Toxic Effects Of Oxygen Research Articles

Toxic effects of oxygen and how to deal with them in a critical condition. A view from the standpoint of pathophysiology

Toxic effects of oxygen and how to deal with them in a critical condition. A view from the standpoint of pathophysiology

Better off breathing: an explanation for the seemingly detrimental impact of aerobic respiration on Zymomonas mobilis.

The bacterium Zymomonas mobilis is best known for fermentatively producing more ethanol than yeast. However, Z. mobilis has also puzzled researchers for decades with the counterintuitive observation that disrupting aerobic respiration benefits aerobic growth, implying that fermentation remains favorable. Retention of detrimental respiration genes seemed to defy natural selection. New findings by Felczak et al. help clarify the importance of respiration for Z. mobilis and the factors that led to the confusing prior results (M. M. Felczak, M. P. Bernard, and M. A. TerAvest, 2023, mBio 14:e02043-23, https://doi.org/10.1128/mbio.02043-23). The team overcame redundancy from multiple genome copies to delete what turned out to be a key terminal oxidase. Unlike previous studies, wherein mutants exhibited low respiration rates and had improved aerobic growth, this mutant was incapable of respiration and had poor aerobic growth. Thus, respiration is important but surprisingly exceeds what is optimal under lab conditions. Respiration likely protects against toxic effects of oxygen, ensuring retention of respiration genes in the Z. mobilis genome.

Hydrogen Production by CO2 Deprived Photoautotrophic Chlamydomonas reinhardtii Cultures.

Light-dependent hydrogen production by microalgae attracts attention of researchers because of the potential practical application. It is generally recognized that Calvin-Benson-Bassham cycle competes with hydrogen production process for electrons, and substrate (CO2) limitation of the cycle can increase hydrogen production rate. Furthermore, photosystem II is not destroyed by CO2 deficiency. We studied photoautotrophic cultures of Chlamydomonas reimhardtii under CO2 deficiency. Under the flow of air with removed CO2 the cultures reached stationary phase of growth and the photosystem II was downregulated due to overreduction of plastoquinone pool followed by degradation of the entire photosynthetic machinery. Under the Ar flow in the absence of CO2 the cultures were brought to microaerobic conditions producing small amounts of hydrogen (5 ml H2 day-1 liter-1 culture). Similar to the case of incubation under air atmosphere, prolonged incubation of cultures under microaerobic conditions resulted in down-regulation of photosystem II due to overreduction of plastoquinone pool with following degradation of whole photosynthetic machinery. Following removal of CO2, transfer of cultures into dark anaerobic conditions (2.5 h), and illumination with low-intensity light resulted in the cultures producing H2 with high initial rate. Total microalgal hydrogen production under these conditions was 56 ml H2 liter-1 culture. Thus, the CO2-deprived photoautotrophic cultures produce hydrogen. Hydrogen production was limited by the toxic effect of oxygen on hydrogenase but not by the Calvin-Benson-Bassham cycle competition with hydrogen production process.

Pathophysiological aspects of oxygen, hypoxia and free radical oxidation in critical conditions

Oxygen is the main regulator of metabolic processes in the body not only in the context of normal physiology, but also in the development of various critical conditions.
 In recent years, the problem of pathogenesis of a number organs' and systems' diseases has been enriched by knowledge of the mechanism of damage to cellular structures. Oxygen turned out to be the main factor of damage the very oxygen, due to the lack of which cell death occurs. It turned out that the so-called reactive oxygen species having an unpaired electron have a biological effect, which, depending on the concentration, can be regulatory or, conversely, toxic. Accordingly, interest has also been aroused in compounds that normally prevent the toxic effect of reactive oxygen species antioxidants. Today it is generally recognized that oxidative stress plays an important and possibly a key role in the pathogenesis of critical conditions. Thus, on the one side, excessive production of free radicals is considered as one of the manifestations of the body's protective reaction to the effects of various environmental factors and living conditions (infections, injuries, toxins, ionizing radiation, physical stress, hypothermia, hypoxia, various types of stress), on the other ― increased production of free radicals quickly leads to irreversible damage: destruction of the erythrocytes' membranes with subsequent hemolysis, transformation of hemoglobin into methemoglobin, DNA damage, desensitization of plasma membrane receptors, inactivation of various hormones and enzymes, including antiradical and antiperoxide protection enzymes.
 The problem of using oxygen in critical conditions is currently widely discussed in the periodical literature with an emphasis on the oxygen concentrations used in patients, both in operating rooms and in intensive care units. Oxygen used in the intensive care of acute respiratory failure and hypoxia should have a certain concentration range. The toxic effects of oxygen can occur with its prolonged use in high concentrations, which causes not only its direct toxic effect on the lungs, but also in the potentiation of the activation of free radical oxidation and excessive production of reactive oxygen species.
 The review presents current data on the physiological role of oxygen, its participation in metabolic processes against the background of inflammation, hypoxia and under conditions of activation of free radical oxidation processes. The recent approach to oxygen therapy and the research data presented in the review urge to relate to oxygen as a drug in order to avoid manifestations of its toxic effects.

