scholarly journals Comparative analysis of two L-carnitine preparations and their concentration effects on CAT expression in healthy human peripheral blood lymphocyte cultures

2021 ◽  
Vol 5 (2) ◽  
pp. 10
Author(s):  
Maja Kuzmanovic ◽  
Naida Lojo-Kadric ◽  
Jasmin Ramic ◽  
Anja Haveric ◽  
Sanin Haveric ◽  
...  

CAT gene encodes catalase, a key antioxidant enzyme in the body against oxidative stress. This enzyme plays an important role in the molecular mechanisms of inflammation, apoptosis, mutagenesis and tumorigenesis. Anti-oxidant L-carnitine is used in food supplementation, medical co-treatment and bodyweight regulation. We aimed to investigate molecular basis of L-carnitine commercial preparations supplementation in reducing oxidative stress with customized CAT gene assay in vitro. Human lymphocytes cell culture was established using standard procedure and treated with range of concentrations of L-carnitine in two preparations. We tested two preparations: 500 mg tablets of L-carnitine and liquid L-carnitine with vitamin B6. L-carnitine significantly reduced the expression of CAT gene in cultured lymphocytes at concentrations of 50 μmol/l and 250 μmol/l compared to negative control, (p = 0,001; p = 0,001; respectively). The L-carnitine liquid supplement with vitamin B6 also reduced the transcription of CAT gene at concentrations of 50 μmol/l and 250 μmol/l as compared to the negative control (p = 0,018; p = 0,006; respectively). Selected L-carnitine preparations modulated the transcriptional activity of the antioxidant enzyme gene in human lymphocyte culture, indicating its possible effects in inhibition of pro-inflammatory processes that involve catalase activity.

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Hang Wang ◽  
Wayne Lau ◽  
Erhe Gao ◽  
Walter Koch ◽  
Xin Ma ◽  
...  

Myocardial ischemic/reperfusion (MI/R) injury is significantly enhanced in diabetes by incompletely understood mechanisms. Recent clinical and experimental studies demonstrate that hypoadiponectinemia during diabetes enhances oxidative stress and exaggerates MI/R injury. However, molecular mechanisms responsible for hypoadiponectinemia-induced oxidative stress remain unknown. In a discovery-driven fashion, we determined the role of cardiac microRNAs in the MI/R response in adiponectin knockout (APNKO) mice. From 68 total miRNAs differentially expressed between APNKO and wild type (WT) mice, miRNA 449b was identified as the microRNA most relevant to oxidative stress and apoptosis. In cultured neonatal cardiomyocytes, miRNA 449b silencing inhibited hypoxia/reoxygenation-induced apoptosis, whereas miR-449b overexpression significantly increased oxidative stress and cardiomyocyte apoptosis. In APNKO mice, administration of anti-miR-449b decreased oxidative stress (-17.2±3.8%, p<0.05), reduced caspase-3 activity (-21.3±4.2%, p<0.05), attenuated myocardial apoptosis (-16.3±4.1%, p<0.05), and improved myocardial function (1.4±0.3 fold). To identify the downstream molecule regulated by miRNA 449b, we integrated transcriptomics and proteomics data with computational annotation data, and identified Nrf-1 as a miRNA 449b target. A luciferase reporter gene assay demonstrated that miRNA 449b inhibited Nrf-1 expression via Nrf-1 mRNA 3’UTR region binding. Finally, we demonstrated that miRNA 449b was significantly upregulated, Nrf-1 expression was significantly decreased, and the anti-oxidative molecule metallothionein (MT) was significantly inhibited in the diabetic heart subjected to MI/R. Administration of anti-miR-449b in diabetic animals upregulated Nrf-1 and MT expression, reduced oxidative stress, and improved cardiac function (P<0.01) after MI/R. Taken together, this study provides the first evidence that hypoadiponectinemia during diabetes causes cardiac miRNA-449b upregulation and subsequent downregulation of Nrf-1 and MT, thus enhancing oxidative stress and MI/R injury. MicroRNA 449b may represent a potential therapeutic target against diabetic heart disease.


