Free Radical Production Research Articles

The effect of DMSO on Saccharomyces cerevisiae yeast with different energy metabolism and antioxidant status

We studied the effect of dimethyl sulfoxide (DMSO) on the biochemical and physiological parameters of S. cerevisiae yeast cells with varied energy metabolism and antioxidant status. The wild-type cells of varied genetic backgrounds and their isogenic mutants with impaired antioxidant defences (Δsod mutants) or response to environmental stress (ESR) (Δmsn2, Δmsn4 and double Δmsn2msn4 mutants) were used. Short-term exposure to DMSO even at a wide range of concentrations (2–20%) had little effect on the metabolic activity of the yeast cells and the stability of their cell membranes, but induced free radicals production and clearly altered their proliferative activity. Cells of the Δsod1 mutant showed greater sensitivity to DMSO in these conditions. DMSO at concentrations from 4 to 10–14% (depending on the strain and genetic background) activated the ESR programme. The effects of long-term exposure to DMSO were mainly depended on the type of energy metabolism and antioxidant system efficiency. Yeast cells with reduced antioxidant system efficiency and/or aerobic respiration were more susceptible to the toxic effects of DMSO than cells with a wild-type phenotype and respiro-fermentative or fully fermentative metabolism. These studies suggest a key role of stress response programs in both the processes of cell adaptation to small doses of this xenobiotic and the processes related to its toxicity resulting from large doses or chronic exposure to DMSO.

Synergistic photocatalytic and antibacterial efficacies of Ag/rGO and Ag/Ag2O/rGO nanocomposites: The impact of oxide formation and ternary heterojunction

This study explores the efficient solvothermal integration of Ag/rGO and Ag/Ag2O/rGO nanocomposites using various solvents and employs thorough characterization procedures. The primary focus is on understanding the nuanced effects resulting from the combination of Ag nanoparticles with rGO nanosheets, particularly in the context of Ag2O formation. For a quantitative assessment of their photocatalytic and antibacterial properties, graphene oxide and silver nitrate (AgNO3) were introduced to create Ag/rGO and Ag/Ag2O/rGO nanocomposites. The results demonstrate a significant enhancement in photocatalytic performance for the Ag/Ag2O/rGO nanocomposite, achieving a rapid degradation of 99.99 % of methylene blue dye within 30 minutes under simulated solar light irradiation. This heightened efficiency is attributed to improved separation and transfer efficiency, as well as the substantial generation of photoinduced carriers due to the incorporation of visibly active Ag2O nanoparticles. Moreover, the Ag/Ag2O/rGO nanocomposite exhibits an enhanced antibacterial activity, reflected in Minimum Inhibitory Concentration (MIC) values of 50 μg/ml for Bacillus cereus and 300 μg/ml for Escherichia coli. The nanocomposite's higher antimicrobial activity against Gram-positive bacteria, particularly Bacillus cereus, is underscored, revealing its potential as an effective antibacterial agent. The formation of a ternary heterojunction in the Ag/Ag2O/rGO nanocomposite results in a notable increase in the production of free radicals, enhancing charge carrier migration and separation efficiency. This quantitative evidence emphasizes the versatile nature of the nanocomposite, highlighting its potential across diverse fields through augmented antibacterial and photocatalytic properties.

Computational study of the supramolecular complexation of azocompounds with cucurbit[7]uril: effects on the production and release of free radicals.

