RESUMEN

Benzoic acids, which are commonly found in food, are also produced by human microbiota from other dietary phenolics. The aim was to investigate the interactions of 8 food-related benzoic acids with the physiological metals iron and copper under different (patho)physiologically relevant pH conditions in terms of chelation, reduction, impact on the metal-based Fenton chemistry, and copper-based hemolysis. Only 3,4-dihydroxybenzoic acid behaved as a protective substance under all conditions. It chelated iron, reduced both iron and copper, and protected against the iron and copper-based Fenton reaction. Conversely, 2,4,6-trihydroxybenzoic acid did not chelate iron and copper, reduced both metals, potentiated the Fenton reaction, and worsened copper-based hemolysis of rat red blood cells. The other tested compounds showed variable effects on the Fenton reaction. Interestingly, prooxidative benzoic acids mildly protected human erythrocytes against Cu-induced lysis. In conclusion, 3,4-dihydroxybenzoic acid seems to have a protective effect against copper and iron-based toxicity under different conditions.

Asunto(s)

Benzoatos , Cobre , Eritrocitos , Hierro , Cobre/química , Hierro/química , Humanos , Ratas , Animales , Eritrocitos/efectos de los fármacos , Eritrocitos/química , Eritrocitos/metabolismo , Benzoatos/química , Hemólisis/efectos de los fármacos , Quelantes/química , Quelantes/farmacología

RESUMEN

Background: The antioxidant system in a preterm neonate is premature. The imbalance between the prooxidant and antioxidant systems can make these neonates prone to oxidative stress. Birth asphyxia is one of the factors that can disturb this balance. Objective: We studied the prooxidant-antioxidant balance (PAB) in the diagnosis and developmental prognosis of preterm neonates with asphyxia. Methods: This cohort study has been conducted between 2016 and 2022 with 2 years follow-up on 183 premature neonates admitted to Ghaem Hospital Mashhad, by using a convenience sampling method. The data-collection tool and the researcher-made checklist included the mothers' and the neonate's information, and the third segment included laboratory information. PAB was studied by using standard solutions and the Enzyme immunoassays (ELISA) method. After discharging the newborns from the hospital, they were under follow-up at 6 months, 12 months, 18 months, and 24 months, by using the Denver II test. PAB was compared among newborns with asphyxia, those without asphyxia, and also newborns with normal and abnormal outcomes in both groups. Results: The mean ± standard deviation of the PAB factor reported is as follows: in newborns without asphyxia (21.00 ± 18.14 HK), those with asphyxia (31.00 ± 45.42 HK), in newborns with asphyxia having abnormal outcomes (40.00 ± 60.84 HK), and those having normal outcomes (21.00 ± 18.67 HK) (P ≤ 0.05). PAB results >25 HK have been used for the diagnosis of asphyxia prognosis in newborns, with 83.3% sensitivity and 81% specificity. Conclusion: The PAB index showed a significant increase after asphyxia. It can be used as a diagnostic marker for the prognosis of premature newborns with asphyxia. Thus, diagnosis and prognosis of asphyxia in premature newborns can be predicted by using the PAB index.

RESUMEN

BACKGROUND: Existing studies have suggested a link between oxidative stress levels and depression. Additionally, factors such as gender and conditions like hypertension have been shown to influence oxidative stress. This ten-year follow-up cohort study aims to examine the association between prooxidant-antioxidant balance (PAB) and the onset of depression and its symptoms in both hypertensive and normotensive individuals, while considering gender differences. METHODS: The data for this study was obtained from the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) study, a cohort study conducted in eastern Iran. Serum PAB levels were measured in 1702 hypertensive and 4096 normotensive individuals aged 35 to 65 years. After ten years, the participants' depression status was evaluated using the Beck questionnaire, and depression symptoms were investigated using the BDI-II structural model, which includes somatic, affective, and cognitive symptoms. RESULT: The analysis indicates that in hypertensive male participants, the highest tertile of PAB is associated with an increased risk of depression (ß: 1.22, 95 % CI: -0.046, 2.485; P = 0.059) and symptoms of depression, including cognitive (ß: 2.937, 95 % CI: 0.511, 5.362; P = 0.018) and somatic (ß: 2.654, 95 % CI: 0.37, 4.939; P = 0.023) symptoms. However, there was no significant association between affective symptoms and PAB tertiles. Additionally, there was no significant link between depression and depressive symptoms in female hypertensive and normotensive individuals. CONCLUSION: In male hypertensive patients, but not in normotensive individuals of both genders and hypertensive women, depression and its associated symptoms, including somatic and cognitive symptoms, are associated with elevated levels of oxidative stress, as evidenced by higher serum PAB values. PAB is not associated with affective symptoms. Future studies should focus on the gender-specific nature of this relationship and work to clarify its underlying mechanisms.

