Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Heavy metals are naturally occurring elements that have a high atomic weight and a density at least five times greater than that of water. Their multiple industrial, domestic, agricultural, medical, and technological applications have led to their wide distribution in the environment, raising concerns over their potential effects on human health and the environment. Their toxicity depends on several factors including the dose, route of exposure, and chemical species, as well as the age, gender, genetics, and nutritional status of exposed individuals. Because of their high degree of toxicity, arsenic, cadmium, chromium, lead, and mercury rank among the priority metals that are of public health significance. These metallic elements are considered systemic toxicants that are known to induce multiple organ damage, even at lower levels of exposure. They are also classified as human carcinogens (known or probable) according to the US Environmental Protection Agency and the International Agency for Research on Cancer. This review provides an analysis of their environmental occurrence, production and use, potential for human exposure, and molecular mechanisms of toxicity, genotoxicity, and carcinogenicity.

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Heavy metal toxicity and the environment.

Heavy metal toxicity has proven to be a major threat and there are several health risks associated with it. The toxic effects of these metals, even though they do not have any biological role, remain present in some or the other form harmful for the human body and its proper functioning. They sometimes act as a pseudo element of the body while at certain times they may even interfere with metabolic processes. Few metals, such as aluminium, can be removed through elimination activities, while some metals get accumulated in the body and food chain, exhibiting a chronic nature. Various public health measures have been undertaken to control, prevent and treat metal toxicity occurring at various levels, such as occupational exposure, accidents and environmental factors. Metal toxicity depends upon the absorbed dose, the route of exposure and duration of exposure, i.e. acute or chronic. This can lead to various disorders and can also result in excessive damage due to oxidative stress induced by free radical formation. This review gives details about some heavy metals and their toxicity mechanisms, along with their health effects.

https://sciendo.com/pdf/10.2478/intox-2014-0009

Toxicity, mechanism and health effects of some heavy metals

Advances in metal-induced oxidative stress and human disease

Exposure to heavy metals is a common phenomenon due to their environmental pervasiveness. Metal intoxication particularly neurotoxicity, genotoxicity, or carcinogenicity is widely known. This review summarizes our current understanding about the mechanism by which metalloids or heavy metals (particularly arsenic, lead, cadmium and mercury) induce their toxic effects. The unifying factor in determining toxicity and carcinogenicity for all these metals is the generation of reactive oxygen and nitrogen species. The toxic manifestations of these metals are caused primarily due to imbalance between pro-oxidant and antioxidant homeostasis which is termed as oxidative stress. Besides these metals have high affinity for thiol groups containing enzymes and proteins, which are responsible for normal cellular defense mechanism. Long term exposure to these metals could lead to apoptosis. Signaling components affected by metals include growth factor receptors, G-proteins, MAP kinases and transcription factors. Chelation therapy with chelating agents like calcium disodium ethylenediamine tetra acetic acid (CaNa(2)EDTA), British Anti Lewisite (BAL), sodium 2,3-dimercaptopropane 1-sulfonate (DMPS), meso 2,3-dimercaptosuccinic acid (DMSA) etc., is considered to be the best known treatment against metal poisoning. Despite many years of research we are still far away from effective treatment against toxicity caused due to exposure to heavy metals/metalloids. The treatment with these chelating agents is compromised with number of serious side-effects. Studies show that supplementation of antioxidants along-with a chelating agent prove to be a better treatment regimen than monotherapy with chelating agents. This review attempts a comprehensive account of recent developments in the research on heavy metal poisoning particularly the role of oxidative stress/free radicals in the toxic manifestation, an update about the recent strategies for the treatment with chelating agents and a possible beneficial role of antioxidants supplementation to achieve the optimum effects. We have selected only arsenic, lead, mercury and cadmium for this article keeping in view current concerns and literature available.

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Heavy metal induced oxidative stress & its possible reversal by chelation therapy.

Chelation therapy is the preferred medical treatment for reducing the toxic effects of metals. Chelating agents are capable of binding to toxic metal ions to form complex structures which are easily excreted from the body removing them from intracellular or extracellular spaces. 2,3-Dimercaprol has long been the mainstay of chelation therapy for lead or arsenic poisoning, however its serious side effects have led researchers to develop less toxic analogues. Hydrophilic chelators like meso-2,3-dimercaptosuccinic acid effectively promote renal metal excretion, but their ability to access intracellular metals is weak. Newer strategies to address these drawbacks like combination therapy (use of structurally different chelating agents) or co-administration of antioxidants have been reported recently. In this review we provide an update of the existing chelating agents and the various strategies available for the treatment of heavy metals and metalloid intoxications.

http://www.tracemin.com/fileadmin/uploads/pdf/en/Chelation_in_Metal_Intoxication.pdf

Chelation in Metal Intoxication

Arsenic-induced oxidative stress and its reversibility

Oxidative stress contributes to the pathophysiology of exposure to heavy metals/metalloid. Beneficial renal effects of some medications, such as chelation therapy depend at least partially on the ability to alleviate oxidative stress. The administration of various natural or synthetic antioxidants has been shown to be of benefit in the prevention and attenuation of metal induced biochemical alterations. These include vitamins, N-acetylcysteine, α-lipoic acid, melatonin, dietary flavonoids and many others. Human studies are limited in this regard. Under certain conditions, surprisingly, the antioxidant supplements may exhibit pro-oxidant properties and even worsen metal induced toxic damage. To date, the evidence is insufficient to recommend antioxidant supplements in subject with exposure to metals. Prospective, controlled clinical trials on safety and effectiveness of different therapeutic antioxidant strategies either individually or in combination with chelating agent are indispensable. The present review focuses on structural, chemical and biological aspects of antioxidants particularly related to their chelating properties.