An inclusion complex between 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH), a widely employed azocompound, and cucurbit[7]util (CB[7]), has shown an increased yield of radicals derived from the homolytic cleavage of the azo bond. Aimed to get insights about the formation of complexes and their effect on the yield of radicals production, complexes of CB[7] with seven azocompounds were studied by computational methods. Molecular electrostatic surfaces and structural analysis showed that the inclusion of symmetrical azocompounds inside of CB[7] depends mainly on the charge density and position of the functional groups at the main chain of the azoderivative. Analysis of non-covalent interactions and thermodynamic outcomes revealed that positively charged azocompounds with amidinium or imidazolium groups presented strong favorable interactions (multiple hydrogen bonds) with the oxygens of CB[7] portals. Additionally, carbon-centered radicals generated from the complexes (azocompounds@CB[7]) were corroborated using the electron localization function (ELF). Results evidenced that the strength of the interactions and the level of inclusion (partial or complete) between the azocompound and CB[7] determined the final orientation of the radicals (located out- or inside of the CB[7] cavity). Obtained results could be employed to design new supramolecular systems based on the properties of azocomplound@CB[7] complexes for new scientific or industrial applications. First-principles calculations at B3LYP-D3BJ/6-311g(d,p) level theory in the gas phase and in solvent (PCM, water) were performed in Gaussian 16 software package. The dispersion energy correction was included through the Grimme's dispersion with Becke-Johnson damping D3(BJ). Thermodynamical data and the minimum character of all structures were obtained from vibrational frequency calculations. NBO, Multiwfn, Chemcraft, and NCIPLOT software were used to perform population analysis, analyze outcomes, visualize data, and display non-covalent interactions respectively.

PSVI-14 Effects of poor maternal nutrition during gestation on first generation offspring oxidative status in skeletal muscle

Abstract Poor maternal nutrition (restricted- and over-nutrition) during gestation negatively impacts offspring pre- and post-natal growth. Previous work has identified decreased muscle mass and increased adiposity, leading to poor quantity and quality of animal protein products. Alterations in oxidative status, such as the imbalance of antioxidant activity and the production of free radicals, can result in oxidative stress damaging lipid membranes, proteins, and DNA. Changes in oxidative status may contribute to the poor growth outcomes observed in offspring from poorly nourished dams. Therefore, the objective of this research was to determine the effects of poor maternal nutrition during gestation on the oxidative status in offspring skeletal muscle in sheep. We hypothesized that offspring of restricted- and over-fed ewes would have decreased antioxidant activity and increased products of oxidative stress in skeletal muscle. To test this hypothesis, multiparous Dorset ewes (n = 46) pregnant with twins were fed 100% (CON), 60% (RES), or 140% (OVER) of total nutrient requirements (NRC) from d 30 of gestation until parturition. Following parturition, ewes were fed a control diet throughout lactation. At d 282 of age semitendinosus (STN) samples were collected from rams at necropsy, and at d 284 of age muscle biopsies from STN were collected from ewes. Data were analyzed in SAS using PROC MIXED with fixed effects of maternal diet and offspring sex. Data were considered significant at P ≤ 0.05. The activity of the endogenous antioxidant superoxide dismutase (SOD) was decreased by 45% and 33% in RES and OVER offspring, respectively, compared with CON (P ≤ 0.01). Offspring sex did not alter STN SOD activity (P = 0.35). Muscle glutathione peroxidase (GPx) activity was decreased in RES offspring by 20% compared with CON (P ≤ 0.04), but neither differed from OVER offspring (P ≥ 0.24). Ewes had 34% greater GPx activity compared with rams (P < 0.0001). Offspring from RES and OVER ewes had 77% and 87% greater concentrations of malondialdehyde (MDA), a marker of lipid peroxidation, when compared with CON (P < 0.0001). Ewes had 29% greater MDA concentrations compared with rams (P = 0.05). Protein carbonyl (PC), a marker of protein oxidation, concentrations were 36% and 38% greater in RES and OVER offspring, respectively, compared with CON (P ≤ 0.01). The decrease in antioxidant activities and increase in products of protein and lipid oxidation in offspring from poorly nourished dams suggests dysregulation in skeletal muscle oxidative status that may contribute to the negative consequences observed in offspring. Future work should focus on determining the mechanistic role of skeletal muscle oxidative stress in the decreased quantity and quality of animal protein products and identifying potential strategies to mitigate alterations in oxidative status as a result of poor maternal nutrition during gestation.