RESUMEN

Cancer is a serious global health problem, causing the loss of millions of lives each year. Plumbagin, a compound derived from the medicinal plant Plumbago zeylanica, has shown promise in stopping the growth of tumor cells both in laboratory settings and in living organisms. Many plant-based compounds exert their effects through copper's ability to produce reactive oxygen species (ROS). This study aimed to understand how plumbagin, dependent on copper, induces cell death (apoptosis) in human cancer cells through various experiments. The results demonstrate that plumbagin hinders the growth of pancreatic cancer cells PNAC-1 and MIA PaCa-2 by utilizing the copper naturally present in the cells. Unlike metal chelators that remove iron and zinc (desferrioxamine mesylate and histidine), a specific copper chelator called neocuproine lessens the cell death caused by plumbagin. When ROS scavengers are used, plumbagin-induced apoptosis is inhibited, indicating that ROS plays a role in initiating cell death. The study also proves that plumbagin prevents copper from leaving cancer cells by suppressing the expression of specific genes (CTR1 and ATP7A). It is confirmed that plumbagin targets the nuclear copper, leading to signals that promote oxidative stress and, ultimately, cell death. These findings provide valuable insights into the potential of plumbagin as a substance to combat cancer, highlighting the importance of understanding how copper behaves within cancer cells.

Asunto(s)

Apoptosis , Proliferación Celular , Cobre , Naftoquinonas , Especies Reactivas de Oxígeno , Humanos , Naftoquinonas/farmacología , Naftoquinonas/química , Cobre/química , Cobre/farmacología , Línea Celular Tumoral , Especies Reactivas de Oxígeno/metabolismo , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Quelantes/farmacología , Quelantes/química , Fenantrolinas/química , Fenantrolinas/farmacología , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos/farmacología , Antineoplásicos/química

RESUMEN

Conventional cancer therapy strategies, although centered around killing tumor cells, often lead to severe side effects on surrounding normal tissues, thus compromising the chronic quality of life in cancer survivors. Hydrogen peroxide (H2O2) is a secondary signaling molecule that has an array of functions in both tumor and normal cells, including the promotion of cell survival pathways and immune cell modulation in the tumor microenvironment. H2O2 is a reactive oxygen species (ROS) crucial in cellular homeostasis and signaling (at concentrations maintained under nM levels), with increased steady-state levels in tumors relative to their normal tissue counterparts. Increased steady-state levels of H2O2 in tumor cells, make them vulnerable to oxidative stress and ultimately, cell death. Recently, H2O2-producing therapies-namely, pharmacological ascorbate and superoxide dismutase mimetics-have emerged as compelling complementary treatment strategies in cancer. Both pharmacological ascorbate and superoxide dismutase mimetics can generate excess H2O2 to overwhelm the impaired H2O2 removal capacity of cancer cells. This review presents an overview of H2O2 metabolism in the physiological and malignant states, in addition to discussing the anti-tumor and normal tissue-sparing mechanism(s) of, and clinical evidence for, two H2O2-based therapies, pharmacological ascorbate and superoxide dismutase mimetics.