PHYSIOLOGICAL SUBSTANTIATION OF DETERMINING THE RESISTANCE OF DIVERS TO THE TOXIC EFFECT OF OXYGEN USING ORAL STRESS RENAL TESTS

Aim of the work: to identify changes in renal function under the action of dosed hyperoxia using oral stress renal tests and to determine the relationship between the state of the functions of the excretory system and the body’s resistance to toxic effects of oxygen.Materials and methods. A survey of 44 men was carried out. Changes in water-electrolyte metabolism and renal function were determined using developed oral renal stress tests. Results and discussion. It has been shown that the normal functioning of the excretory system plays an important role in the high human resistance to the toxic effects of oxygen.

Underground construction: working in high pressure compressed air

Working in compressed air is a well recognised technique for tunnelling in soft, wet ground. This paper describes techniques for working in pressures of up to 15 bar, significantly above normal statutory limits. For health and safety reasons, working at such pressures requires the use of mixed-gas breathing mixtures and saturation exposure techniques. It requires a much greater knowledge of hyperbaric physiology than traditional compressed air work because of the toxic effects of oxygen and the narcotic effect of nitrogen at such pressures. The risks and mitigation measures for high-pressure work are explained.

Functional tests as an important direction of divers’ health preservation

Based measures to assess the candidates in divers, divers, caissons and other people at hyperbaric gas and water environments, special professionally important physiological functions. The recommended tests: check the functional state of divers during examination of barofunction; assessment of resistance to decompression intravascular gas formation; toxic effects of oxygen, narcotic effects of nitrogen, hypoxic.

DIAGNOSTIC AND TREATMENT CHARACTERISTICS OF LEPTOTHRICHOSIS OF THE ORAL MUCOSA

Leptotrichia species play an important role in the microflora composition of the oral cavity, a genus of asporogenous gram-negative anaerobic bacteria, in the form of sticks that belong to the family of Fusobakterium. According to the morphological data, the structure of the cell wall, antigenic structure, they are part of the opportunistic flora of the oral cavity. Their peculiarities are the sensitivity to the toxic effects of oxygen, the absence of spores, the complexity of food processes. It also allows to refer them to the family of lactic acid bacteria that promote lactic acid fermentation.
 Violation of homeostasis in the oral cavity and the presence of somatic diseases lead to the transformation of leptotrichia from the category of opportunistic microflora into pathogenic one. Different opinions about approaches to treatment in the presence of leptotrichia in the oral cavity are expressed. Some authors say that abundantly vegetative leptotrichia do not indicate pathology. Others, on the contrary, have the opposite view, believing that leptotrichosis is a disease close to opportunistic mycosis. But there is the third opinion: some authors attribute leptotrichosis to HIV - associated diseases. Clinical similarities with other fungal infections make it difficult to manage these patients.
 There are some important traits for differential diagnosis such as identified symptoms, in some cases the lack of effectiveness of previous or current treatment, postponed and concomitant diseases, sociodemographic status, use of medicines. Subjective, objective and additional examination methods were used for diagnosis.
 Objective examination of patients was carried out according to the recommendations of experts of the World Health Organization (WHO).
 As additional method of examination it has been used microscopic research, which was the most effective, clinical analysis of blood, urine, blood for sugar. If necessary, patients were referred for consultation to other specialists. Candidiasis of the oral mucosa has a code ICD - B.370.
 Patients have such complaints as burning of the mucous membrane of the lips, cheeks, hard and soft palate, dry mouth. There is a coarse keratinized epithelium of filamentous papillae, which gives them the appearance of spiky, pointed, very dense growths of gray or yellowish-gray color. The plaque may cover some areas of the oral mucosa. It adheres tightly to the tissues, is difficult to remove, exposing a loose bleeding surface. Inflammation is not identified. The mucous membrane appearance is worried patients, they examine it several times a day, which causes a phobia.
 In some cases, the filamentous papillae of the tongue may be atrophied, it becomes smooth, but the color of the mucosa is not changed. Patients suffer from eating spicy food.
 Among all diagnostic methods (subjective and objective) only the microscopic one is effective. Leptotrichosis accounts for 5 cases (4.09%) of the examined 122 patients with fungal origin stomatitis. This disease is quite rare, only a few clinical cases are described in the literature.
 The pathogenesis of the disease (incomplete cellular immunity, shift of the phagocytic activity of neutrophils, monocytes, eosinophils, the host sensitization of leptotrichia’s byproducts, high saccharolytic activity, and others) is considered in leptotrichosis management. Leptotrichosis of the oral cavity mucosa is characterized by a chronic course (for several months). The treatment plan is made with an internist. A dentist has to know different alternative kind of treatment. Patients should be examined dynamically.