Phosphorus heteroatom doped BiOCl as efficient catalyst for photo-piezocatalytic degradation of organic pollutant and unveiling the mechanism: Experiment and DFT calculation

A novel phosphorus heteroatom doped bismuth oxychloride (P-BiOCl) catalyst was synthesized and the photo-piezocatalytic degradation of rhodamine B dye performances were explored under the ultrasound vibration and light illumination. The P-BiOCl exhibited excellent photo-piezocatalytic degradation activity, such as an ultra-high reaction kinetic rate constant of 0.3961 min−1, efficient degradation efficiency (94.7 % within 8 min) and excellent stability compared to solely piezocatalysis and photocatalysis. More impressively, these outstanding performances of P-BiOCl exceeded pure BiOCl and most other catalytic materials systems. The relevant experimental and density functional theory (DFT) calculation results were exhibited to clarify enhanced photo-piezocatalytic mechanism. The introduction of P heteroatom could reduce the bandgap of BiOCl, modulate electronic structure and charge redistribution, provide novel electron channel to promote electron transfer and restrain charge carriers recombination. Additionally, P-doped could also enhance the adsorption of oxygen and water molecules, promote intrinsic catalytic activity, leading to the increased production of active free radicals ·O2– and ·OH, thus significantly boosting the efficiency of organic pollutant degradation. This work provides a comprehensive understanding of heteroatom doping enhancing photo-piezocatalytic activity and presents a potential new strategy for designing highly efficient catalysts for wastewater treatment.

Oxygen, the Paradox of Life and the Eye

Oxidative stress, caused by the formation of free radicals, such as reactive oxygen species (ROS), leads to cell and tissue degradation, contributing to various diseases and aging. While oxygen is essential for aerobic organisms, it inevitably causes oxidative stress. Antioxidants protect against damage from free radicals, and oxidative stress arises when an imbalance occurs between free radical production and antioxidant defenses. However, when investigating whether an excess of antioxidants, almost eliminating oxidative stress, could benefit aging and disease susceptibility, it was observed that a basic level of oxidative stress appears necessary to maintain the correct homeostasis of tissues and organs and life in general. Therefore, this review aimed to compile the most significant and recent papers characterizing and describing the dual role of oxygen as a molecule essential for life and as a precursor of oxidative stress, which can be detrimental to life. We conducted targeted searches in PubMed and Google browsers to gather all relevant papers. We then focused on the eye, an organ particularly vulnerable due to its high metabolic activity combined with direct exposure to light and environmental pollutants, which produces a substantial number of free radicals (mainly ROS). We present a curated selection of relevant literature describing the main ocular pathologies of the posterior and anterior segments of the eye, highlighting oxidative stress as a significant contributing factor. Additionally, we report how endogenous and exogenous antioxidants can mitigate the development and progression of these diseases. Finally, we consider a frequently overlooked aspect: the balance between oxidants and antioxidants in maintaining the homeostatic equilibrium of tissues and organs. It is widely recognized that when oxidants overwhelm antioxidants, oxidative stress occurs, leading to negative consequences for the organism's homeostasis. However, we emphasize that a similarly dangerous situation can arise when the presence of antioxidants overwhelms the production of free radicals, drastically reducing their amount and adversely affecting aging and longevity. Unfortunately, no specific studies have addressed this particular situation in the eye.

The Sirt1/Nrf2 pathway is a key factor for drug therapy in chemotherapy-induced cardiotoxicity: a Mini-Review.

The likelihood of survival for cancer patients has greatly improved due to chemotherapy medicines. However, these antitumor agents might also have unfavorable effects on the cardiovascular system, which could result in sudden or gradual cardiac failure. The production of free radicals that result in oxidative stress appears to be the key mechanism by which chemotherapy-induced cardiotoxicity (CIC) happens. Reports suggest that the Sirtuin-1 (Sirt1)/Nuclear factor E2-associated factor 2 (Nrf2) signaling pathway has been considered an alternative path for counteracting cardiotoxicity by suppressing oxidative stress, inflammation, and apoptosis. This review concludes recent knowledge about CIC with a special focus on the anti-oxidative regulation properties of the Sirt1/Nrf2 pathway.

