, resulting in a large increase in the Average A (−OH) in the Coal 1# and Coal 3# at the minimum particle size range of 0.074−0 mm. The −C=O and −C−O− in Coal 1# with a lower metamorphic grade are greatly affected by temperature and particle size, and the consumption of −C=O during oxidation plays a dominant role in the secondary oxidation process. The −C=O and −C−O− in Coal 2# and Coal 3# are less affected by temperature and more affected by particle size, and −C−O− is the main group driving the secondary oxidation reaction.

A Review of the Catalytic Effects of Lead‐Based Ballistic Modifiers on the Combustion Chemistry of Double Base Propellants

AbstractLead‐based compounds are the current industry‐standard ballistic modifier for double‐base propellants, but there is a pressing need for alternatives as incoming European legislation will soon ban their use. This review article introduces the main concepts and terminologies in the combustion chemistry of double‐base propellants, and critically evaluates the four theories put forward in the literature to account for the ballistic modifier effect, namely (i) photochemical, (ii) chelating/complex, (iii) carbon soot, and (iv) free radical theories. We also review the literature on current trends in ballistic modifier research and note the emerging potential of oxide nanoparticles (in particular Bi2WO6) and Cu/Bi encapsulated in carbon nanotubes as lead‐free ballistic modifier additives.

Mitochondrial transformations in the aging human placenta.

Mitochondria play a key role in homeostasis and are central to one of the leading hypotheses of aging, the free radical theory. Mitochondria function as a reticulated network, constantly adapting to the cellular environment through fusion (joining), biogenesis (formation of new mitochondria), and fission (separation). This adaptive response is particularly important in response to oxidative stress, cellular damage, and aging, when mitochondria are selectively removed through mitophagy, a mitochondrial equivalent of autophagy. During this complex process, mitochondria influence surrounding cell biology and organelles through the release of signaling molecules. Given that the human placenta is a unique organ having a transient and somewhat defined life span of ∼280 days, any adaption or dysfunction associated with mitochondrial physiology as a result of aging will have a dramatic impact on the health and function of both the placenta and the fetus. Additionally, a defective placenta during gestation, resulting in reduced fetal growth, has been shown to influence the development of chronic disease in later life. In this review we focus on the mitochondrial adaptions and transformations that accompany gestational length and share similarities with age-related diseases. In addition, we discuss the role of such changes in regulating placental function throughout gestation, the etiology of gestational complications, and the development of chronic diseases later in life.

Updating the Free Radical Theory of Aging

Updating the Free Radical Theory of Aging

Mitochondria: Aging, Metabolic Syndrome and Cardiovascular Diseases. Formation of a New Paradigm

Cardiovascular diseases are among the major causes of mortality among aged people in most developed countries. Oxidative stress, which causes mutations of mitochondrial DNA and mitochondrial dysfunctions, was considered as the main mechanism of heart failure and other pathologies of old age. However, in recent years the prior paradigm of mechanisms of aging, oxidative stress and antioxidative defense was questioned and in some aspects even turned out to be wrong. In this review, we discuss the new data that led to the need to reconsider paradigms. We show that although the mitochondrial free radical theory of aging remains valid, the radical responsible for the aging is the protonated form of the superoxide radical, namely perhydroxyl radical, which was largely ignored all previous years. Perhydroxyl radical initiates the isoprostane pathway of lipid peroxidation (IPLP) of polyunsaturated fatty acids, which are part of the phospholipid core of the mitochondrial inner membrane. IPLP was discovered 30 years ago by Roberts and Morrow at the Vanderbilt University, but the mechanism of its initiation remained unknown. The IPLP causes formation of the racemic mixture of hundreds of biologically active products, named isoprostanes, and highly toxic molecules, first of all isolevuglandins. We distinguish two types of damages caused by IPLP during aging. The first one is associated with oxidative damages to cardiolipin and phosphatidylethanolamine (PEA), which result in disruption of polyenzymatic complexes of the oxidative phosphorylation system. The second type of dysfunctions is caused by the direct actions of toxic products on the lysine-containing proteins and PEA. To this type of mitochondrial damages evidently belongs the oxidative damage of the mitochondrial DNA polymerase, which results in a 20-fold increase in mutations of mitochondrial mtDNA.

Effect of Nitrogen Reactive Compounds on Aging in Seed.