A Disruptive Treatment to Prevent Amputation and Enhance Limb Salvage in an Elderly Patient

Background: Chronic wounds are a growing problem internationally, termed a silent epidemic. To combat this epidemic, it is not sufficient to rely on traditional wound care treatments alone, but to look to innovative and alternative therapies. The indispensable role of oxygen in wound healing is well-discussed in the literature, and in the past two decades the topical application of oxygen has shown promising results in the healing of chronic wounds. However, the toxic effects of oxygen are usually not appreciated and can often lead to wound necrosis and gangrene in wounds with compromised blood supply. While wounds with adequate blood supply contain free radical quenchers (catalase, superoxide dismutase and reduced glutathione) which neutralize the free radicals (reactive oxygen species) released as a by-product of the Krebs cycle, wounds with deficient blood supply are deficient in free radical quenchers and are further damaged by exposure to oxygen as a result of reperfusion injury/oxygen toxicity. Topical hyperbaric oxygen (THOT&#174) uses low oxygen tensions in the hyperbaric range to stimulate angiogenesis, while preventing excessive oxygen toxicity. The result is the induction of marked angiogenesis, with increasing capacity for quenching reactive oxygen species, resulting in wound healing of ischemic wounds. Case Presentation: This case report describes a 95-year-old Caucasian female who presented with a stage IV chronic necrotic ulcer on her lower left leg. Surgical pathology results revealed calcifying vasculopathy, which is thought to be responsible for deficient blood supply to the leg, leading to a necrotic, chronic leg ulcer of her left leg. After traditional wound therapies were unsuccessful, she was considered for leg amputation. The introduction of adjunctive treatment with topical hyperbaric oxygen therapy saw complete healing of the wound within 15 weeks. The wound remained closed, without the presence of scar tissue, with no signs of wound breakdown at three-month and six-month follow-ups. Conclusions: Chronic hypoxic wounds with vascular insufficiency are considered “unlikely to heal” and tend to lead to limb amputation. The use of THOT&#174 technology, with low hyperbaric oxygen tensions to neutralize free radicals released by the Krebs cycle when oxygen contacts the wound, prevents oxygen toxicity and results in angiogenesis necessary for wound healing. In this way, THOT&#174 treatment was able to convert the hypoxic “unlikely to heal” wound considered for limb amputation into one which healed, with limb salvage. The results of this case report demonstrate the potential for complete healing of chronic hypoxic wounds even in complex cases with multiple confounding factors preventing wound healing, using a cost-effective treatment that is easily accessible to patients.