The association between dietary antioxidant quality score and intensity and frequency of migraine headaches among women: a cross-sectional study

BackgroundMigraine is an episodic disorder and a frequent form of headache. An impaired balance between free radical production and an impaired antioxidant defense system leading to oxidative damage may play a major role in migraine etiology. We sought to investigate whether dietary antioxidant quality score (DAQS) is associated with migraine intensity and frequency among women suffering from migraine.MethodsThis cross-sectional study was conducted on 265 women. The data related to anthropometric measures and dietary intake were collected. DAQS score was calculated based on FFQ (food frequency questionnaire) vs. the reference daily intake (RDI) quantity. To measure migraine intensity, the migraine disability assessment questionnaire (MIDAS) and visual analog scale (VAS) were used. The frequency of headaches was defined as the days the participants had headaches in the last month and a 30-day headache diary was used.ResultsThe results of the study demonstrated that VAS, MIDAS, and frequency of headaches were reduced significantly from the low DAQS (poor quality of antioxidants) to high DAQS (high quality of antioxidants) after adjusting covariates. Also, multinomial regression showed there was an inverse association between higher DAQS and the frequency of headaches. In the adjusted model, subjects with the higher DAQS were 69% less likely to have moderate migraine disability, compared with those with the lower DAQS. Linear regression showed, there was an inverse association between vitamin C intake and the grades of pain severity.َAlso in a crude model, a negative association was found between vitamin E and the frequency of headaches.ConclusionIn conclusion, Participants with higher DAQS had lower migraine intensity and headache frequency. In addition, the consumption of vitamin C may potentially associate with decreasing the severity of headaches. Dietary antioxidants should be monitored closely in individuals suffering from migraine.

Vitamin K3 derivative inhibits androgen receptor signaling in targeting aggressive prostate cancer cells.

Prostate cancer (PCa) is the second critical cause of cancer-related deaths, with African Americans dying at higher rates in the U.S. The main reasons for the higher mortality rate are ethnic differences and lack of understanding of prostate cancer biology and affordable treatments, as well as the financial burden of African American men to obtain the most effective and safe treatments. The effect of micronutrients, including Vitamin K, on various cancer cell lines has been widely studied, but the potential anticancer effect of VK3-OCH3, an analog of vitamin K3 (Menadione), on African American prostate cancer has not been evaluated. In this study, we compared the anticancer effect of VK3-OCH3 on targeting African American derived PCa cell lines namely RC77-T and MDA-PCa-2b. Our results show that VK3-OCH3 significantly inhibits the proliferation of both RC77-T and MDA-PCa-2b African American PCa cells and promotes apoptosis, and the underlying mechanism of cell death appears to be similar in both the cell lines. Notably, VK3-OCH3 inhibits colony-forming ability and induces apoptosis by blocking the cell cycle at G0 in African American PCa cells. VK3-OCH3 also acts as an anti-metastatic agent by inhibiting the migration ability of the metastatic properties of African American PCa cells. The cell death of African American PCa cells mediated by VK3-OCH3 is associated with the production of free radicals, such as intracellular and mitochondrial reactive oxygen species (ROS). Interestingly, antioxidants such as N-Acetylcysteine (NAC) and Glutathione (GSH) effectively negated the oxidative stress induced by VK3-OCH3 on PCa cell lines derived from African American patients. Of note, VK3-OCH3 reduces androgen receptor and prostate-specific antigen expression in these PCa cells. Furthermore, molecular dynamic studies reiterated that VK3-OCH3 strongly binds to the androgen receptor, suggesting that the androgen receptor is the potential molecular target of VK3-OCH3. In addition, Western blot analysis showed that VK3-OCH3 reduces the expression of androgen receptor, TRX2, and anti-apoptotic signaling molecules such as Bcl-2 and TCTP in the MDA-PCa-2b metastatic PCa cellular model. In conclusion, our results suggested that VK3-OCH3 is a promising anticancer agent that could potentially reduce the mortality rates of African American PCa patients, warranting further preclinical and translational studies.

