scholarly journals Oxidative Stress as a Possible Target in the Treatment of Toxoplasmosis: Perspectives and Ambiguities

2021 ◽  
Vol 22 (11) ◽  
pp. 5705
Author(s):  
Karolina Szewczyk-Golec ◽  
Marta Pawłowska ◽  
Roland Wesołowski ◽  
Marcin Wróblewski ◽  
Celestyna Mila-Kierzenkowska

Toxoplasma gondii is an apicomplexan parasite causing toxoplasmosis, a common disease, which is most typically asymptomatic. However, toxoplasmosis can be severe and even fatal in immunocompromised patients and fetuses. Available treatment options are limited, so there is a strong impetus to develop novel therapeutics. This review focuses on the role of oxidative stress in the pathophysiology and treatment of T. gondii infection. Chemical compounds that modify redox status can reduce the parasite viability and thus be potential anti-Toxoplasma drugs. On the other hand, oxidative stress caused by the activation of the inflammatory response may have some deleterious consequences in host cells. In this respect, the potential use of natural antioxidants is worth considering, including melatonin and some vitamins, as possible novel anti-Toxoplasma therapeutics. Results of in vitro and animal studies are promising. However, supplementation with some antioxidants was found to promote the increase in parasitemia, and the disease was then characterized by a milder course. Undoubtedly, research in this area may have a significant impact on the future prospects of toxoplasmosis therapy.

2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Iwona Zwolak

Vanadium (V) in its inorganic forms is a toxic metal and a potent environmental and occupational pollutant and has been reported to induce toxic effects in animals and people. In vivo and in vitro data show that high levels of reactive oxygen species are often implicated in vanadium deleterious effects. Since many dietary (exogenous) antioxidants are known to upregulate the intrinsic antioxidant system and ameliorate oxidative stress-related disorders, this review evaluates their effectiveness in the treatment of vanadium-induced toxicity. Collected data, mostly from animal studies, suggest that dietary antioxidants including ascorbic acid, vitamin E, polyphenols, phytosterols, and extracts from medicinal plants can bring a beneficial effect in vanadium toxicity. These findings show potential preventive effects of dietary antioxidants on vanadium-induced oxidative stress, DNA damage, neurotoxicity, testicular toxicity, and kidney damage. The relevant mechanistic insights of these events are discussed. In summary, the results of studies on the role of dietary antioxidants in vanadium toxicology appear encouraging enough to merit further investigations.


Microbiology ◽  
2009 ◽  
Vol 155 (5) ◽  
pp. 1451-1458 ◽  
Author(s):  
Beverley A. Bray ◽  
Iain C. Sutcliffe ◽  
Dean J. Harrington

Although Streptococcus agalactiae, the group B Streptococcus, is a leading cause of invasive neonatal disease worldwide the molecular basis of its virulence is still poorly understood. To investigate the role of lipoproteins in the physiology and interaction of this pathogen with host cells, we generated a mutant S. agalactiae strain (A909ΔLgt) deficient in the Lgt enzyme and thus unable to lipidate lipoprotein precursors (pro-lipoproteins). The loss of pro-lipoprotein lipidation did not affect the viability of S. agalactiae or its growth in several different media, including cation-depleted media. The processing of two well-characterized lipoproteins, but not a non-lipoprotein, was clearly shown to be aberrant in A909ΔLgt. The mutant strain was shown to be more sensitive to oxidative stress in vitro although the molecular basis of this increased sensitivity was not apparent. The inactivation of Lgt also resulted in changes to the bacterial cell envelope, as demonstrated by reduced retention of both the group B carbohydrate and the polysaccharide capsule and a statistically significant reduction (P=0.0079) in A909ΔLgt adherence to human endothelial cells of fetal origin. These data confirm that failure to process lipoproteins correctly has pleiotropic effects that may be of significance to S. agalactiae colonization and pathogenesis.


2020 ◽  
Vol 9 (3) ◽  
pp. 191-199 ◽  
Author(s):  
Fatemeh Jamshidi-kia ◽  
Joko Priyanto Wibowo ◽  
Mostafa Elachouri ◽  
Rohollah Masumi ◽  
Alizamen Salehifard-Jouneghani ◽  
...  