Normothermic Machine Perfusion Using an Air/Oxygen Mixer: Reconditioning a Marginal Donor Liver

Background: The use of marginal livers or extended criteria donors (ECD) represents the concrete possibility of expanding the pool of available organs for transplantation, and reducing the discrepancy between the demand for organs and the number of donations. Sub-optimal grafts are more susceptible to ischemia-reperfusion (IR) injury during static-type cold storage (SCS). In this setting, machine perfusion (MP) is increasingly used as a promising alternative to SCS, offering better preservation of the liver parenchyma compared with the standard method of organ preservation. Methods: In reported cases there is a high incidence of hyperoxia and respiratory alkalosis in the perfusate, with consequent concerns about the toxic effect of oxygen, and alteration of cellular homeostasis. For this reason, we have gradually focused our attention on the use of oxygen during reconditioning of the liver, though with the use of an added latest-generation oxygenator. Results: We present the first reported combined use of normothermic machine perfusion liver assist (LA) and the Sechrist 3500 Air/Oxygen Mixer, aimed at better controlling and regulating the pO2 and CO2 in the process of reconditioning a marginal liver from an ECD. Conclusion: Based on our experience and a thorough review of the literature it seems that the use of a high accuracy fluximeter improves the procedure of reconditioning. Further investigation should be directed to understand the effect of a more physiologic perfusate gas content.

Estresse oxidativo na interrupção da ventilação mecânica em pacientes vítimas de traumatismo cranioencefálico: um estudo randomizado e cego

Introdução: Os efeitos tóxicos do oxigênio não estão bem estabelecidos em seres humanos. Objetivo: Analisar os níveis de estresse oxidativo (EOx) na interrupção da ventilação mecânica (VM) em pacientes vítimas de TCE. Métodos: Estudo prospectivo, longitudinal, analítico, randomizado e cego. Participaram 12 pacientes: PSV (n=6) e grupo Tubo-T (n=6). A interrupção da VM deu-se em: PSV- (Δ 7 cmH2O) e PEEP (5 cmH2O) durante 30 minutos; Tubo-T - o paciente foi conectado ao tubo T com FiO2 a 0,4 durante 30 minutos. Realizou-se avaliação morfológica do EOx no plasma sanguíneo pelo Dry layer oxidative test. A coleta foi realizada: com 24h de VM, antes do teste, em 15’ de teste e após o teste PSV ou Tubo-T. Para análise da normalidade utilizou-se o teste de Shapiro-Wilk para análise intragrupo e intergrupos, o teste ANOVA seguido de Tukey; para correlação-Correlação de Spearman (p valor 5%). Resultados: Não houve aumento estatisticamente significativo na descontinuidade da matriz extracelular nos grupos (p>0,05). Os níveis de EOx encontraram-se elevados (grau III–moderado) nas primeiras avaliações. Não foi encontrada correlação significativa entre os parâmetros de VM com o EOx. O grupo PSV permaneceu em média 12.33 dias sob VM, tendo EOx de 29.02 (grau III/ moderado) – r=0.8, p=0.01; o grupo Tubo T em média 12.83±2.2 dias, tendo EOx de 31.03±5.41 (grau IV/grave)- r=0.9, p=0.07. Conclusão: Não houve diferença no comportamento do EOx entre os métodos de interrupção da VM. No entanto, o EOx aumentou com o tempo de VM.

NITROGEN MONOXIDE AS A FACTOR OF ACTIVATION OF THE PROOXIDANT SYSTEM ON THE BACKGROUND OF SUBSIDIES OF HIGH CONCENTRATIONS OF OXYGEN IN NEWBORNS WITH RESPIRATORY DISTRESS

Data about the peculiarities of metabolism of endogenous NO in modern literature are quite controversial, especially in newborns with respiratory distress who need artificial lung ventilation. Investigating of the peculiarities of peroxidation processes on the background of excessive accumulation of nitrogen monoxide metabolites due to the inhalation of different concentrations of oxygen among newborns with severe respiratory insufficiency.84 newborns who were admitted to the department of intensive care of newborns were under investigation. They were randomized into groups according to their oxygen saturation index of the inhaled mixture. The exhaled breath condensate was tested for nitrogen monoxide metabolites, malonic aldehyde, aldehyde and ketone derivatives of the 2,4-dinitrophenyl hydrazine of a neutral and basic (aggregates of protein molecules) nature.Obtained results indicated that nitrogen monoxide (active oxidant) directly affects the increase of activity of processes of proteins and lipids peroxidation by increasing the total oxidation potential. Excessive endogenous NO formation under the conditions of subsidizing of high concentrations of oxygen leads to an increase in excessive formation of nitrogen monoxide and is a risk factor for the initiation of oxidative stress processes.Thus, nitrogen monoxide is one of the factors of activation of free radical oxidation at the level of alveolar-capillary space among newborns with respiratory distress. In intensive care for newborns with severe respiratory failure, the use of excessive oxygen concentrations should be avoided, as on the background of increased endogenous NO formation, there is a risk factor for the toxic effect of oxygen on the biological structures due to the increased formation of active forms of oxygen with the development of oxidative stress.