Reactive nitrogen species (RNS) are universal compounds that are constantly present in plant cells. RNS function depends on their actual level (the “nitrosative door” concept), duration of plant exposure to RNS and the context of the exposure. RNS are involved in the nitration of nucleic acids and fatty acids, posttranslational protein modifications (nitration and S-nitrosylation), and modulation of reactive oxygen species metabolism. RNS are regulatory molecules of various physiological processes in plants, including seed formation, maturation, dormancy and germination. The free radical theory of aging, well documented for animals, indicated that RNS participate in the regulation of the life span. Some data point to RNS contribution in preservation of seed vigor and/or regulation of seed longevity. Seed aging is a problem for biologists and agriculture, which could be solved by application of RNS, as a factor that may potentially expand seed vitality resulting in increased germination rate. The review is focused on RNS, particularly nitric oxide contribution to regulation of seed aging.

The Effect of Giving Dadih on Malondialdehyde Levels and Renal Interstitial Fibrosis at Aging Kidney

BACKGROUND: The increase in the elderly poses problems in the areas of health, since it can cause aging of the physiological function of organs. It also has an impact on kidney function, which will enhance the chronic kidney disease. One of the theory that causes aging process is the free radical theory, which that accumulation of free radicals is caused by depletion of antioxidants. Therefore, exogenous antioxidants are needed and in this study author use dadih. Dadih is fermented buffalo milk, indigenous from West Sumatera-Indonesia. Peptides found in fermented milk contained antioxidant that can stimulate the formation of endogenous antioxidants and diversification of dadiah increases its effect as antioxidant.
 AIM: This study aims to prove the effect of dadih antioxidants on malondialdehyde (MDA) levels of kidney tissue and renal interstitial fibrosis.
 MATERIALS AND METHODS: An experimental study with post-test only control group design conducted to observe effect of dadih to kidney aging of Rattus norvegicus in the Laboratory of Andalas University. It used 30 R. norvegicus which were divided into three groups. Group K was a positive control (did not get dadih), Group P1 was given dadih 4.5 g once a day, and Group P2 was given dadih 4.5 g twice a day for 42 days. After that, MDA levels of kidney tissue are examined using the thiobarbituric acid reactive substances examination technique and examination of renal interstitial fibrosis which is done by histopathology with Sirius-red staining. Data were analyzed using the normality test with Shapiro–Wilk.
 RESULTS: The results showed that dadih can reduce levels of MDA in kidney tissue, where its decrease very significant in Group P1 (given dadih once a day) and Group P2 (given dadih twice a day) compared to the Group K (control group) 0.97 ± 0.06 pg/ml to 0.75 ± 0.03 pg/ml (p < 0.05). Group P1 and Group P2 can also reduce the renal interstitial fibrosis rank. Obtained a decrease in the average fibrosis rank from Group K to Group P1 and subsequently to Group P2 (p < 0.05).
 CONCLUSION: This study concluded that dadih can reduce MDA levels in kidney tissue and reduce renal interstitial fibrosis rank on aging kidney.

ОКИСЛИТЕЛЬНЫЙ СТРЕСС ПРИ СТАРЕНИИ

Выдвинутая более 50 лет назад Д. Харманом свободнорадикальная теория старения остается популярной и сегодня. В обзоре проведен анализ возрастных изменений основных эндогенных механизмов продукции активированных кислородных метаболитов (АКМ) и механизмов антиоксидантной защиты. С возрастом генерация АКМ митохондриями, пероксисомами и NAD(P) H -оксидазами усиливается, в то время как транскрипционная активность важной системы поддержания редокс-баланса Keap 1/ Nrf 2/ ARE уменьшается. У старых животных отмечается также низкая активность аутофагии, удаляющей из клеток поврежденные органеллы и агрегированные структуры. Возрастное смещение редокс-баланса в сторону окислительного стресса может являться причиной развития возраст-ассоциированных нейрогеденеративных, аутоиммунных и воспалительных патологий. The free-radical theory of aging, advanced more than 50 years ago by D. Harman, remains popular today. The review analyzes age-related changes in the main endogenous mechanisms of reactive oxygen species (ROS) production and antioxidant defense mechanisms. With age, ROS generation by mitochondria, peroxisomes, and NAD(P)H oxidases is enhanced, while the transcriptional activity of the important system Keap 1/ Nrf 2/ ARE maintaining redox balance decreases. In old animals, autophagy activity is also low, which removes damaged organelles and aggregated structures from cells. The age-related shift of the redox balance towards oxidative stress can cause the development of age-associated neurodegenerative, autoimmune and infl ammatory pathologies.