Free radicals are constructed by natural physiological activities in the human cells as well as in the environment. They may be produced as a result of diet, smoking, exercise, inflammation, exposure to sunlight, air pollutants, stress, alcohol and drugs. Imbalanced redox status may lead to cellular oxidative stress, which can damage the cells of the body, resulting in an incidence of various diseases. If the endogenous antioxidants do not stop the production of reactive metabolites, they will be needed to bring about a balance in redox status. Natural antioxidants, for example plants, play an important part in this context. This paper seeks to report the available evidence about oxidative stress and the application of plants as antioxidant agents to fight free radicals in the human body. For this purpose, to better understand oxidative stress, the principles of free radical production, the role of free radicals in diseases, antioxidant defense mechanisms, and the role of herbs and diet in oxidative stress are discussed.


Author(s):  
Giovanni Pagano ◽  
Carla Manfredi ◽  
Federico V. Pallardó ◽  
Alex Lyakhovich ◽  
Luca Tiano ◽  
...  

Abstract Background The mitochondrial cofactors α-lipoic acid (ALA), coenzyme Q10 (CoQ10) and carnitine (CARN) play distinct and complementary roles in mitochondrial functioning, along with strong antioxidant actions. Also termed mitochondrial nutrients (MNs), these cofactors have demonstrated specific protective actions in a number of chronic disorders, as assessed in a well-established body of literature. Methods Using PubMed, the authors searched for articles containing information on the utilization of MNs in inflammatory disorders as assessed from in vitro and animal studies, and in clinical trials, in terms of exerting anti-inflammatory actions. Results The retrieved literature provided evidence relating acute pathologic conditions, such as sepsis and pneumonia, with a number of redox endpoints of biological and clinical relevance. Among these findings, both ALA and CARN were effective in counteracting inflammation-associated redox biomarkers, while CoQ10 showed decreased levels in proinflammatory conditions. MN-associated antioxidant actions were applied in a number of acute disorders, mostly using one MN. The body of literature assessing the safety and the complementary roles of MNs taken together suggests an adjuvant role of MN combinations in counteracting oxidative stress in sepsis and other acute disorders, including COVID-19-associated pneumonia. Conclusions The present state of art in the use of individual MNs in acute disorders suggests planning adjuvant therapy trials utilizing MN combinations aimed at counteracting proinflammatory conditions, as in the case of pneumonia and the COVID-19 pandemic.


Author(s):  
Nazaret Peña-Gil ◽  
Cristina Santiso-Bellón ◽  
Roberto Gozalbo-Rovira ◽  
Javier Buesa ◽  
Vicente Monedero ◽  
...  

Rotavirus (RV) and norovirus (NoV) are the leading cause of acute gastroenteritis (AGE) worldwide. Several studies have demonstrated that histo-blood group antigens (HBGAs) have a role in NoV and RV infections, since their presence on the gut epithelial surfaces is essential for the susceptibility to many NoV and RV genotypes. Polymorphisms in genes that code for enzymes required for HBGAs synthesis lead to secretor or non-secretor and Lewis positive and Lewis negative individuals. While secretor individuals appear to be more susceptible to RV infections, regarding NoVs infections there are too many discrepancies that prevent drawing conclusions. A second factor that influences enteric viral infections is the gut microbiota of the host. In vitro and animal studies have determined that the gut microbiota limits, but in some cases enhances, enteric viral infection. The ways microbiota can enhance NoV or RV infection include virion stabilization and promotion of virus attachment to host cells, whereas experiments with microbiota-depleted and germ-free animals point to immunoregulation as the mechanism by which the microbiota restricts infection. Human trials with live, attenuated RV vaccines and analysis of the microbiota in responders and non-responders individuals also allowed the identification of bacterial taxa linked to vaccine efficacy. As more information is gained on the complex relationships that are established between the host (glycobiology and immune system), the gut microbiota and the intestinal viruses, new avenues will be open for the development of novel anti-NoV and anti-RV therapies.


2021 ◽  
Vol 22 (24) ◽  
pp. 13473
Author(s):  
Nazaret Peña-Gil ◽  
Cristina Santiso-Bellón ◽  
Roberto Gozalbo-Rovira ◽  
Javier Buesa ◽  
Vicente Monedero ◽  
...  

Rotavirus (RV) and norovirus (NoV) are the leading causes of acute gastroenteritis (AGE) worldwide. Several studies have demonstrated that histo-blood group antigens (HBGAs) have a role in NoV and RV infections since their presence on the gut epithelial surfaces is essential for the susceptibility to many NoV and RV genotypes. Polymorphisms in genes that code for enzymes required for HBGAs synthesis lead to secretor or non-secretor and Lewis positive or Lewis negative individuals. While secretor individuals appear to be more susceptible to RV infections, regarding NoVs infections, there are too many discrepancies that prevent the ability to draw conclusions. A second factor that influences enteric viral infections is the gut microbiota of the host. In vitro and animal studies have determined that the gut microbiota limits, but in some cases enhances enteric viral infection. The ways that microbiota can enhance NoV or RV infection include virion stabilization and promotion of virus attachment to host cells, whereas experiments with microbiota-depleted and germ-free animals point to immunoregulation as the mechanism by which the microbiota restrict infection. Human trials with live, attenuated RV vaccines and analysis of the microbiota in responder and non-responder individuals also allowed the identification of bacterial taxa linked to vaccine efficacy. As more information is gained on the complex relationships that are established between the host (glycobiology and immune system), the gut microbiota and intestinal viruses, new avenues will open for the development of novel anti-NoV and anti-RV therapies.


