Oxidative Cell Damage Research Articles

The endogenous antioxidant ability of royal jelly in Drosophila is independent of Keap1/Nrf2 by activating oxidoreductase activity.

Royal jelly (RJ) is a biologically active substance secreted by the hypopharyngeal and mandibular glands of worker honeybees. It is widely claimed that RJ reduces oxidative stress. However, the antioxidant activity of RJ has mostly been determined by in vitro chemical detection methods or by external administration drugs that cause oxidative stress. Whether RJ can clear the endogenous production of reactive oxygen species (ROS) in cells remains largely unknown. Here, we systematically investigated the antioxidant properties of RJ using several endogenous oxidative stress models of Drosophila. We found that RJ enhanced sleep quality of aging Drosophila, which is decreased due to an increase of oxidative damage with age. RJ supplementation improved survival and suppressed ROS levels in gut cells of flies upon exposure to hydrogen peroxide or to the neurotoxic agent paraquat. Moreover, RJ supplementation moderated levels of ROS in endogenous gut cells and extended lifespan after exposure of flies to heat stress. Sleep deprivation leads to accumulation of ROS in the gut cells, and RJ attenuated the consequences of oxidative stress caused by sleep loss and prolonged lifespan. Mechanistically, RJ prevented cell oxidative damage caused by heat stress or sleep deprivation, with the antioxidant activity in vivo independent of Keap1/Nrf2 signaling. RJ supplementation activated oxidoreductase activity in the guts of flies, suggesting its ability to inhibit endogenous oxidative stress and maintain health, possibly in humans.

Azithromycin induces neurotoxicity in zebrafish by interfering with the VEGF/Notch signaling pathway

Azithromycin (AZM) is a widely used antibiotic in both human and veterinary medicine, and its use has significantly increased during the COVID-19 pandemic. However, potential adverse effects of AZM on aquatic organisms have not been well studied. In this study, we explored the neurotoxicity of AZM in zebrafish and delved into its underlying mechanisms. Our results showed that AZM exposure resulted in a spectrum of detrimental effects in zebrafish, encompassing abnormal behaviors, damaged neuronal development, aberrant lateral line nervous system development, vascular malformations and perturbed expression of genes related to neural development. Moreover, we observed a concentration-dependent exacerbation of these neurotoxic manifestations with increasing AZM concentrations. Notably, AZM induced excessive cell apoptosis and oxidative stress damage. In addition, alterations in the expression levels of the genes involved in the VEGF/Notch signaling pathway were evident in AZM-exposed zebrafish. Consequently, we hypothesize that AZM may induce neurotoxicity by influencing the VEGF/Notch signaling pathway. To validate this hypothesis, we introduced a VEGF signaling inhibitor, axitinib, and a Notch signaling agonist, valproic acid, alongside AZM exposure. Remarkably, the administration of these rescue compounds significantly mitigated the neurotoxic effects induced by AZM. This dual verification provides compelling evidence that AZM indeed induces neurotoxicity during the early developmental stages of zebrafish, primarily through its interference with the VEGF/Notch pathway. Innovatively, our study reveals the molecular mechanism of AZM-induced neurotoxicity from the perspective of the close connection between blood vessels and nervous system. These findings provide new insights into the potential mechanisms underlying the neurotoxic effect of antibiotics and highlight the need for further investigation into the ecotoxicological effects of antibiotics on aquatic organisms and the potential risks to human health.

The pentose phosphate pathway in health and disease.

The pentose phosphate pathway (PPP) is a glucose-oxidizing pathway that runs in parallel to upper glycolysis to produce ribose 5-phosphate and nicotinamide adenine dinucleotide phosphate (NADPH). Ribose 5-phosphate is used for nucleotide synthesis, while NADPH is involved in redox homoeostasis as well as in promoting biosynthetic processes, such as the synthesis of tetrahydrofolate, deoxyribonucleotides, proline, fatty acids and cholesterol. Through NADPH, the PPP plays a critical role in suppressing oxidative stress, including in certain cancers, in which PPP inhibition may be therapeutically useful. Conversely, PPP-derived NADPH also supports purposeful cellular generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) for signalling and pathogen killing. Genetic deficiencies in the PPP occur relatively commonly in the committed pathway enzyme glucose-6-phosphate dehydrogenase (G6PD). G6PD deficiency typically manifests as haemolytic anaemia due to red cell oxidative damage but, in severe cases, also results in infections due to lack of leucocyte oxidative burst, highlighting the dual redox roles of the pathway in free radical production and detoxification. This Review discusses the PPP in mammals, covering its roles in biochemistry, physiology and disease.

