-
Scientific Reports Oct 2022Berberine (BBR) is an isoquinoline alkaloid with several clinical therapeutic applications. Its low water solubility, absorption, and cellular bioavailability diminish...
Berberine (BBR) is an isoquinoline alkaloid with several clinical therapeutic applications. Its low water solubility, absorption, and cellular bioavailability diminish BBR's therapeutic efficacy. In this study, BBR was encapsulated into bovine serum albumin nanoparticles (BSA NPs) core to reduce BBR limitations and enhance its clinical therapeutic properties. Several physicochemical characterization tools, such as Dynamic Light Scattering and Ultraviolet-Visible spectroscopic measurements, field emission transmission electron microscopy surface morphology, Fourier transforms infrared spectroscopy, thermal stability analysis, and releasing studies, were used to evaluate the BBR-BSA NPs. Compared to BBR, BBR-BSA nanoparticles demonstrated superior free radical scavenging and antioxidant capacities, anti-hemolytic and anticoagulant efficacies, and antimicrobial activities, as demonstrated by the findings of the in vitro studies. Furthermore, a stressed pancreatic rat model was induced using a high-fat, high-sucrose diet plus carbon tetrachloride injection. The in vivo results revealed that BBR-BSA NPs substantially restored peripheral glucose metabolism and insulin sensitivity. Oral administration of BBR-BSA NPs also improved pancreatic β-cells homeostasis, upregulated pancreatic antioxidant mechanisms, inhibited oxidants generation, and attenuated oxidative injury in the stressed pancreatic tissues. In conclusion, our in vitro and in vivo results confirmed that BBR-BSA NPs demonstrated more potent antioxidant properties and restored pancreatic homeostasis compared to BBR.
Topics: Animals; Rats; Berberine; Serum Albumin, Bovine; Antioxidants; Carbon Tetrachloride; Nanoparticles; Glucose; Water; Isoquinolines; Sucrose; Oxidants; Anticoagulants; Anti-Infective Agents; Free Radicals
PubMed: 36261663
DOI: 10.1038/s41598-022-21568-8 -
Journal of Atherosclerosis and... Jun 2022Atherosclerosis is responsible for high morbidity and mortality rates around the world. Local arterial oxidative stress is involved in all phases of atherosclerosis...
AIM
Atherosclerosis is responsible for high morbidity and mortality rates around the world. Local arterial oxidative stress is involved in all phases of atherosclerosis development. Mitochondria is a relevant source of the oxidants, particularly under certain risky conditions, such as hypercholesterolemia. The aim of this study was to test whether lowering the production of mitochondrial oxidants by induction of a mild uncoupling can reduce atherosclerosis in hypercholesterolemic LDL receptor knockout mice.
METHODS
The mice were chronically treated with very low doses of DNP (2,4-dinitrophenol) and metabolic, inflammatory and redox state markers and atherosclerotic lesion sizes were determined.
RESULTS
The DNP treatment did not change the classical atherosclerotic risk markers, such as plasma lipids, glucose homeostasis, and fat mass, as well as systemic inflammatory markers. However, the DNP treatment diminished the production of mitochondrial oxidants, systemic and tissue oxidative damage markers, peritoneal macrophages and aortic rings oxidants generation. Most importantly, development of spontaneous and diet-induced atherosclerosis (lipid and macrophage content) were significantly decreased in the DNP-treated mice. In vitro, DNP treated peritoneal macrophages showed decreased HO production, increased anti-inflammatory cytokines gene expression and secretion, increased phagocytic activity, and decreased LDL-cholesterol uptake.
CONCLUSIONS
These findings are a proof of concept that activation of mild mitochondrial uncoupling is sufficient to delay the development of atherosclerosis under the conditions of hypercholesterolemia and oxidative stress. These results promote future approaches targeting mitochondria for the prevention or treatment of atherosclerosis.
Topics: Animals; Atherosclerosis; Humans; Hydrogen Peroxide; Hypercholesterolemia; Mice; Mice, Knockout; Mitochondria; Oxidants
PubMed: 34092712
DOI: 10.5551/jat.62796 -
Medicina (Kaunas, Lithuania) Dec 2021: Hypertrophic cardiomyopathy (HCM) depends on the primary impairment of sarcomeres, but it can also be associated with secondary alterations in the heart related to...