Mitophagy in Hypertension-Associated Premature Vascular Aging.

Hypertension has been described as a condition of premature vascular aging, relative to actual chronological age. In fact, many factors that contribute to the deterioration of vascular function as we age are accelerated and exacerbated in hypertension. Nonetheless, the precise mechanisms that underlie the aged phenotype of arteries from hypertensive patients and animals remain elusive. Classically, the aged phenotype is the buildup of cellular debris and dysfunctional organelles. One means by which this can occur is insufficient degradation and cellular recycling. Mitophagy is the selective catabolism of damaged mitochondria. Mitochondria are organelles that contribute importantly to the determination of cellular age via their production of reactive oxygen species (ROS; Harman’s free radical theory of aging). Therefore, the accumulation of dysfunctional and ROS-producing mitochondria could contribute to the acceleration of vascular age in hypertension. This review will address and critically evaluate the current literature on mitophagy in vascular physiology and hypertension.

Recent Review on Oxidative stress, Cellular senescence and Age-Associated Diseases

Reactive Oxygen Species (ROS) is considered as the main factor of the Free Radical theory of aging over centuries and it indicates the pathophysiology of aging in mammals. ROS causes oxidative stress, which is a major component in the aging process of higher organisms. ROS also leads to many age-related diseases such as cancer, cardiovascular disease, diabetes, etc. ROS causes damage to most of the biological membranes that cause these chronic diseases. Enhanced ROS levels at the cellular level lead to cellular senescence. It is a stage of cells where growth arrest happens associated with the secretion of Senescence-associated secretory phenotype (SASP) factors. Senescence maintains tissue homeostasis, functions in normal development and restricts tumor development. In this regard, recent experimental evidence has shown that the genetic or pharmacological ablation of senescent cells extends the life span and improves the healthspan. Here, we review the cellular and molecular links between cellular senescence and aging and discuss the novel therapeutic avenues that this connection opens.

Exploring the role of host specialisation and oxidative stress in interspecific lifespan variation in subtropical tephritid flies

In herbivorous insects, the degree of host specialisation may be one ecological factor that shapes lifespan. Because host specialists can only exploit a limited number of plants, their lifecycle should be synchronised with host phenology to allow reproduction when suitable hosts are available. For species not undergoing diapause or dormancy, one strategy to achieve this could be evolving long lifespans. From a physiological perspective, oxidative stress could explain how lifespan is related to degree of host specialisation. Oxidative stress caused by Reactive Oxygen Species (ROS) might help underpin ageing (the Free Radical Theory of Aging (FRTA)) and mediate differences in lifespan. Here, we investigated how lifespan is shaped by the degree of host specialisation, phylogeny, oxidative damage accumulation and antioxidant protection in eight species of true fruit flies (Diptera: Tephritidae). We found that lifespan was not constrained by species relatedness or oxidative damage (arguing against the FRTA); nevertheless, average lifespan was positively associated with antioxidant protection. There was no lifespan difference between generalist and specialist species, but most of the tephritids studied had long lifespans in comparison with other dipterans. Long lifespan may be a trait under selection in fruit-feeding insects that do not use diapause.

NoxO1 Knockout Promotes Longevity in Mice.

According to the free radical theory of aging, reactive oxygen species (ROS) have been proposed to be a major cause of aging for a long time. Meanwhile, it became clear that ROS have diverse functions in a healthy organism. They act as second messengers, and as transient inhibitors of phosphatases and others. In fact, their detrimental role is highly dependent on the context of their production. NADPH oxidases (Nox) have been discovered as a controllable source of ROS. NoxO1 enables constitutive ROS formation by Nox1 by acting as a constitutively active cytosolic subunit of the complex. We previously found that both Nox1 and NoxO1 were highly expressed in the colon, and that NoxO1-/- deficiency reduces colon health. We hypothesized that a healthy colon potentially contributes to longevity and NoxO1 deficiency would reduce lifetime, at least in mouse. In contrast, here we provide evidence that the knockout of NoxO1 results in an elongated life expectancy of mice. No better endothelial function, nor an improved expression of genes related to longevity, such as Sirt1, were found, and therefore may not serve as an explanation for a longer life in NoxO1 deficiency. Rather minor systemic differences, such as lower body weight occur. As a potential reason for longer life, we suggest better DNA repair capacity in NoxO1 deficient mice. Although final fatal DNA damage appears similar between wildtype and NoxO1 knockout animals, we identified less intermediate DNA damage in colon cells of NoxO1-/- mice, while the number of cells with intact DNA is elevated in NoxO1-/- colons. We conclude that NoxO1 deficiency prolongs lifetime of mice, which correlates with less intermediate and potentially fixable DNA damage at least in colon cells.