Intervention effects of sulfate glycosaminoglycan from swim bladder against arsenic-induced damage in IEC-6 cells

In this study, a purified macromolecular sulfate glycosaminoglycan whose structural characterization is similar to chondroitin sulfate from the swim bladder of Aristichthys nobilis, named SBSG, was used to explore the intervention effects on arsenic-induced intestinal epithelial cells (IEC-6) damage. Arsenic exposure led to cell membrane rupture, mitochondrial dysfunction, oxidative damage, and down-regulation of tight junction proteins expression. Treatment with SBSG could alleviate arsenic exposure-induced cell damage by decreasing the extracellular lactate dehydrogenase activity and influencing mitochondrial membrane potential, reactive oxygen species level, malondialdehyde content, and anti-oxidative enzyme activity. On the other hand, SBSG could promote nitric oxide production to achieve potential immunoregulation. The Western blot showed that intervention of SBSG mainly could restrain the activation of the JNK signaling pathway and up-regulate the expression of ZO-1 against arsenic-induced cell damage. This study provides a new perspective for understanding the heavy metal detoxification of SBSG on the intestinal and indicates that SBSG could be used as natural antioxidant resistant to heavy metal toxicity.

Study of Serum Ferritin and Glycemic Status in Type II Diabetic Patients

Introduction: Diabetes mellitus has often found to be associated with iron dysregulation, manifested by increased serum ferritin level. Iron is essential for beta- cell insulin secretion, although, increasing concentration of iron and ferritin induce oxidative damage and dysfunction of pancreatic beta cells, leading to resistance to insulin, thus, consequent in hyperglycemia. Objective: To observe the association between serum ferritin and HbA1c concentration among type 2 DM patients. Methods: With an observational study design, the present study has been done among 63 purposively selected type 2 diabetic patients who attended the selected pathology institute during the period of January to June, 2021. Following availing the ethical approval from concerning ethical review committee and informed written consent of the patients, data regarding age, sex, height, weight, body mass index (BMI), diabetic duration, HbA1c concentration and serum ferritin level has been collected and recorded in a semi-structured questionnaire. Data were analyzed using Statistical Package for Social Science (SPSS) 20. Results: The study recorded that, the mean serum ferritin level was significantly higher among the poor glycemic control group than the good glycemic control group of respondents (p<0.05) though no statistically significant difference was observed in terms of age, sex, BMI or diabetic duration among the groups (p>0.05). Conclusion: Higher serum ferritin level among diabetic patients with poor glycemic control may indicate that there is a pathological role of serum ferritin to induce changes in glycemic status, which requires further in depth studies to apprehend about the mechanism. JAFMC Bangladesh. Vol 18, No 2 (December) 2022: 07-10

Silencing of peroxiredoxin III inhibits formaldehyde-induced oxidative damage of bone marrow cells in BALB/c mice.

Formaldehyde (FA) is associated with the occurrence of leukemia, and oxidative stress is considered to be a major reason. As an endogenous biomarker of oxidative stress, few studies focus on the relationship between peroxiredoxin III (PrxIII) and FA toxicity. Our previous research observed high expression of PrxIII occurred in the process of apoptosis of bone marrow cells (BMCs) induced by FA, however the exact mechanism is unclear. Therefore, this paper aimed to explore the possible association between FA toxicity and PrxIII gene. We first, used a Cell Counting Kit-8 (CCK-8) to detect the viability of BMCs after they were exposed to different doses of FA (50, 100, 200 μmol/L) for different exposure time (12, 24, 48 h), then chose 24 h as an exposure time to detect the expression of PrxIII for exposing different doses of FA by Quantitative reverse transcription-PCR (qRT-PCR) and Western blot analysis. Based on our preliminary experimental results, we chose 100 μmol/L FA as an exposure dose to expose for 24 h, and used a small interfering RNA (siRNA) to silenced PrxIII to examine the cell viability by CCK-8, reactive oxygen species (ROS) level by DCFH-DA, apoptosis by Annexin V/PI double staining and cell cycle by flow cytometry (FCM) so as to explore the possible regulatory effect of PrxIII silencing on FA-induced bone marrow toxicity. High expression of PrxIII occurred in the process of FA-induced oxidative stress. Silencing of PrxIII prevented FA from inducing oxidative stress, thus increasing cell viability, decreasing ROS level, rescuing G0 -G1 and G2 -M arrest, and reducing cell apoptosis. PrxIII silencing might be a potential target for alleviating FA-induced oxidative damage.