Asunto(s)

Peróxido de Hidrógeno , Neoplasias , Humanos , Peróxido de Hidrógeno/metabolismo , Neoplasias/metabolismo , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Animales , Estrés Oxidativo/efectos de los fármacos , Microambiente Tumoral , Ácido Ascórbico/farmacología , Ácido Ascórbico/uso terapéutico , Ácido Ascórbico/metabolismo , Superóxido Dismutasa/metabolismo , Especies Reactivas de Oxígeno/metabolismo

RESUMEN

Background and Objectives: In this study, we aimed to investigate the effects of bosentan, an endothelin receptor antagonist, on endothelin-1 (ET-1), hypoxia-inducible factor-1 (HIF-1), nuclear factor-kappa B (NF-κB), and tumor necrosis factor (TNF)-α as inflammation markers, pro-oxidant antioxidant balance (PAB), and total antioxidant capacity (TAC) levels as oxidative stress parameters in lung tissues of rats in an experimental model of pulmonary contusion (PC) induced by blunt thoracic trauma. Materials and Methods: Thirty-seven male Sprague-Dawley rats were divided into five groups. C: The control group (n = 6) consisted of unprocessed and untreated rats. PC3 (n = 8) underwent 3 days of PC. PC-B3 (n = 8) received 100 mg/kg bosentan and was given orally once a day for 3 days. The PC7 group (n = 7) underwent 7 days of PC, and PC-B7 (n = 8) received 100 mg/kg bosentan and was given orally once a day for 7 days. Results: ET-1, NF-κB, TNF-α, HIF-1α, and PAB levels were higher, while TAC activity was lower in all groups compared with the control (p < 0.05). There was no significant difference in ET-1 and TNF-α levels between the PC-B3 and PC-B7 groups and the control group (p < 0.05), while NF-κB, HIF-1α, and PAB levels were still higher in both the PC-B3 and PC-B7 groups than in the control group. Bosentan decreased ET-1, NF-κB, TNF-α, HIF-1α, and PAB and increased TAC levels in comparison to the nontreated groups (p < 0.05). Conclusions: Bosentan decreased the severity of oxidative stress in the lungs and reduced the inflammatory reaction in rats with PC induced by blunt thoracic trauma. This suggests that bosentan may have protective effects on lung injury mechanisms by reducing hypoxia, inflammation, and oxidative stress. If supported by similar studies, bosentan can be used in both pulmonary and emergency clinics to reduce ischemic complications, inflammation, and oxidative stress in some diseases that may be accompanied by ischemia.

Asunto(s)

Bosentán , Modelos Animales de Enfermedad , Inflamación , Estrés Oxidativo , Ratas Sprague-Dawley , Sulfonamidas , Traumatismos Torácicos , Heridas no Penetrantes , Animales , Bosentán/uso terapéutico , Bosentán/farmacología , Estrés Oxidativo/efectos de los fármacos , Masculino , Ratas , Traumatismos Torácicos/complicaciones , Traumatismos Torácicos/tratamiento farmacológico , Sulfonamidas/farmacología , Sulfonamidas/uso terapéutico , Inflamación/tratamiento farmacológico , Heridas no Penetrantes/complicaciones , Heridas no Penetrantes/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/análisis , Hipoxia/complicaciones , Hipoxia/tratamiento farmacológico , Hipoxia/metabolismo , FN-kappa B/metabolismo , Endotelina-1/análisis , Antagonistas de los Receptores de Endotelina/uso terapéutico , Antagonistas de los Receptores de Endotelina/farmacología

RESUMEN

Alzheimer's disease (AD) is a major neurodegenerative disorder impacting millions of people with cognitive impairment and affecting activities of daily living. The deposition of neurofibrillary tangles of hyperphosphorylated tau proteins and accumulation of amyloid-ß (Aß) are the main pathological characteristics of AD. However, the actual causal process of AD is not yet identified. Oxidative stress occurs prior to amyloid Aß plaque formation and tau phosphorylation in AD. The role of master antioxidant, glutathione, and metal ions (e.g., iron) in AD are the frontline area of AD research. Iron overload in specific brain regions in AD is associated with the rate of cognitive decline. We have presented the outcome from various interventional trials involving iron chelators intended to minimize the iron overload in AD. To date, however, no significant positive outcomes have been reported using iron chelators in AD and warrant further research.