2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Ting Li ◽  
Yanhong Huang ◽  
Wenkai Zhou ◽  
Qichang Yan

Background. Oxidative stress is an important factor during age-related cataract formation. Apoptosis and autophagy induced by oxidative stress have been reported as key factors in age-related cataract. In our research, we investigated the role of let-7c-3p in the regulation of autophagy and apoptosis during the formation of age-related cataract. Material and Methods. Real-time PCR and western blot were employed to detect the expression of let-7c-3p in the tissues of age-related cataract. Human lens epithelial cells (LECs) were treated with H2O2 as an age-related cataract model. The extent of apoptosis was measured by flow cytometry and western blot. To detect autophagy, immunofluorescence was used to analyze the spot number of LC3, and western blot was used to detect the expression of LC3-II/I and ATG3. The molecular mechanisms of let-7c-3p regulating autophagy via ATG3 under oxidative stress were performed by a luciferase report gene assay and rescue experiment. Results. Downregulation of let-7c-3p was found in the age-related cataract group aged >65 years relative to the age-related cataract group aged ≤65 years. Consistently, the expression of let-7c-3p was also lower under oxidative stress. The activities of LEC apoptosis and autophagy induced by oxidative stress were inhibited by let-7c-3p. By the bioinformatics database and the luciferase reporter assay, ATG3 was found to be a direct target of let-7c-3p. Let-7c-3p reduced the ATG3-mediated autophagy level, which was induced by oxidative stress in LECs. Conclusion. Let-7c-3p inhibits autophagy by targeting ATG3 in LECs in age-related cataract.


2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Zhanpeng Wang ◽  
Zhuonan Li ◽  
Yanshuo Ye ◽  
Lijuan Xie ◽  
Wei Li

Accumulating evidence has indicated that oxidative stress (OS) is associated with the development of hepatocellular carcinoma (HCC). However, the mechanisms remain largely unknown. Normally, OS occurs when the body receives any danger signal—from either an internal or external source—and further induces DNA oxidative damage and abnormal protein expression, placing the body into a state of vulnerability to the development of various diseases such as cancer. There are many factors involved in liver carcinogenesis, including hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, alcohol abuse, and nonalcoholic fatty liver disease (NAFLD). The relationship between OS and HCC has recently been attracting increasing attention. Therefore, elucidation of the impact of OS on the development of liver carcinogenesis is very important for the prevention and treatment of liver cancer. This review focuses mainly on the relationship between OS and the development of HCC from the perspective of cellular and molecular mechanisms and the etiology and therapeutic targets of HCC.


Author(s):  
Sara Gonçalves ◽  
Isabel Gaivão

The term cosmetics refers to a product applied to the body for the purpose of beautifying, cleansing or improving appearance and enhancing attractive features. The natural cosmetics market has grown since the consumer took consciousness of the concept of natural-based ingredients. A great number of cosmetics have noxious and chemically-potent substances and have an ecological impact on the environment. A study performed by the Danish Council THINK Chemicalsfound that in total 65 chemicals of concern were found in 39 products. This means consumers are exposed to these chemicals, perhaps in a daily basis. They also found that three products contained illegal ingredients in the European Union. Thus, the use of natural and organic cosmetics becomes increasingly important. This requires a strong investigation into the benefits that fruits and plants can bring to health. The PhD project will focus on four natural ingredients common in the Trás-os-Montes area: almond (Prunus dulcis), elderberry (Sambucus nigra), olive (Olea europaea) and grapes (Vitis vinifera). The general purpose of this PhD project is to evaluate the cosmetic properties of the natural ingredients towards the DNA integrity promotion. Additionally, it is intended to evaluate genoprotection, longevity and prolificacy of the natural ingredients in Drosophila melanogaster. The short life cycle, the distinct developmental stages, the availability of various tools and reagents, known genome sequence and the physiological similarity of Drosophila with humans make them an excellent in vivo model organism to rapidly test toxicity in whole organism and elucidate the molecular mechanisms underlying the toxicity. The natural product with the best result will be used to evaluate genoprotection in human lymphocytes. These are used as a surrogate tissue, as they are easily obtained, in large numbers, do not require cell culture, are diploids and are almost all in the same phase of the cell cycle. This project is in an initial phase and lacks results, which will be available along this year.