: Hypertrophic cardiomyopathy (HCM) depends on the primary impairment of sarcomeres, but it can also be associated with secondary alterations in the heart related to oxidative stress. The present study aimed to examine oxidative-antioxidant disturbances in patients with HCM compared with control individuals. : We enrolled 52 consecutive HCM patients and 97 controls without HCM. The groups were matched for age, body mass index, and sex. Peripheral blood was collected from all patients to determine the total antioxidant capacity (TAC), total oxidant status (TOS), lipid hydroperoxide (LPH), and malondialdehyde (MDA). The oxidative stress index (OSI) was defined as the ratio of the TOS level to the TAC level. : The median age was 52 years, and 58.4% were female. The area under the curve (AUC) indicated good predictive power for the TAC and TOS [AUC 0.77 (0.69-0.84) and 0.83 (0.76-0.90), respectively], as well as excellent predictive power for the OSI [AUC 0.87 (0.81-0.93)] for HCM detection. Lipid peroxidation markers also demonstrated good predictive power to detect HCM patients [AUC = 0.73, AUC = 0.79]. : The TOS, the TAC, LPH levels, and MDA levels have good predictive power for HCM detection. The holistic assessment of oxidative stress by the OSI had excellent power and could identify patients with HCM.
Topics: Antioxidants; Cardiomyopathy, Hypertrophic; Female; Humans; Malondialdehyde; Middle Aged; Oxidants; Oxidative Stress
PubMed: 35056338
DOI: 10.3390/medicina58010031 -
Archives of Biochemistry and Biophysics Sep 2022Humans have widespread exposure to both oxidants, and soft electrophilic compounds such as alpha,beta-unsaturated aldehydes and quinones. Electrophilic motifs are... (Review)
Review
Humans have widespread exposure to both oxidants, and soft electrophilic compounds such as alpha,beta-unsaturated aldehydes and quinones. Electrophilic motifs are commonly found in a drugs, industrial chemicals, pollutants and are also generated via oxidant-mediated degradation of biomolecules including lipids (e.g. formation of 4-hydroxynonenal, 4-hydroxyhexenal, prostaglandin J2). All of these classes of compounds react efficiently with Cys residues, and the particularly the thiolate anion, with this resulting in Cys modification via either oxidation or adduct formation. This can result in deleterious or beneficial effects, that are either reversible (e.g. in cell signalling) or irreversible (damaging). For example, acrolein is a well-established toxin, whereas dimethylfumarate is used in the treatment of multiple sclerosis and psoriasis. This short review discusses the targets of alpha,beta-unsaturated aldehydes, and particularly two prototypic cases, acrolein and dimethylfumarate, and the factors that control the selectivity and kinetics of reaction of these species. Comparison is made between the reactivity of oxidants versus soft electrophiles. These rate constants indicate that electrophiles can be significant thiol modifying agents in some situations, as they have rate constants similar to or greater than species such as HO, can be present at higher concentrations, and are less efficiently removed by protective systems when compared to HO. They may also induce similar or higher levels of modification than highly reactive oxidants, due to the very low concentrations of oxidants formed in most in vivo situations.
Topics: Acrolein; Aldehydes; Cysteine; Dimethyl Fumarate; Humans; Hydrogen Peroxide; Kinetics; Oxidants
PubMed: 35777524
DOI: 10.1016/j.abb.2022.109344 -
European Review For Medical and... Sep 2019Critical illnesses are a significant public health issue because of their high rate of mortality, the increasing use of the Intensive Care Units and the resulting... (Review)
Review
OBJECTIVE
Critical illnesses are a significant public health issue because of their high rate of mortality, the increasing use of the Intensive Care Units and the resulting healthcare cost that is about 80 billion of dollars per year. Their mortality is about 12% whereas sepsis mortality reaches 30-40%. The only instruments currently used against sepsis are early diagnosis and antibiotic therapies, but the mortality rate can also be decreased through an improvement of the patient's nutrition. The aim of this paper is to summarize the effects of vitamins A, B, C and E on the balance between pro-oxidants and anti-oxidants in the critical care setting to confirm "a beneficial care enhancing".
MATERIALS AND METHODS
The peer-reviewed articles analyzed were selected from PubMed databases using the keywords "critical care", "intensive care", "critical illness", "sepsis", "nutritional deficiency", "vitamins", "oxidative stress", "infection", and "surgery". Among the 654 papers identified, 160 articles were selected after title and abstract examination, removal of duplicates and of the studies on pediatric population. Finally, only the 92 articles relating to vitamins A, C, E and the B complex were analyzed.