Pathogenesis of Photoaging in Human Dermal Fibroblasts

Pathogenesis of Photoaging in Human Dermal Fibroblasts

HORMESE, ENVELHECIMENTO E TOXICIDADE: ESTADO DA ARTE

O envelhecimento é um processo natural e progressivo, o qual acomete aspectos do individuo de forma holística. Um organismo envelhecido, em condições normais, poderá sobreviver adequadamente, porém, quando submetido a situações de stress toxicológico, físico, emocional, entre outros, pode apresentar dificuldades em manter a sua homeostase e levando o mesmo a desencadear o mecanismo de hormese. A Hormese deriva do grego “hormaein” que significa “excitar”. Em sua primeira definição foi descrita como um comportamento bifásico, ou seja, uma habilidade biológica que pode ser modificada por baixas doses de um xenobiótico, mas inibida por doses elevadas do mesmo, ela foi proposta como uma explicação para alterações na homeostase. Uma das teorias mais bem aceitas relacionadas ao envelhecimento é a teoria dos radicais livres. Além dos radicais livres outros xenobióticos podem estar intrinsecamente correlacionados a senescência de células nervosas, como drogas de abuso, medicamentos de uso continuo, toxinas e fármacos, entre outros. Este artigo vislumbra apresentar de forma cientifica uma revisão bibliográfica sistemática, trazendo os temas hormese, envelhecimento e toxicologia correlacionados as áreas da saúde, toxicologia e regulação, mostrando o equivoco de fundamental na natureza quando são avaliadas respostas apenas observando a tríade dose x resposta x exposição. Durante as primeiras décadas do século XX este erro foi o resultado de múltiplos fatores, incluindo o conflito entre homeopatia e medicina tradicional, além disso, as avaliações das respostas da dose hormética são de difícil interpretação, exigindo mais atenção e abstração quanto comparado aos modelos lineares, tradicionalmente aceitos pela maioria da comunidade cientifica. O conceito hormese ajuda os pesquisadores a abordar melhor forma de respostas a baixa dose, mostrando que existe capacidade de adaptação dos organismos e podendo abrir um novo olhar sobre o início doenças degenerativas crônicas e gerando quebra de paradigmas no que tange essa ótica.
 Palavras chave: Envelhecimento. Hormese. Toxicidade. 

The Exacerbation of Aging and Oxidative Stress in the Epididymis of Sod1 Null Mice

There is growing evidence that the quality of spermatozoa decreases with age and that children of older fathers have a higher incidence of birth defects and genetic mutations. The free radical theory of aging proposes that changes with aging are due to the accumulation of damage induced by exposure to excess reactive oxygen species. We showed previously that absence of the superoxide dismutase 1 (Sod1) antioxidant gene results in impaired mechanisms of repairing DNA damage in the testis in young Sod1−/− mice. In this study, we examined the effects of aging and the Sod−/− mutation on mice epididymal histology and the expression of markers of oxidative damage. We found that both oxidative nucleic acid damage (via 8-hydroxyguanosine) and lipid peroxidation (via 4-hydroxynonenal) increased with age and in Sod1−/− mice. These findings indicate that lack of SOD1 results in an exacerbation of the oxidative damage accumulation-related aging phenotype.

Organismal Aging and Oxidants beyond Macromolecules Damage.