Antioxidants ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 164 ◽  
Author(s):  
Ananda S. Prasad ◽  
Bin Bao

The essentiality of zinc as a trace mineral in human health has been recognized for over five decades. Zinc deficiency, caused by diet, genetic defects, or diseases, can cause growth retardation, delayed sexual maturation, depressed immune response, and abnormal cognitive functions in humans. Zinc supplementation in zinc-deficient individuals can overcome or attenuate these abnormalities, suggesting zinc is an essential micro-nutrient in the body. A large number of in vitro and in vivo experimental studies indicate that zinc deficiency also causes apoptosis, cellular dysfunction, deoxyribonucleic acid (DNA) damage, and depressed immune response. Oxidative stress, due to the imbalance of reactive oxygen species (ROS) production and detoxification in the anti-oxidant defense system of the body, along with subsequent chronic inflammation, is believed to be associated with many chronic degenerative diseases such as diabetes, heart diseases, cancers, alcohol-related disease, macular degenerative disease, and neuro-pathogenesis. A large number of experimental studies including cell culture, animal, and human clinical studies have provided supportive evidence showing that zinc acts as an anti-oxidative stress agent by inhibition of oxidation of macro-molecules such as (DNA)/ribonucleic acid (RNA) and proteins as well as inhibition of inflammatory response, eventually resulting in the down-regulation of (ROS) production and the improvement of human health. In this article, we will discuss the molecular mechanisms of zinc as an anti-oxidative stress agent or mediator in the body. We will also discuss the applications of zinc supplementation as an anti-oxidative stress agent or mediator in human health and disease.


Animals ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. 462 ◽  
Author(s):  
Peter F. Surai ◽  
Ivan I. Kochish ◽  
Vladimir I. Fisinin ◽  
Darren T. Juniper

In commercial animals production, productive stress can negatively impact health status and subsequent productive and reproductive performance. A great body of evidence has demonstrated that as a consequence of productive stress, an overproduction of free radicals, disturbance of redox balance/signaling, and oxidative stress were observed. There is a range of antioxidants that can be supplied with animal feed to help build and maintain the antioxidant defense system of the body responsible for prevention of the damaging effects of free radicals and the toxic products of their metabolism. Among feed-derived antioxidants, selenium (Se) was shown to have a special place as an essential part of 25 selenoproteins identified in animals. There is a comprehensive body of research in monogastric species that clearly shows that Se bioavailability within the diet is very much dependent on the form of the element used. Organic Se, in the form of selenomethionine (SeMet), has been reported to be a much more effective Se source when compared with mineral forms such as sodium selenite or selenate. It has been proposed that one of the main advantages of organic Se in pig and poultry nutrition is the non-specific incorporation of SeMet into general body proteins, thus forming an endogenous Se reserve that can be utilized during periods of stress for additional synthesis of selenoproteins. Responses in ruminant species to supplementary Se tend to be much more variable than those reported in monogastric species, and much of this variability may be a consequence of the different fates of Se forms in the rumen following ingestion. It is likely that the reducing conditions found in the rumen are responsible for the markedly lower assimilation of inorganic forms of Se, thus predisposing selenite-fed animals to potential Se inadequacy that may in turn compromise animal health and production. A growing body of evidence demonstrates that organic Se has a number of benefits, particularly in dairy and beef animals; these include improved Se and antioxidant status and better Se transfer via the placenta, colostrum, and milk to the newborn. However, there is a paucity in the data concerning molecular mechanisms of SeMet assimilation, metabolism and selenoprotein synthesis regulation in ruminant animals, and as such, further investigation is required.


2021 ◽  
Vol 22 (11) ◽  
pp. 5479
Author(s):  
Slavko Komarnytsky ◽  
Thirumurugan Rathinasabapathy ◽  
Charles Wagner ◽  
Brandon Metzger ◽  
Carolina Carlisle ◽  
...  

The endocannabinoid system (ECS) consists of endogenous cannabinoids, their receptors, and metabolic enzymes that play a critical homeostatic role in modulating polyunsaturated omega fatty acid (PUFA) signaling to maintain a balanced inflammatory and redox state. Whole food-based diets and dietary interventions linked to PUFAs of animal (fish, calamari, krill) or plant (hemp, flax, walnut, algae) origin, as well as full-spectrum hemp oils, are increasingly used to support the ECS tone, promote healthy metabolism, improve risk factors associated with cardiovascular disorders, encourage brain health and emotional well-being, and ameliorate inflammation. While hemp cannabinoids of THC and CBD groups show distinct but complementary actions through a variety of cannabinoid (CB1 and CB2), adenosine (A2A), and vanilloid (TRPV1) receptors, they also modulate PUFA metabolism within a wide variety of specialized lipid mediators that promote or resolve inflammation and oxidative stress. Clinical evidence reviewed in this study links PUFAs and cannabinoids to changes in ECS tone, immune function, metabolic and oxidative stress adaptation, and overall maintenance of a well-balanced systemic function of the body. Understanding how the body coordinates signals from the exogenous and endogenous ECS modulators is critical for discerning the underlying molecular mechanisms of the ECS tone in healthy and disease states. Nutritional and lifestyle interventions represent promising approaches to address chronic metabolic and inflammatory disorders that may overlap in the population at risk. Further investigation and validation of dietary interventions that modulate the ECS are required in order to devise clinically successful second-generation management strategies.