RESULTS
The use of vitamins decreased morbidity and mortality in perioperative period and critically ill patients, especially in ICU. Among the most encouraging results, we found that the use of vitamins, both as monotherapy and in vitamins combinations, play a crucial role in the redox balance. Vitamins, especially vitamins A, C, E and the B complex, could help prevent oxidative damage through the breakdown of the oxidizing chemical chain reaction.
CONCLUSIONS
Even if the results of the studies are sometimes discordant or inconclusive, the current opinion is that the supplementation of one or more of these vitamins in critically ill patients may improve their clinical outcome, positively affecting the morbidity and the mortality. Further, randomized studies are required to deeply understand the potentiality of a vitamin supplementation therapy and develop homogeneous and standardized protocols to be adopted in every critical care scenario.
Topics: Critical Care; Critical Illness; Databases, Factual; Dietary Supplements; Humans; Oxidants; Oxidative Stress; Oxidoreductases; Treatment Outcome; Vitamins
PubMed: 31539163
DOI: 10.26355/eurrev_201909_18894 -
Journal of Thrombosis and Haemostasis :... Aug 2023Oxidative stress contributes to thrombosis in atherosclerosis, inflammation, infection, aging, and malignancy. Oxidant-induced cysteine modifications, including...
BACKGROUND
Oxidative stress contributes to thrombosis in atherosclerosis, inflammation, infection, aging, and malignancy. Oxidant-induced cysteine modifications, including sulfenylation, can act as a redox-sensitive switch that controls protein function. Protein disulfide isomerase (PDI) is a prothrombotic enzyme with exquisitely redox-sensitive active-site cysteines.
OBJECTIVES
We hypothesized that PDI is sulfenylated during oxidative stress, contributing to the prothrombotic potential of PDI.
METHODS
Biochemical and enzymatic assays using purified proteins, platelet and endothelial cell assays, and in vivo murine thrombosis studies were used to evaluate the role of oxidative stress in PDI sulfenylation and prothrombotic activity.
RESULTS
PDI exposure to oxidants resulted in the loss of PDI reductase activity and simultaneously promoted sulfenylated PDI generation. Following exposure to oxidants, sulfenylated PDI spontaneously converted to disulfided PDI. PDI oxidized in this manner was able to transfer disulfides to protein substrates. Inhibition of sulfenylation impaired disulfide formation by oxidants, indicating that sulfenylation is an intermediate during PDI oxidation. Agonist-induced activation of platelets and endothelium resulted in the release of sulfenylated PDI. PDI was also sulfenylated by oxidized low-density lipoprotein (oxLDL). In an in vivo model of thrombus formation, oxLDL markedly promoted platelet accumulation following an arteriolar injury. PDI oxidoreductase inhibition blocked oxLDL-mediated augmentation of thrombosis.
CONCLUSION
PDI sulfenylation is a critical posttranslational modification that is an intermediate during disulfide PDI formation in the setting of oxidative stress. Oxidants generated by vascular cells during activation promote PDI sulfenylation, and interference with PDI during oxidative stress impairs thrombus formation.
Topics: Animals; Mice; Cysteine; Disulfides; Oxidants; Oxidative Stress; Oxidoreductases; Protein Disulfide-Isomerases; Thrombosis
PubMed: 37037379
DOI: 10.1016/j.jtha.2023.03.034 -
International Immunopharmacology Jul 2021An increasing amount of reports in the literature is showing that medical ozone (O) is used, with encouraging results, in treating COVID-19 patients, optimizing pain and... (Review)
Review
An increasing amount of reports in the literature is showing that medical ozone (O) is used, with encouraging results, in treating COVID-19 patients, optimizing pain and symptoms relief, respiratory parameters, inflammatory and coagulation markers and the overall health status, so reducing significantly how much time patients underwent hospitalization and intensive care. To date, aside from mechanisms taking into account the ability of O to activate a rapid oxidative stress response, by up-regulating antioxidant and scavenging enzymes, no sound hypothesis was addressed to attempt a synopsis of how O should act on COVID-19. The knowledge on how O works on inflammation and thrombosis mechanisms is of the utmost importance to make physicians endowed with new guns against SARS-CoV2 pandemic. This review tries to address this issue, so to expand the debate in the scientific community.