Pathophysiological Aspects of Hyperoxia in Anesthesiologist-Reanimatologist's Practice

The aim of the review is to present potentially negative effects of hyperoxia in various groups of critically ill patients, including those after cardiac arrest, brain injury or stroke, and in cases of sepsis. It was noted that in cases of these pathological processes and nosological forms there were evidences that hyperoxia could have a damaging effect, and that oxygen should be prescribed on an individual basis depending on the assessment of the current oxy- gen requirement. It has been established that hyperoxia commonly represent the last reserve to abrogate the progressive hypoxia. The mechanisms of adaptation of the body to hyperoxia are described and the possibility to reduce the toxic effects of oxygen with the aid of succinates is discussed.

MOLECULES OF MIDDLE MASS AS AN INDICATOR OF DIVERS’ «HYPERBARIC INTOXICATION»

The aim of the study was to determine the content of the molecules of middle mass before and after a simulated «diving» in the blood plasma of subjects who had different initial resistance to decompression sickness, toxic effect of nitrogen and oxygen. An increase in the concentration of the middle mass molecules was revealed after a simulated dive in a pressure chamber in the blood plasma of subjects who were unstable to the adverse effects of hyperbaric factors. The changes discovered are the most prominent in the development of decompression gas-generation and toxic effect of oxygen. Unidirectional action of unfavorable hyperbaric factors was shown to induce human endogenous intoxication with possible development of the syndrome of «hyperbaric intoxication».

The medical use of oxygen: a time for critical reappraisal

Oxygen treatment has been a cornerstone of acute medical care for numerous pathological states. Initially, this was supported by the assumed need to avoid hypoxaemia and tissue hypoxia. Most acute treatment algorithms, therefore, recommended the liberal use of a high fraction of inspired oxygen, often without first confirming the presence of a hypoxic insult. However, recent physiological research has underlined the vasoconstrictor effects of hyperoxia on normal vasculature and, consequently, the risk of significant blood flow reduction to the at-risk tissue. Positive effects may be claimed simply by relief of an assumed local tissue hypoxia, such as in acute cardiovascular disease, brain ischaemia due to, for example, stroke or shock or carbon monoxide intoxication. However, in most situations, a generalized hypoxia is not the problem and a risk of negative hyperoxaemia-induced local vasoconstriction effects may instead be the reality. In preclinical studies, many important positive anti-inflammatory effects of both normobaric and hyperbaric oxygen have been repeatedly shown, often as surrogate end-points such as increases in gluthatione levels, reduced lipid peroxidation and neutrophil activation thus modifying ischaemia-reperfusion injury and also causing anti-apoptotic effects. However, in parallel, toxic effects of oxygen are also well known, including induced mucosal inflammation, pneumonitis and retrolental fibroplasia. Examining the available 'strong' clinical evidence, such as usually claimed for randomized controlled trials, few positive studies stand up to scrutiny and a number of trials have shown no effect or even been terminated early due to worse outcomes in the oxygen treatment arm. Recently, this has led to less aggressive approaches, even to not providing any supplemental oxygen, in several acute care settings, such as resuscitation of asphyxiated newborns, during acute myocardial infarction or after stroke or cardiac arrest. The safety of more advanced attempts to deliver increased oxygen levels to hypoxic or ischaemic tissues, such as with hyperbaric oxygen therapy, is therefore also being questioned. Here, we provide an overview of the present knowledge of the physiological effects of oxygen in relation to its therapeutic potential for different medical conditions, as well as considering the potential for harm. We conclude that the medical use of oxygen needs to be further examined in search of solid evidence of benefit in many of the current clinical settings in which it is routinely used.