Banisteriopsis caapi extract: Implications for neuroinflammatory pathways in Locus coeruleus lesion rodent model

Ethnopharmacology relevanceAyahuasca is a beverage obtained from the decoctions of Banisteriopsis caapi (Spruce ex Griseb.) Morton and Psychotria viridis Ruiz & Pav., used throughout the Amazon as a medicinal beverage for healing and spiritual exploration. The Banisteriopsis caapi extract consists of harmine, harmaline, and tetrahydroharmine (THH); which inhibit the isoforms of monoamine oxidase A and B. In the central nervous system (CNS), it can increase the norepinephrine (NE) concentration, produced in the Locus coeruleus (LC), reducing inflammation that is associated with some neurological disease, such as Parkinson's disease and Alzheimer's disease. Aim of the studyevaluate the effects of treatment with B. caapi extract on the neuroinflammatory profile in animals with selective LC lesions. Material and methodsmale Wistar rats with LC lesions induced by 6-hydroxydopamine were treated with B. caapi extract. Subsequently, behavioral tests were conducted, including the elevated plus maze, rotarod, and open field. Tyrosine hydroxylase positive (TH+) neurons and IBA-1 positive microglia were quantified from the LC inflammatory markers and free radical products were assessed. ResultsBoth 6-Hydroxydopamine hydrochloride and the Banisteriopsis caapi extract causes reduction of LC neurons, at the concentration and frequency used. The LC depletion and the treatment of B. caapi extract interfere with locomotion. B. caapi extract and the LC lesion increased the number and activation of inflammatory cells, such as microglia. B. caapi extract decreases IL-10 in the hippocampus and BDNF gene expression. ConclusionThis study suggests that B. caapi extract (at the concentration and frequency used) promotes noradrenergic neuron depletion and creates a proinflammatory environment in the CNS.

Photodynamic therapy on mRNA levels in bacteria.

Antimicrobial photodynamic therapy (aPDT) has shown efficacy in inactivating different bacterial species by photosensitizer-induced free radical production. Despite aPDT is considered unable to cause resistant strains, enzymatic pathways for detoxification of reactive oxygen species and transmembrane photosensitizer efflux systems could cause resistance to aPDT. Resistance mechanisms can be evaluated by measurement of mRNA from by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Thus, the aim of this study was to access the mRNA level data obtained by RT-qPCR in bacterial cells submitted to photodynamic therapy. Studies performed on mRNA levels in bacteria after PDT were assessed on MEDLINE/Pubmed. The mRNA levels from genes related to various functions have been successfully evaluated in both Gram-positive and -negative bacteria after aPDT by RT-qPCR. Such an approach has improved the understanding of aPDT-induced effects, and reinforced the effectiveness of aPDT on bacteria, which can cause infections in different human tissues.

Fortification of Dairy Products using Plant-derived Bioactive Compounds

Dairy products are rich sources of essential vitamins, minerals, and various bioactive components crucial for biochemical and physiological well-being. Over the past decade, there has been a growing interest in dairy products fortified with antioxidants and plant extracts. This increased interest stems from the vital role dairy plays in human nutrition and the demand for “natural preservatives”. One particularly promising approach involves enhancing dairy products with plant-derived antioxidants. Antioxidants are critical in neutralizing and scavenging free radicals, constantly produced within the body. Free radicals can damage vital molecules and contribute to the development of chronic diseases, such as cardiovascular disease, diabetes, and even cancer. This damage is often associated with oxidative stress, a condition where the body's natural antioxidant defenses are overwhelmed by free radical production. This review examines the growing trend of fortifying dairy products (milk, ice cream, cheese, and yogurt) with natural ingredients to enhance their nutritional value and functionality. The review focuses on using plant extracts, herbs, spices, and other natural sources, exploring their fortification potential without compromising organoleptic properties. Finally, the review focuses on the potential benefits of incorporating plant-derived bioactive compounds to fortify the antioxidant capacity of milk and dairy products.