Asunto(s)

Enfermedad de Alzheimer , Ensayos Clínicos como Asunto , Quelantes del Hierro , Humanos , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Quelantes del Hierro/uso terapéutico , Ensayos Clínicos como Asunto/métodos , Sobrecarga de Hierro/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos

RESUMEN

This article examines the role of uric acid (UA) in cognitive changes and neurodegeneration, focusing on its functions as an antioxidant and prooxidant. Research suggests that changes in serum UA levels may be associated with the development or delay of cognitive impairment, especially in the context of neurodegenerative diseases such as Alzheimer's disease. It was revealed that there is a relationship between the level of UA and the dynamics of cognitive functions, indicating the potential neuroprotective properties of UA. Particular attention is paid to the balance between the antioxidant and prooxidant properties of UA, which may play a key role in protecting neurons from damage. However, research results are not clear-cut, highlighting the need for further research to more fully understand the role of UA in cognitive processes. Determining the optimal serum UA level may be an important step in developing strategies for the prevention and treatment of cognitive impairment associated with neurodegeneration. Overall, these studies advance the understanding of the mechanisms underlying the interaction between uric acid metabolism and brain health.

Asunto(s)

Enfermedades Neurodegenerativas , Ácido Úrico , Humanos , Ácido Úrico/sangre , Ácido Úrico/metabolismo , Enfermedades Neurodegenerativas/fisiopatología , Enfermedades Neurodegenerativas/metabolismo , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/prevención & control , Trastornos del Conocimiento/fisiopatología , Antioxidantes , Enfermedad de Alzheimer/fisiopatología , Enfermedad de Alzheimer/metabolismo , Encéfalo/metabolismo , Encéfalo/fisiopatología , Estrés Oxidativo/fisiología

RESUMEN

The present work deals with the sol-gel synthesis of silica-poly (vinylpyrrolidone) hybrid materials. The nanohybrids (Si-PVP) have been prepared using an acidic catalyst at ambient temperature. Tetramethyl ortosilane (TMOS) was used as a silica precursor. Poly (vinylpyrrolidone) (PVP) was introduced into the reaction mixture as a solution in ethanol with a concentration of 20%. The XRD established that the as-prepared material is amorphous. The IR and 29Si MAS NMR spectra proved the formation of a polymerized silica network as well as the hydrogen bonding interactions between the silica matrix and OH hydrogens of the silanol groups. The TEM showed spherical particle formation along with increased agglomeration tendency. The efficacy of SiO2/PVP nanoparticles as a potential antimicrobial agent against a wide range of bacteria was evaluated as bacteriostatic, using agar diffusion and spot tests. Combined effects of hybrid nanomaterial and antibiotics could significantly reduce the bactericidal concentrations of both the antibiotic and the particles, and they could also eliminate the antibiotic resistance of the pathogen. The registered prooxidant activity of the newly synthesized material was confirmative and explicatory for the antibacterial properties of the tested substance and its synergetic combination with antibiotics. The effect of new hybrid material on Crustacea Daphnia magna was also estimated as harmless under concentration of 0.1 mg/mL.

Asunto(s)

Antibacterianos , Povidona , Dióxido de Silicio , Dióxido de Silicio/química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Povidona/química , Pruebas de Sensibilidad Microbiana , Nanopartículas/química , Transición de Fase , Bacterias/efectos de los fármacos