The relationship between oxidants and organismal aging was first articulated through the free radical theory of aging. One of the major predictions of the free radical theory of aging is that oxidative stress shortens organisms' lifespan because of an increased level of oxidants, which are damaging to macromolecules. However, challenging the role of oxidants in age-related diseases, there is now sufficient evidence that antioxidant supplements do not provide significant health benefits. Interestingly, in addition to an increase in oxidant-mediated macromolecules damage, there is convincing experimental data to support the role of senescent cells in the process of aging. Here, the current knowledge regarding the role of oxidants and cellular senescence in organismal aging is reviewed and it is proposed that, in addition to the role of oxidants as inducers of macromolecular damage, oxidants may also function as regulators of signaling pathways involved in the establishment of cellular senescence. If this role for oxidants is established, it may be necessary to modify the free radical theory of aging from "Organisms age because cells accumulate reactive oxygen species-dependent damage over time" to: "Organisms age because cells accumulate oxidants'-dependent damage and oxidants'-dependent senescent characteristics over time."

Mitochondrial base excision repair positively correlates with longevity in the liver and heart of mammals.

Damage to DNA is especially important for aging. High DNA repair could contribute, in principle, to lower such damage in long-lived species. However, previous studies showed that repair of endogenous damage to nuclear DNA (base excision repair, BER) is negatively or not correlated with mammalian longevity. However, we hypothesize here that mitochondrial, instead of nuclear, BER is higher in long-lived than in short-lived mammals. We have thus measured activities and/or protein levels of various BER enzymes including DNA glycosylases, NTHL1 and NEIL2, and the APE endonuclease both in total and mitochondrial liver and heart fractions from up to eight mammalian species differing by 13-fold in longevity. Our results show, for the first time, a positive correlation between (mitochondrial) BER and mammalian longevity. This suggests that the low steady-state oxidative damage in mitochondrial DNA of long-lived species would be due to both their lower mitochondrial ROS generation and their higher mitochondrial BER. Long-lived mammals do not need to continuously maintain high nuclear BER levels because they release less mitROS to the cytosol. This can be the reason why they tend to show lower nuclear BER values. The higher mitochondrial BER of long-lived mammals contributes to their superior longevity, agrees with the updated version of the mitochondrial free radical theory of aging, and indicates the special relevance of mitochondria and mitROS for aging.

Healthy Aging: Antioxidants, Uncouplers and/or Telomerase?

The free radical theory of aging was proposed in 1956. Although it does not fully describe the mechanisms of aging, it is generally accepted that reactive oxygen species (ROS) are one of the pathogenetic factors in aging and, in particular, in the development of pathologies associated with aging. The main source of ROS in the cell is mitochondria. Antioxidants directed to mitochondria have a positive effect, but have low efficiency. The problem is that increased amounts of antioxidants disrupt normal cellular redox reactions, and a low amount of antioxidants is not able to seriously affect the processes. Protection against ROS may be more effective if the rate of ROS formation is reduced. There is a natural mitochondrial uncoupling process that significantly reduces ROS production. The weak uncoupler dinitrophenol (DNP) prolongs the life span of mice, reduces traumatic brain damage, and inhibits the development of a number of neurodegenerative diseases. Unfortunately, DNP has a number of disadvantages that hinder its practical use. Uncoupling of oxidative phosphorylation by free fatty acids is a natural mechanism, the activation of which can be used in medicine. The third (after antioxidants and uncouplers), but so far little studied, method of reducing ROS is telomerase, which, under conditions of oxidative stress, is transported into the mitochondria and improves cell survival by reducing ROS production.

The theory of free radicals and aging: A review article

The theory of free radicals and aging: A review article

До питання про теоретичні основи соціальної роботи з військовослужбовцями (на основі світових і вітчизняних теорій)

The article for the first time reveals the theoretical foundations of modern social work with servicemen in Ukraine on the basis of analysis of theories of social work, taking into account the peculiarities of military service as a profession, the purpose of social work in the army. The methodology chose an epistemological approach to the study. And the methods for research were: theoretical analysis of sources, concretization, generalization, systematization. The article analyzes the advantages and disadvantages of comprehensively oriented, psychologically oriented and sociologically oriented theories of social work. The authors on the basis of theoretical analysis of sources, features of military service formulated a list of theories that should be used in the implementation of social work with servicemen. For these theories identified their advantages, capabilities, limits and problem area of application. the theory of help for self-help and the theory of education for social work with servicemen are analyzed. It is shown that there is no universal theory for such social work, their complex is expedient for application in practice of rendering of social services. It is proved that feminist and free-radical theories are not suitable for work with military.