Topics: Humans; Oxidants, Photochemical; Oxidative Stress; Ozone; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34020394
DOI: 10.1016/j.intimp.2021.107777 -
Current Opinion in Immunology Oct 2019The phagocyte NADPH oxidase possesses a transmembrane electron transferase comprised of gp91phox (aka NOX2) and p22phox and two multicomponent cytosolic complexes, which... (Review)
Review
The phagocyte NADPH oxidase possesses a transmembrane electron transferase comprised of gp91phox (aka NOX2) and p22phox and two multicomponent cytosolic complexes, which in stimulated phagocytes translocate to assemble a functional enzyme complex at plasma or phagosomal membranes. The NOX2-centered NADPH oxidase shuttles electrons from cytoplasmic NADPH to molecular oxygen in phagosomes or the extracellular space to produce oxidants that support optimal antimicrobial activity by phagocytes. Additionally, NOX2-generated oxidants have been implicated in both autocrine and paracrine signaling in a variety of biological contexts. However, when interpreting experimental results, investigators must recognize the complexity inherent in the biochemistry of oxidant-mediated attack of microbial targets and the technical limitations of the probes currently used to detect intracellular oxidants.
Topics: Animals; Granulomatous Disease, Chronic; Humans; Hydrogen Peroxide; NADPH Oxidase 2; Neutrophils; Oxidants; Oxidation-Reduction; Phagocytes; Phagocytosis; Phagosomes; Signal Transduction
PubMed: 31302569
DOI: 10.1016/j.coi.2019.05.006 -
International Journal of Molecular... Mar 2023The role of oxidative stress (OS) in male infertility as a primary etiology and/or concomitant cause in other situations, such as inflammation, varicocele and... (Review)
Review
The role of oxidative stress (OS) in male infertility as a primary etiology and/or concomitant cause in other situations, such as inflammation, varicocele and gonadotoxin effects, is well documented. While reactive oxygen species (ROS) are implicated in many important roles, from spermatogenesis to fertilization, epigenetic mechanisms which are transmissible to offspring have also recently been described. The present review is focused on the dual aspects of ROS, which are regulated by a delicate equilibrium with antioxidants due to the special frailty of spermatozoa, in continuum from physiological condition to OS. When the ROS production is excessive, OS ensues and is amplified by a chain of events leading to damage of lipids, proteins and DNA, ultimately causing infertility and/or precocious pregnancy termination. After a description of positive ROS actions and of vulnerability of spermatozoa due to specific maturative and structural characteristics, we linger on the total antioxidant capacity (TAC) of seminal plasma, which is a measure of non-enzymatic non-proteic antioxidants, due to its importance as a biomarker of the redox status of semen; the therapeutic implications of these mechanism play a key role in the personalized approach to male infertility.
Topics: Female; Male; Humans; Pregnancy; Reactive Oxygen Species; Oxidants; Antioxidants; Fertility; Oxidative Stress; Infertility, Male; Spermatozoa; Semen
PubMed: 36902424
DOI: 10.3390/ijms24054994 -
Molecular mechanisms in cognitive frailty: potential therapeutic targets for oxygen-ozone treatment.Mechanisms of Ageing and Development Mar 2020In the last decade, cognitive frailty has gained great attention from the scientific community. It is characterized by high inflammation and oxidant state, endocrine and... (Review)
Review
In the last decade, cognitive frailty has gained great attention from the scientific community. It is characterized by high inflammation and oxidant state, endocrine and metabolic alterations, mitochondria dysfunctions and slowdown in regenerative processes and immune system, with a complex and multifactorial aetiology. Although several treatments are available, challenges regarding the efficacy and the costs persist. Here, we proposed an alternative non-pharmacological, non-side-effect, low cost therapy based on anti-inflammation, antioxidant, regenerative and anti-pathogens properties of ozone, through the activation of several molecular mechanisms (Nrf2-ARE, NF-κB, NFAT, AP-1, HIFα). We highlighted how these specific processes could be implicated in cognitive frailty to identify putative therapeutic targets for its treatment. The oxigen-ozone (O-O) therapy has never been tested for cognitive frailty. This work provides thus wide scientific background to build a consistent rationale for testing for the first time this therapy, that could modulate the immune, inflammatory, oxidant, metabolic, endocrine, microbiota and regenerative processes impaired in cognitive frailty. Although insights are needed, the O-O therapy could represent a faster, easier, inexpensive monodomain intervention working in absence of side effects for cognitive frailty.
Topics: Cellular Senescence; Cognitive Aging; Humans; Inflammation; Oxidants, Photochemical; Ozone
PubMed: 31982474
DOI: 10.1016/j.mad.2020.111210