RESUMEN

This study aimed to explore the antioxidant and prooxidative activity of two natural furanocoumarin derivatives, Bergaptol (4-Hydroxy-7H-furo [3,2-g] [1]benzopyran-7-one, BER) and Xanthotoxol (9-Hydroxy-7H-furo [3,2-g] [1]benzopyran-7-one, XAN). The collected thermodynamic and kinetic data demonstrate that both compounds possess substantial antiradical activity against HO• and CCl3OO• radicals in physiological conditions. BER exhibited better antiradical activity in comparison to XAN, which can be attributed to the enhanced deprotonation caused by the positioning of the -OH group on the psoralen ring. In contrast to highly reactive radical species, newly formed radical species BER• and XAN• exhibited negligible reactivity towards the chosen constitutive elements of macromolecules (fatty acids, amino acids, nucleobases). Furthermore, in the presence of O2•─, the ability to regenerate newly formed radicals BER• and XAN• was observed. Conversely, in physiological conditions in the presence of Cu(II) ions, both compounds exhibit prooxidative activity. Nevertheless, the prooxidative activity of both compounds is less prominent than their antioxidant activity. Furthermore, it has been demonstrated that anionic species can engage in the creation of a chelate complex, which restricts the reduction of metal ions when reducing agents are present (O2•─ and Asc─). Moreover, studies have demonstrated that these chelating complexes can be coupled with other radical species, hence enhancing their ability to inactivate radicals. Both compounds exhibited substantial inhibitory effects against enzymes involved in the direct or indirect generation of ROS: Xanthine Oxidase (XOD), Lipoxygenase (LOX), Myeloperoxidase (MPO), NADPH oxidase (NOX).

Asunto(s)

Antioxidantes , Furocumarinas , Furocumarinas/química , Furocumarinas/farmacología , Cinética , Antioxidantes/química , Antioxidantes/farmacología , Teoría Funcional de la Densidad , Oxidación-Reducción , Termodinámica , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Lipooxigenasa/metabolismo , Xantina Oxidasa/metabolismo , Xantina Oxidasa/antagonistas & inhibidores , Productos Biológicos/química , Productos Biológicos/farmacología , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/farmacología

RESUMEN

Autophagy is a degradation process that is evolutionarily conserved and is essential in maintaining cellular and physiological homeostasis through lysosomal removal and elimination of damaged peptides, proteins and cellular organelles. The dysregulation of autophagy is implicated in various diseases and disorders, including cancers, infection-related, and metabolic syndrome-related diseases. Propolis has been demonstrated in various studies including many human clinical trials to have antimicrobial, antioxidant, anti-inflammatory, immune-modulator, neuro-protective, and anti-cancer. Nevertheless, the autophagy modulation properties of propolis have not been extensively studied and explored. The role of propolis and its bioactive compounds in modulating cellular autophagy is possibly due to their dual role in redox balance and inflammation. The present review attempts to discuss the activities of propolis as an autophagy modulator in biological models in relation to various diseases/disorders which has implications in the development of propolis-based nutraceuticals, functional foods, and complementary therapies.

Asunto(s)

Autofagia , Inflamación , Oxidación-Reducción , Própolis , Própolis/farmacología , Humanos , Autofagia/efectos de los fármacos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/patología , Animales , Oxidación-Reducción/efectos de los fármacos , Antiinflamatorios/farmacología