Potentials of Zingiber officinale and Allium sativum ethanol extracts to inhibit oxidative stress and inflammation resulting from cancer inducement with 7,12-dimethylbenz[a]anthracene

Oxidative stress is the outcome of an imbalance between systemic manifestation of reactive oxygen species and a biological systems ability to readily detoxify the reactive intermediates in order to repair the resulting damage. This imbalance causes toxic effects through production of peroxides and free radicals. This study evaluated the potentials of Zingiber officinale and Allium sativum ethanol extracts to inhibit oxidative stress and inflammation resulting from cancer inducement with 7,12-dimethylbenz[a]anthracene (DMBA) using female Swiss virgin Albino rats of 7–8 weeks old. The plants were extracted with ethanol and assayed for tumor necrosis factor-alpha (TNF-α) and nuclear factor kappa B (NFk-β) to indicate inflammatory responses; malondialdehyde, superoxide dismuthase, catalase and glutathione as indicators of oxidative stress.. All assays were done using standard methods. Phytocompounds in Zingiber officinale were: alkaloids, tannins, flavonoids, steroids and terpenoids while those in Allium sativum were alkaloids, saponins, flavonoids, and glycosides. The actual lethal doses (LD50) of Zingiber officinale, Allium sativum and combination of the two were 8,660, 4,472, and 5,477 mg/kg body weight respectively. Zingiber officinale and Allium sativum ethanol extracts either as mono-therapy or in combination decreased the serum levels of malondialdehyde, and increased superoxide dismuthase, catalase and glutathione. They also decreased tumor necrosis factor-alpha and nuclear factor kappa B significantly (p˂0.05) when compared with control group. These were most remarkable in group 8. In conclusion, Zingiber officinale and Allium sativum ameliorated the oxidative stress and inflammation responses most remarkably when given at the proportion of ZO:AS = 6:4 (318:212 mg/kg body weight).

Enhanced adsorption of tylosin by ordered multistage porous carbon and efficient in-situ regeneration of saturated adsorbents by activated persulfate oxidation: Performance, mechanism and multiple cycles

In this study, a novel ordered multistage porous carbon (OMPC) with a micro-mesoporous structure was prepared and used for the removal of tylosin (TYL). The porous material, carbonized at 900 °C (OMPC-900), exhibited micro-mesoporous structures with pore sizes of 0.71 nm and 3.63 nm, while had a specific surface area of 1300.02 m2 g−1. OMPC-900 demonstrated a maximum adsorption capacity of 341.28 mg g−1 for TYL in water by electrostatic attraction, hydrogen bonding, π-π interactions, and pore-filling mechanisms, which is 6.41 times higher than that of activated carbon. The TYL-saturated adsorbents could be efficiently regenerated by in-situ oxidation through the activation of persulfate (PDS), achieving a regeneration rate of 94.17%, significantly higher than that of activated carbon (55.22%). The excellent regeneration performance may be attributed to the presence of -C=O and graphitic carbon in the adsorbent, which promotes the production of free radicals (•OH, SO4•- and •O2−) and non-free radicals. Among these, the non-radical pathways (1O2 and electron transfer) played a key role in the degradation of TYL loaded on the adsorbent. OMPC-900 maintained stable regenerative adsorption performance of 80.85% after five in-situ regeneration, and the normalized adsorption capacity per unit surface area increased from 0.21 to 0.39 mg m−2, which may be due to that the increase in oxygen-carbon ratio and surface defects improved the adsorption sites activity of the regenerated adsorbent. In comparison to conventional pyrolysis and organic solvent elution, oxidative regeneration through the activation of PDS is a more efficient and sustainable method.

Evaluation of antioxidant prophylactic effects of parsley (Petroselinum crispum) on sepsis following cecal ligation and puncture