2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Bo Liang ◽  
Yong-Chun Zhu ◽  
Jia Lu ◽  
Ning Gu

The oxidative stress reaction is the imbalance between oxidation and antioxidation in the body, resulting in excessive production of oxygen free radicals in the body that cannot be removed, leading to excessive oxidation of the body, and causing damage to cells and tissues. A large number of studies have shown that oxidative stress is involved in the pathological process of many diseases, so inhibiting oxidative stress, that is, antioxidation, is of great significance for the treatment of diseases. Studies have shown that many traditional Chinese medications contain antioxidant active bioactive compounds, but the mechanisms of those compounds are different and complicated. Therefore, by summarizing the literature on antioxidant activity of traditional Chinese medication-based bioactive compounds in recent years, our review systematically elaborates the main antioxidant bioactive compounds contained in traditional Chinese medication and their mechanisms, so as to provide references for the subsequent research.


2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Visweswara Rao Pasupuleti ◽  
Chandra Sekhar Arigela ◽  
Siew Hua Gan ◽  
Sirajudeen Kuttulebbai Nainamohamed Salam ◽  
Kumara Thevan Krishnan ◽  
...  

Despite the availability of various antidiabetic drugs, diabetes mellitus (DM) remains one of the world’s most prevalent chronic diseases and is a global burden. Hyperglycaemia, a characteristic of type 2 diabetes mellitus (T2DM), substantially leads to the generation of reactive oxygen species (ROS), triggering oxidative stress as well as numerous cellular and molecular modifications such as mitochondrial dysfunction affecting normal physiological functions in the body. In mitochondrial-mediated processes, oxidative pathways play an important role, although the responsible molecular mechanisms remain unclear. The impaired mitochondrial function is evidenced by insulin insensitivity in various cell types. In addition, the roles of master antioxidant pathway nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1)/antioxidant response elements (ARE) are being deciphered to explain various molecular pathways involved in diabetes. Dietary factors are known to influence diabetes, and many natural dietary factors have been studied to improve diabetes. Honey is primarily rich in carbohydrates and is also abundant in flavonoids and phenolic acids; thus, it is a promising therapeutic antioxidant for various disorders. Various research has indicated that honey has strong wound-healing properties and has antibacterial, anti-inflammatory, antifungal, and antiviral effects; thus, it is a promising antidiabetic agent. The potential antidiabetic mechanisms of honey were proposed based on its major constituents. This review focuses on the various prospects of using honey as an antidiabetic agent and the potential insights.


2020 ◽  
Vol 99 (5) ◽  
pp. 504-508
Author(s):  
Natalija A. Egorova ◽  
N. V. Kanatnikova

Iron is an assential element for the growth, division, differentiation and functioning of any cell in the body. Iron is virtually important for human and danger at the same time, because with excessive accumulation it causes oxidative stress with formation of highly active oxygen radicals and reactive form of nitrogen that can destroy cell membranes, proteins, nucleic acids, reduce cell viability, with, according to modern concepts, can contribute to the development of many diseases (cardiovascular, rheumatic, gastrointestinal, neurodegenerative, oncological, metabolic and others), and also accelerate the aging process. Part 1 of this review discussed the issues of iron metabolism in human, including its regulation at the cellular and systemic levels, the intake, transport, use, accumulation and export of iron in cells, the role of the labile iron pool in the cytoplasm of cells and plasma non-transferrin bound iron. Data are provided on the causes, frequency and significance of iron overload in the formation of free radicals and the development of oxidative stress. Part 2 of the review provides information on diseases associated with iron overload as well as information on ferroptosis - a new type of iron-dependent regulated cell death. Attention is paid to the works of domestic authors, where it was found that prolonged use of drinking water with a high iron content is unfavorable for the population and leads to an increase in the overall incidence, the development of the diseases of the blood, skin and subcutaneous tissue, musculoskeletal system, digestive system, urogenital system, and allergic diseases. Separate publications are cited on the possibility of a negative effect of iron at concentrations in water of 0.3 mg/l and lower. The material of the review emphasizes the preventive significance of caution attitude to regulating iron in the water in the Russian Federation, where 1/3 of the population uses iron-containing water for drinking, and substantiate the feasibility of establishing a hygienic limit for iron in water not higher than 0.3 mg/l.


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