RESUMEN

Their unique physicochemical properties and multi-enzymatic activity make CeO2 nanoparticles (CeO2 NPs) the most promising active component of the next generation of theranostic drugs. When doped with gadolinium ions, CeO2 NPs constitute a new type of contrast agent for magnetic resonance imaging, possessing improved biocatalytic properties and a high level of biocompatibility. The present study is focused on an in-depth analysis of the enzyme-like properties of gadolinium-doped CeO2 NPs (CeO2:Gd NPs) and their antioxidant activity against superoxide anion radicals, hydrogen peroxide, and alkylperoxyl radicals. Using an anion-exchange method, CeO2:Gd NPs (~5 nm) with various Gd-doping levels (10 mol.% or 20 mol.%) were synthesized. The radical-scavenging properties and biomimetic activities (namely SOD- and peroxidase-like activities) of CeO2:Gd NPs were assessed using a chemiluminescent method with selective chemical probes: luminol, lucigenin, and L-012 (a highly sensitive luminol analogue). In particular, gadolinium doping has been shown to enhance the radical-scavenging properties of CeO2 NPs. Unexpectedly, both bare CeO2 NPs and CeO2:Gd NPs did not exhibit SOD-like activity, acting as pro-oxidants and contributing to the generation of reactive oxygen species. Gadolinium doping caused an increase in the pro-oxidant properties of nanoscale CeO2. At the same time, CeO2:Gd NPs did not significantly inhibit the intrinsic activity of the natural enzyme superoxide dismutase, and CeO2:Gd NPs conjugated with SOD demonstrated SOD-like activity. In contrast to SOD-like properties, peroxidase-like activity was observed for both bare CeO2 NPs and CeO2:Gd NPs. This type of enzyme-like activity was found to be pH-dependent. In a neutral medium (pH = 7.4), nanoscale CeO2 acted as a prooxidant enzyme (peroxidase), while in an alkaline medium (pH = 8.6), it lost its catalytic properties; thus, it cannot be regarded as a nanozyme. Both gadolinium doping and conjugation with a natural enzyme were shown to modulate the interaction of CeO2 NPs with the key components of redox homeostasis.

RESUMEN

Resveratrol, a polyphenolic compound found primarily in red grapes and pomegranates is known as an antioxidant but can act as a pro-oxidant when copper ions are present. Here, resveratrol is demonstrated to reduce cell growth (as evaluated by MTT assay) and promote apoptosis-like cell death (as measured by Histone/DNA ELISA) in prostate cancer cell lines PC3 and C42B. This effect is effectively inhibited by a copper chelator (neocuproine) and reactive oxygen species (ROS) scavengers (thiourea for hydroxyl radical, superoxide dismutase for superoxide anion, and catalase for hydrogen peroxide). These inhibitory effects provide evidence that intracellular copper reacts with resveratrol within cancer cells, resulting in DNA damage via the generation of reactive oxygen species. Additionally, it has been demonstrated that non-tumorigenic epithelial cell lines (MCF-10A) grown in media supplemented with copper are more susceptible to growth inhibition by resveratrol, as confirmed by the observed reduction in cell proliferation. Copper supplementation induces enhanced expression of the copper transporter CTR1 in MCF-10A cells, which is reduced by the addition of resveratrol to the media. The selective cell death of cancer cells generated by copper-mediated and ROS mechanisms may help to explain the anticancer properties of resveratrol.

RESUMEN

Empirical studies have indicated that excessive tea consumption may potentially decrease folate levels within the human body. The main active component in green tea, epigallocatechin gallate (EGCG), significantly reduces the concentration of 5-methyltetrahydrofolate (5-MTHF) in both solution and serum. However, our findings also demonstrate that the pro-degradation effect of EGCG on 5-MTHF can be reversed by L-ascorbic acid (AA). Subsequent investigations suggest that EGCG could potentially expedite the degradation of 5-MTHF by generating hydrogen peroxide. In summary, excessive tea intake may lead to reduced folate levels in the bloodstream, yet timely supplementation of AA could potentially safeguard folate from degradation.

RESUMEN

The huge diversity of secondary bioactive metabolites, such as antibiotic and anticancer compounds produced by Micromonospora sp., makes it an attractive target for study. Here, we explored the anti-proliferative activities of Micromonospora sp. M2 extract (MBE) in relation to its pro-oxidative activities in A549 and MCF7 cell lines. Anti-proliferative effects were assessed by treating cells with MBE. We found that treatment with MBE decreased cell proliferation and increased intracellular reactive oxygen species, and that these observations were facilitated by the suppression of the PI3K-AKT pathway, alterations to the Bcl/Bad ratio, and increased caspase activity. These observations also demonstrated that MBE induced apoptotic cell death in cell lines. In addition, the phosphorylation of P38 and c-Jun N-terminal kinase (JNK) were upregulated following MBE treatment in both cell lines. Collectively, these results indicate that MBE acts as an anticancer agent via oxidative stress and JNK/mitogen-activated protein kinase pathway activation, enhancing apoptotic cell death in cell lines.