Objective: Sepsis causes the release of free oxygen radicals that disrupt membrane integrity, and damage to Mitochondria due to the production of free oxygen radicals and oxidation leads to exacerbation of sepsis, Cecal ligation and puncture (CLP) in rats mimics the characteristics and course of clinical sepsis (Hubbard et al., 2005). Methods: We evaluated the antioxidant effects of Petroselinum crispum (Pc) in a cecal ligation and puncture (CLP)-induced rat sepsis model, in a rat model of sepsis caused by cecal ligation and puncture (CLP). Wistar albino rats were separated into four groups of eight groups: a sham group with incised and sutured abdomens; a Pc extract (PcE) group, which was given 2 g/kg parsley extract for 14 days by gastric gavage; a CLP group, which was subjected to sepsis caused by CLP; and a PcE + CLP group, which was given parsley extract for 14 days. PcE was given for 14 days, after which sepsis was induced via the CLP procedure. The groups were compared in terms of hemogram, biochemical and histological characteristics. Results: The administration of PcE before CLP-induced sepsis increases neutrophil counts, PLTs and TASs, which decrease with sepsis, and decreases biochemical changes (BUN, AST, ALT, LDH, TOS, and OSI), which increase with sepsis, to protect against sepsis. Compared with that in the CLP group, the severity of intestinal infiltration was significantly lower in the PcE + CLP group; however, the degree of epithelial damage in the PcE + CLP group was similar to that in the CLP group. In the PcE + CLP group, the crypt and villus lengths were greater, and the decrease in Paneth cell degranulation intensity was greater than that in the CLP group. Conclusion: Additionally, the morphology of the cells in the PcE + CLP group was similar to that in the sham group. PcE has potential as a prophylactic agent for sepsis.

Free Radical Production Induced by Nitroimidazole Compounds Lead to Cell Death in Leishmania infantum Amastigotes.

Leishmania infantum is the vector-borne trypanosomatid parasite causing visceral leishmaniasis in the Mediterranean basin. This neglected tropical disease is treated with a limited number of obsolete drugs that are not exempt from adverse effects and whose overuse has promoted the emergence of resistant pathogens. In the search for novel antitrypanosomatid molecules that help overcome these drawbacks, drug repurposing has emerged as a good strategy. Nitroaromatic compounds have been found in drug discovery campaigns as promising antileishmanial molecules. Fexinidazole (recently introduced for the treatment of stages 1 and 2 of African trypanosomiasis), and pretomanid, which share the nitroimidazole nitroaromatic structure, have provided antileishmanial activity in different studies. In this work, we have tested the in vitro efficacy of these two nitroimidazoles to validate our 384-well high-throughput screening (HTS) platform consisting of L. infantum parasites emitting the near-infrared fluorescent protein (iRFP) as a biomarker of cell viability. These molecules showed good efficacy in both axenic and intramacrophage amastigotes and were poorly cytotoxic in RAW 264.7 and HepG2 cultures. Fexinidazole and pretomanid induced the production of ROS in axenic amastigotes but were not able to inhibit trypanothione reductase (TryR), thus suggesting that these compounds may target thiol metabolism through a different mechanism of action.

The Effects of Olive Oil (Olea Europaea L.) on Cathallase Enzyme Levels in White Rats (Rattus Norvegicus) Wistar Strain of Obese Male

Obesity is a condition of the body resulting from excessive fat accumulation which leads to health problems. The increase in fat metabolism affects increased production of free radicals in the circulation and in adipocyte cells. Free radicals that increase in the body are not in line with antioxidant enzymes, causing a condition called oxidative stress. The body's defense mechanism against free radicals is the synthesis of antioxidants. When there is a decrease in the activity of endogenous antioxidants such as the catalase enzyme, it provides a strong indication of oxidative stress. The presence of polyphenols and monounsaturated fatty acids in olive oil is useful for preventing chronic damage that causes oxidative stress. The catalase enzyme can be used as a parameter for an uncontrolled increase in ROS (Reactive Oxygen Species) or disruption of the function of the antioxidant defense system. To determine changes in levels of the catalase enzyme in an obese male Wistar strain white rat (Rattus norvegicus) animal model that was given olive oil. This research used a true experimental laboratory with a pre- post test design. The results of the study were significant changes in catalase enzyme levels in the olive oil intervention group (p-value 0.003<0.05) on day 14 and day 28 with (p-value 0.002<0.05 and 0.005<0.05). In the group given olive oil, the effect on the level of catalase enzyme was most significant on day 28 (p-value 0.002<0.05).

Effects of Fasting on THP1 Macrophage Metabolism and Inflammatory Profile.