It’s time to pay attention to the endometrium

The physiologic importance of the endometrium in assisted reproductive technology is now receiving much research attention. The historical importance of ultrasound for determination of endometrial pattern, thickness and contractility is reviewed and speculation provided for a possible mechanism of the adverse effect of thin endometrium on implantation.

Oxygen Use for Preterm Infants

Preterm infants in neonatal intensive care units frequently require oxygen therapy. Clinicians are responsible for titrating oxygen to maximize the benefits and minimize the risks of this therapy. Studies have identified various toxic effects of oxygen on the developing tissues of the preterm infant; however, optimal target SpO(2) ranges have not been identified. Current trends in neonatology are focusing on defining optimal oxygen saturation ranges to improve infant outcomes and to decrease complications associated with the oxygen use. Consequently, research-based guidelines are being developed in neonatal intensive care units to guide oxygen administration. As target oxygen saturation ranges are developed, issues regarding health care professional compliance with these ranges have been identified. The specific reasons for this noncompliance have not been widely explored. However, factors such as nursing shortages, staffing issues, and a de-emphasis on staff education surrounding oxygen use have been offered as possible reasons. Understanding factors shaping clinical decision-making about oxygen titration is critical when designing policies and educational programs to change oxygen titration practice and ultimately improve patient outcomes. In this article, the literature outlining the importance of oxygen titration for preterm infants is reviewed. Discussion then focuses on factors that influence clinical decision-making and how these factors may influence decisions surrounding the use of oxygen for preterm infants.

Rapid-Onset Acute Respiratory Distress Syndrome (ARDS) in a Patient Undergoing Metastatic Liver Resection: A Case Report and Review of the Literature

Metastatic liver resection following cytoreductive chemotherapy is an accepted treatment for oligometastatic tumor diseases. Although pulmonary complications are frequently reported in patients undergoing liver surgery including liver transplantation, life-threatening acute respiratory failures in the absence of aspiration, embolism, transfusion-related acute lung injury (TRALI), pulmonary infection, or an obvious source of systemic sepsis are rare. We performed an extensive clinical review of a patient undergoing metastatic liver resection who had a clinical course compatible to an acute respiratory distress syndrome (ARDS) without an obvious cause except for the surgical procedure and multiple preoperative chemotherapies. We hypothesize that either the surgical procedure mediated by cytokines and tumor necrosis factor or possible toxic effects of oxygen applied during general anesthesia were associated with life-threatening respiratory failure in the patient. Discrete and subclinical inflammated alveoli (probably due to multiple preoperative chemotherapies with substances at potential risk for interstitial pneumonitis as well as chest radiation) might therefore be considered as risk factors.

Blood gas targets

Blood gas measurements i.e. measurement of the levels of oxygen and carbon dioxide in arterial blood, are important parameters for critical care of sick newborns. Oxygen is one of the most commonly used as well as misused drugs in the neonatal intensive care units. Rapidly changing physiology, difficulty in access to arterial sampling sites, and small blood volumes in newborns at times present unique challenges to the treating neonatologist. Studies have shown that the use of supplemental oxygen in neonatal care may result in both significant health care benefits and harms; till date uncertainty remains as to the most appropriate range to target blood oxygen levels in preterm and low birth weight infants. Unnecessary use of oxygen in newborn babies leads to oxidative stress and damage to various organ-systems, particularly lungs, brain and eyes. Preterm newborns are most vulnerable to the toxic effects of oxygen due to their limited antioxidant defenses. There are numerous causes of hypoxia in newborns but there is only one cause of hyperoxia, namely, giving too much oxygen than what is really needed (iatrogenic). It is essential that all health professionals looking after newborn babies are sensitized to the dangers posed by hyperoxia and change their clinical practice to limit oxygen exposure in this vulnerable population.

In vitro culture under physiologic oxygen concentration improves blastocyst yield and quality: a prospective randomized survey on sibling oocytes

A prospective randomized study was carried on sibling oocytes in which human gametes and embryos were cultured at physiologic (6% CO(2) + 5% O(2) + 89% N(2)) condition from insemination to day 6 or at atmospheric (6% CO(2) in air) condition until day 3 and at physiologic environment afterward. The results showed that physiologic oxygen concentration throughout culture period improved total blastocyst yield and day 5 embryo quality.