Asunto(s)

Apoptosis , Proliferación Celular , Micromonospora , Especies Reactivas de Oxígeno , Humanos , Células A549 , Células MCF-7 , Apoptosis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Proliferación Celular/efectos de los fármacos , Antineoplásicos/farmacología , Estrés Oxidativo/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/química

RESUMEN

CONTEXT: Herein, we compare and contrast the dual roles of Cun clusters (n = 3, 5, and 7 atoms) in scavenging or generating RO• free radicals from ROH at the theoretical levels (where R = H, methyl, ethyl, n-propyl, i-propyl, n-butyl, t-butyl, and phenyl). This investigation is performed in water media to mimic the actual environment in the biological system. In the presence of the Cun clusters, bond dissociation energy (BDE) of RO-H and R-OH is reduced. This is clear evidence for the increased possibility of both the RO-H and R-OH bonds breakage and scavenging of RO• radicals. The nature of anchoring bonds responsible for the interaction of Cun clusters with ROH and RO• are interpreted using the quantum theory of atoms in molecules (QTAIM) and the natural bond orbital (NBO) analysis. The DFT results indicate that the O•⋅⋅⋅•Cu bond is stronger and has more covalent character in RO•⋅⋅⋅•Cun radical complexes than in ROH⋅⋅⋅•Cun. Therefore, the interactions of Cun clusters with RO• radicals (antioxidant) are more pronounced than their interactions with ROH non-radicals (pro-oxidant). METHODS: The GAMESS software package was utilized in this paper. The B3LYP and M06 functions with the 6-311 + + G(d,p), and LANL2DZ/SDD basis sets was used to perform the important geometrical parameters of RO•⋅⋅⋅•Cun and ROH⋅⋅⋅•Cun, binding energy (Eb), and bond dissociation energy (BDE).

RESUMEN

Selenium (Se) is an essential trace element for humans and animals, but high-dose supplementation with Se compounds, most notably selenite, may exert cytotoxic and other adverse effects. On the other hand, bacteria, including Escherichia coli (E. coli), are capable of reducing selenite to red elemental Se that may serve as a safer Se source. Here, we examined how a diet of Se-enriched E. coli bacteria affected vital parameters and age-associated neurodegeneration in the model organism Caenorhabditis elegans (C. elegans). The growth of E. coli OP50 for 48 h in medium supplemented with 1 mM sodium selenite resulted in reddening of the bacterial culture, accompanied by Se accumulation in the bacteria. Compared to nematodes supplied with the standard E. coli OP50 diet, the worms fed on Se-enriched bacteria were smaller and slimmer, even though their food intake was not diminished. Nevertheless, given the choice, the nematodes preferred the standard diet. The fecundity of the worms was not affected by the Se-enriched bacteria, even though the production of progeny was somewhat delayed. The levels of the Se-binding protein SEMO-1, which serves as a Se buffer in C. elegans, were elevated in the group fed on Se-enriched bacteria. The occurrence of knots and ruptures within the axons of cholinergic neurons was lowered in aged nematodes provided with Se-enriched bacteria. In conclusion, C. elegans fed on Se-enriched E. coli showed less age-associated neurodegeneration, as compared to nematodes supplied with the standard diet.