2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Nathalie Auberval ◽  
Stéphanie Dal ◽  
William Bietiger ◽  
Elodie Seyfritz ◽  
Jean Peluso ◽  
...  

Thein vitromethods currently used to screen bioactive compounds focus on the use of a single model of oxidative stress. However, this simplistic view may lead to conflicting results. The aim of this study was to evaluate the antioxidant properties of two natural extracts (a mix of red wine polyphenols (RWPs) and epigallocatechin gallate (EGCG)) with three models of oxidative stress induced with hydrogen peroxide (H2O2), a mixture of hypoxanthine and xanthine oxidase (HX/XO), or streptozotocin (STZ) in RINm5F beta cells. We employed multiple approaches to validate their potential as therapeutic treatment options, including cell viability, reactive oxygen species production, and antioxidant enzymes expression. All three oxidative stresses induced a decrease in cell viability and an increase in apoptosis, whereas the level of ROS production was variable depending on the type of stress. The highest level of ROS was found for the HX/XO-induced stress, an increase that was reflected by higher expression antioxidant enzymes. Further, both antioxidant compounds presented beneficial effects during oxidative stress, but EGCG appeared to be a more efficient antioxidant. These data indicate that the efficiency of natural antioxidants is dependent on both the nature of the compound and the type of oxidative stress generated.


2002 ◽  
Vol 30 (4) ◽  
pp. 755-758 ◽  
Author(s):  
J. L. Buss ◽  
J. Neuzil ◽  
P. Ponka

Pyridoxal isonicotinoyl hydrazone (PIH) analogues are effective iron chelators in vivo and in vitro, and may be of value for the treatment of secondary iron overload. The sensitivity of Jurkat cells to Fe-chelator complexes was enhanced several-fold by the depletion of the antioxidant glutathione, indicating the role of oxidative stress in their toxicity. K562 cells loaded with eicosapentaenoic acid, a fatty acid particularly susceptible to oxidation, were also more sensitive to the toxic effects of the Fe complexes, and toxicity was proportional to lipid peroxidation. Thus Fechelator complexes cause oxidative stress, which may be a major component of their toxicity. As was the case for their Fe complexes, the toxicity of PIH analogues was enhanced by glutathione depletion of Jurkat cells and eicosapentaenoic acidloading of K562 cells. Thus the toxicity of the chelators themselves is also enhanced by compromised cellular redox status. In addition, the toxicity of the chelators was diminished by culturing Jurkat cells under hypoxic conditions, which may limit the production of the reactive oxygen species that initiate oxidative stress. A significant part of the toxicity of the chelators may be due to intracellular formation of Fe-chelator complexes, which oxidatively destroy the cell.


Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 282
Author(s):  
Anamaria Jurcau

Dementia, and especially Alzheimer’s disease (AD), puts significant burden on global healthcare expenditure through its increasing prevalence. Research has convincingly demonstrated the implication of oxidative stress in the pathogenesis of dementia as well as of the conditions which increase the risk of developing dementia. However, drugs which target single pathways have so far failed in providing significant neuroprotection. Natural antioxidants, due to their effects in multiple pathways through which oxidative stress leads to neurodegeneration and triggers neuroinflammation, could prove valuable weapons in our fight against dementia. Although efficient in vitro and in animal models of AD, natural antioxidants in human trials have many drawbacks related to the limited bioavailability, unknown optimal dose, or proper timing of the treatment. Nonetheless, trials evaluating several of these natural compounds are ongoing, as are attempts to modify these compounds to achieve improved bioavailability.


Author(s):  
Lara Bittmann

On December 31, 2019, WHO was informed of cases of pneumonia of unknown cause in Wuhan City, China. A novel coronavirus was identified as the cause by Chinese authorities on January 7, 2020 and was provisionally named "2019-nCoV". This new Coronavirus causes a clinical picture which has received now the name COVID-19. The virus has spread subsequently worldwide and was explained on the 11th of March, 2020 by the World Health Organization to the pandemic.


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