Fasting can affect the body's inflammatory response, and this has been linked to potential health benefits, including improvements for people with rheumatic diseases. In this work, we evaluated, in vitro, how changes in nutrient availability alter the inflammatory response of macrophages. Macrophage-differentiated THP1 cells were cultured, deprived of FCS or subjected to cycles of FCS deprivation and restoration to mimic intermittent fasting. Changes in the macrophage phenotype, the cells' response to inflammatory stimuli and the level of mitochondrial alteration were assessed. The results indicate that while periods of serum starvation are associated with a decrease in IL1β and TNFα expression, consistent with an anti-inflammatory response, intermittent serum starvation cycles promote a pro-inflammatory phenotype. Rapid changes in reducing capacity and mitochondrial response were also observed. Of note, while some changes, such as the production of oxygen free radicals, were reversed with refeeding, others, such as a decrease in reducing capacity, were maintained and even increased. This study shows that different fasting protocols can have diverging effects and highlights that time-limited nutrient changes can significantly affect macrophage functions in cell cultures. These findings help elucidate some of the mechanisms by which specific fasting dietary interventions could help control inflammatory diseases.

Nigella sativa L. and its bioactive and nutraceutical components in the management of diabetic peripheral neuropathy.

Diabetes-induced hyperglycemia leads to excessive production of oxygen free radicals, inflammatory cytokines, and oxidative stress, which initiates diabetic peripheral neuropathy(DPN). Currently, this condition affects 20% of adults with diabetes. Despite significant advances in the treatment of diabetes, the incidence of its complications, including DPN, is still high. Thus, there is a growing research interest in developing more effective and treatment approaches with less side effects for diabetes and its complications. Nigella sativa L. (NS) has received much research attention as an antioxidant, anti-yperglycemic factor, and anti-inflammatory agent. This natural compound demonstrates its antidiabetic neuropathy effect through various pathways, including the reduction of lipid peroxidation, the enhancement of catalase and superoxide dismutase enzyme activity, and the decrease in inflammatory cytokine levels. The present review focuses on the bioactive and nutraceutical components of black cumin (Nigella sativa L.) and their effects on DPN. In addition, we have also summarized the findings obtained from several experimental and clinical studies regarding the antidiabetic neuropathy effect of NS in animal models and human subjects.

Degradation pathways and product formation mechanisms of asphaltene in supercritical water

Asphaltene is the compound with the most complex structure and the most difficult degradation in oily sludge, which is the key to limit the efficiency of supercritical water oxidation treatment of oily sludge. In this paper, the supercritical water oxidation process of asphaltene was investigated in terms of free radical reaction, degradation pathway, and product generation mechanism using ReaxFF molecular dynamics simulation method. The results showed that increasing temperature, increasing O2, and increasing H2O have different effects on HO2·generation. Benzene rings undergo fusion and condensation through hydrogenation abstraction and oxygen addition reactions, subsequently breaking down into long-chain alkanes. Increasing O2 can effectively promote the ring-opening of nitrogen-containing heterocycles. -COOH is the most important intermediate fragment for CO and CO2 generation, and there is a reaction competition with -CHO3 and -CO3. When the number of oxygen molecules increases from 300 to 700, the reaction frequency of -CHO3 and -CO3 to generate CO and CO2 increases by 17.14 % and 12.77 %·H2O determines the production of H2 by controlling the number of H·radicals present. As the amount of H2O increases from 500 to 1500, the product ratio of H2 increases from 12.73 % to 21.31 %. Environmental implicationAsphaltene is the most structurally complex organic matter in oily sludge, and its presence makes it difficult for oily sludge to be completely degraded by conventional treatment methods such as pyrolysis and incineration. Polycyclic aromatic hydrocarbons (PAHs) represented by asphaltene increase the carcinogenicity and mutagenicity of oily sludge, and even irreversibly pollute soil and groundwater. Supercritical water oxidation, as an efficient organic waste treatment technology, can realize harmlessness in a green and efficient way. So the study on the mechanism of supercritical water oxidation of asphaltene is of great significance for environmental protection.