RESUMEN

BACKGROUND: Treatment of Pancreatic Cancer (PC) is challenging due to its aggressiveness and acquired resistance to conventional chemotherapy and radiotherapy. Therefore, the discovery of new therapeutic agents and strategies is essential. Juglone, a naphthoquinone, is a secondary metabolite produced naturally in walnut-type trees having allelopathic features in its native environment. Juglone was shown to prevent cell proliferation and induce ROS-mediated mitochondrial apoptosis. Ascorbate with both antioxidant and oxidant features, shows selective cytotoxicity in cancer cells. METHODS AND RESULTS: In this study, we evaluated the anticancer effects of Juglone in combination with ascorbate in PANC-1 and BxPC-3 PC cells. The MTT assay was used to determine the IC50 dose of Juglone with 1 mM NaAscorbate (Jug-NaAsc). Subsequently, the cells were treated with 5, 10, 15 and 20 µM Jug-NaAsc for 24 h. Apoptotic effects were evaluated by analyzing the following genes using qPCR; proapoptotic Bax, antiapoptotic Bcl-2 related to the mitochondrial apoptotic pathway and apoptosis inhibitor Birc5 (Survivin). Immunofluorescence analysis was performed using Annexin V-FITC in PC cells. As an antioxidant enzyme, Trx2 protein levels were determined by a commercial ELISA test kit. Jug-NaAsc treatment decreased the expressions of antiapoptotic genes Bcl-2 and Birc5 while the apoptotic gene Bax expression increased at all doses. Additionally, a dose-dependently increase of apoptosis according to immunofluorescence analysis and the decreases of Trx2 enzyme levels at all treatments in both cell lines supported gene expression results. CONCLUSION: Our results suggest that Juglone is a potential anticancer agent especially when combined with ascorbate.

Asunto(s)

Naftoquinonas , Neoplasias Pancreáticas , Humanos , Especies Reactivas de Oxígeno/metabolismo , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Proteína X Asociada a bcl-2/metabolismo , Línea Celular Tumoral , Apoptosis , Ácido Ascórbico/farmacología , Naftoquinonas/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética

RESUMEN

Metabolic syndrome (MetS) is a symptomatic complex characterized by insulin resistance, impaired prooxidant-antioxidantbalance of the body with the development of subchronic inflammation, and dyslipidemia. The aim of the study is to investigate the effect of a complex pharmaceutical composition (CPC) (antioxidants and metabolitotropic agents), which is widely used in medical practice in Ukraine as a multivitamin complex, on experimental metabolic syndrome in rats. The effectof CPC on the correction of experimental MetS in rats, induced by a high content of carbohydrates and fats in the diet, was assessed. MetS in rats was characterized by a decrease in the sensitivity of cells to insulin, increased glucose content, and aviolation of its utilization, prooxidant-antioxidant disbalance. The results of the conducted studies indicate the positive effect of CPC, which contains ethyl esters of omega-3 acids, vitamin E, coenzyme Q10, zinc, vitamin A, biotin, and selenium, on the sensitivity of cells to insulin, glucose utilization, duration of hyperglycemia and indicators of free radical oxidation processes and antioxidant defense systems in rats with experimental MetS. These results prove the feasibility of using CPC to correct metabolic syndrome.

Asunto(s)

Resistencia a la Insulina , Síndrome Metabólico , Ratas , Animales , Síndrome Metabólico/tratamiento farmacológico , Antioxidantes/farmacología , Antioxidantes/metabolismo , Estrés Oxidativo , Insulina/metabolismo , Insulina/farmacología , Preparaciones Farmacéuticas , Glucosa

RESUMEN

Ascorbic acid (AsA) is an important nutrient for human health and disease cures, and it is also a crucial indicator for the quality of fruit and vegetables. As a reductant, AsA plays a pivotal role in maintaining the intracellular redox balance throughout all the stages of plant growth and development, fruit ripening, and abiotic stress responses. In recent years, the de novo synthesis and regulation at the transcriptional level and post-transcriptional level of AsA in plants have been studied relatively thoroughly. However, a comprehensive and systematic summary about AsA-involved biochemical pathways, as well as AsA's physiological functions in plants, is still lacking. In this review, we summarize and discuss the multiple physiological and biochemical functions of AsA in plants, including its involvement as a cofactor, substrate, antioxidant, and pro-oxidant. This review will help to facilitate a better understanding of the multiple functions of AsA in plant cells, as well as provide information on how to utilize AsA more efficiently by using modern molecular biology methods.

Asunto(s)

Antioxidantes , Ácido Ascórbico , Humanos , Ácido Ascórbico/metabolismo , Antioxidantes/metabolismo , Estrés Fisiológico , Frutas/metabolismo , Oxidación-Reducción , Regulación de la Expresión Génica de las Plantas