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Structural, chemical and biological aspects of antioxidants for strategies against metal and metalloid exposure.

Over the past few decades, free radicals, highly reactive and thereby destructive molecules, are known increasingly for their importance to human health and disease. Many common and life threatening human diseases, including atherosclerosis, diabetes, cancer, and aging, have free radical reactions as an underlying mechanism of injury. Because our body is continuously exposed to free radicals and other ROS, from both external sources (sunlight, other forms of radiation, pollution) and generated endogenously, ROS-mediated tissue injury is a final common pathway for a number of disease processes. Radicals of oxygen (superoxide anion, hydroxyl radical, and peroxy- radicals), reactive non-radical oxygen species such as hydrogen peroxide and singlet oxygen, as well as carbon, nitrogen, and sulfur radicals comprise the variety of reactive molecules that can cause damage to cell. Our conceptual understanding of the interaction of such reactive oxygen species (ROS) with living organisms has undergone a remarkable evolution. 
Antioxidants are intimately involved in the prevention of cellular damage - the common pathway for cancer, aging, and a variety of diseases. These molecules safely interact with free radicals and terminate the chain reaction before vital molecules are damaged. They neutralize free radicals by donating one of their own electrons. The antioxidant nutrients themselves don㆒t become free radicals by donating an electron because they are stable in either form; they act as scavengers, helping to prevent cell and tissue damage that could lead to cellular damage and disease. Although there are several enzyme systems within the body that scavenge free radicals, the principle antioxidants are vitamin E, vitamin C, n-acetylcysteine and -lipoic acid. The vitamins C and E are thought to protect the body against the destructive effects of free radicals. Additionally, selenium, a trace metal that is required for proper function of one of the body's antioxidant enzyme systems, is also included in this category. 
After having a very successful symposium during the Fourth World Congress on Cellular and Molecular Biology held at Poieters Prof. Maixent and I decided to have a special issue of Cellular and Molecular Biology covering the different topics related to role of free radicals in different human diseases/ poisonings and possible effects of antioxidants. We included reviews and free papers covering the patho-biology of free radicals in a wide range of diseases afflicting large section of population such as diabetes, cardio-vascular diseases; some others would focus on fundamental aspects. There are research articles that would also delve into the progress made by toxicologists. 
The first article of the first issue by Ray et al. focuses on some of the current areas of nitric oxide (NO) research, recent understanding on the novel actions of this molecule, state of the art in developing drugs that works through NO and speculate on future research directions. The second article by Korkina describes the metabolic pathways of phenylpropanoid biosynthesis in plants and the mechanism of phenylpropanoid-mediated plant defense. Third article by us provides comprehensive information about the role of oxidative stress in lead and arsenic toxicity and possible remedial measures (i.e. role of antioxidants and chelating agents). After these three review papers there are number of original research papers. The first paper by Sharma et al. provides information that N- acetyl cysteine (NAC), attenuates1-methyl 4-phenyl-1, 2, 3, 6 tetrahydropyridine (MPTP) neurotoxicity in mice brain and this protection by the NAC might be contributing to the regeneration of GSH, a major antioxidant. The study by Yang et al shows that intracellular redox state may not be an important cause of the metal induced cytotoxicity but a depletion of GSH may enhance metal toxicity. Kostyuk et al. suggested the crucial role of oxidative stress in Thioacetamide-induced hepatotoxicity and also suggest protective effect of rutin-iron complex. An interesting study by Husain suggested that chronic ethanol ingestion induces aortic endothelial oxidative injury and the down regulation of nitric oxide generating system leading to impaired vasorelaxation and hypertension in rats. An important finding by Zoltani and Baskin reported that control of the swelling and protein kinase C (PKC)-activated chloride currents can limit the electrical chaos of pharmacologically-caused hypoxic cardiac toxicity. Chatterjee et al. investigated the NO/NOS status and superoxide radical generation from neutrophils in spontaneously hypertensive rats to assess the role of neutrophils and oxidative stress in hypertension and suggested that macrophages can possibly play a role in target organ damage during hypertension as they do in sepsis. An important contribution by De Luca et al. suggested that pre- and post oral administration with selected antioxidants (RRR-a-tocopherol, coenzyme Q10) potentiating antioxidant defence system, coupled with enhancers of a specific immune defense (soy phospholipids, L-methionine), is beneficial to skin healing and trophism. The last article of the first issue by Bhadauria et al. studied the cytotoxic effect Isoniazid (INH) in hepatoma cell line (Hep-G2). 
Thus the special issue provides valuable information for researchers working in the area of oxidative stress and antioxidants. I sincerely thank all contributors for submitting their manuscripts in a timely manner and working diligently with the editors. I would also like to thank my two co-editors, Dr (Mrs.) Madhu Dikshit and Dr Govinder Flora for providing me whole hearted support in the review process and Dr. R. Vijayaraghavan, Director, Defence Research and Development Establishment, Gwalior, India for his co-operation and support. We also thank Prof. Maixent and Prof. Wegmann for giving us an opportunity to contribute two special issues of Cellular and Molecular Biology on the above theme and also all the staff (particularly Mourad FARES) for their support and co-operation.

Swaran J.S. Flora

Papers

Heavy metal induced oxidative stress & its possible reversal by chelation therapy.

Chelation in Metal Intoxication

Arsenic-induced oxidative stress and its reversibility

Structural, chemical and biological aspects of antioxidants for strategies against metal and metalloid exposure.

Role of free radicals and antioxidants in health and disease.