7, 12- Dimethylbenz[a]anthracene: A potent and multivariant Chemical carcinogen

Cancer is currently the second major cause of mortality globally. It is a collection of disorders categorized as abnormal cell development which can infiltrate and can spread to countless sections of the body. It has been essentially brought about by genetic and environmental sources mainly, countless patients have impacted by ecological factors like polycyclic aromatic hydrocarbons (PAHs). However, many PAHs in the ecosystem are generated from natural factors like direct combustion, petroleum and volcanic activity. Among these, 7,12 dimethylbenz[a]anthracene (DMBA) has been widely recognized for its capability to induce carcinogenesis in animals and humans. The carcinogenic activity of DMBA indicates the impact of well-differentiated tumors and it is recognized for generating DNA-reactive species that increase the oxidative damage in cells through their metabolism. Additionally, the configuration of DNA adducts and oxidative intermediates acquired from DMBA metabolism impairs prominent cellular activities by harming lipid and protein barriers. DNA adduct is made up of highly reactive intermediates. DMBA-induced cancer displayed higher expression of aryl hydrocarbon receptor (AhR), c-Myc, cyclinD1, activation of upstream regulatory mechanisms and frequent detection of NF-κB pathway components. In this study, we emphasized the growth of several cancers and the kinetic impact of DMBA to probable chemical carcinogenic activities.

Exosomes secreted by mesenchymal stem cells delay brain aging by upregulating SIRT1 expression

The increase in the aging population has seriously affected our society. Neurodegenerative diseases caused by aging of the brain significantly impact the normal life of the elderly, and delaying brain aging is currently the focus of research. SIRT1 is a viable therapeutic target, and there is mounting evidence that it plays a significant role in the aging process. Mesenchymal stem cell-derived exosomes (MSC-Exos) have gained widespread interest as nanotherapeutic agents because of their ability to be injected at high doses to reduce the immune response. The present study focused on the ameliorative effect of MSC-Exos on aging mice and the potential mechanisms of this effect on cognitive impairment and brain aging. In this study, we first tested the neuroprotective effects of MSC-Exos in vitro on H2O2-induced oxidative damage in BV2 cells. An in vivo SAMP8 rapid senescence mouse model showed that MSC-Exos significantly increased SIRT1 gene expression in senescent mice. In addition, MSC-Exos also had an anti-apoptotic effect and reduced oxidative stress in the brains of SAMP8 senescent mice. In conclusion, MSC-Exos may exert neuroprotective effects and help prevent brain senescence in SAMP8 mice by activating the SIRT1 signaling pathway.

Engineered coumarin accumulation reduces mycotoxin-induced oxidative stress and disease susceptibility.

Coumarins can fight pathogens and are thus promising for crop protection. Their biosynthesis, however, has not yet been engineered in crops. We tailored the constitutive accumulation of coumarins in transgenic Nicotiana benthamiana, Glycine max and Arabidopsis thaliana plants, as well as in Nicotiana tabacum BY-2 suspension cells. We did so by overexpressing A. thaliana feruloyl-CoA 6-hydroxylase 1 (AtF6'H1), encoding the key enzyme of scopoletin biosynthesis. Besides scopoletin and its glucoside scopolin, esculin at low level was the only other coumarin detected in transgenic cells. Mechanical damage of scopolin-accumulating tissue led to a swift release of scopoletin, presumably from the scopolin pool. High scopolin levels in A. thaliana roots coincided with reduced susceptibility to the root-parasitic nematode Heterodera schachtii. In addition, transgenic soybean plants were more tolerant to the soil-borne pathogenic fungus Fusarium virguliforme. Because mycotoxin-induced accumulation of reactive oxygen species and cell death were reduced in the AtF6'H1-overexpressors, the weaker sensitivity to F. virguliforme may be caused by attenuated oxidative damage of coumarin-hyperaccumulating cells. Together, engineered coumarin accumulation is promising for enhanced disease resilience of crops.

Towards ductile and high barrier poly(L-lactic acid) ultra-thin packaging film by regulating chain structures for efficient preservation of cherry tomatoes

The irreconcilable paradox between barrier performance and ductility is a “stumbling block” restricting the development of poly(L-lactic acid) (PLLA) films in the packaging industry. In this work, we reported the fabrication of an ultra-thin PLLA-based film with barrier properties and ductility by adjusting the polarity and conformational behavior of the polymer chains. Firstly, a novel unsaturated poly(L-lactic acid-co-butyrate itaconate) P(LA-BI) copolymer containing CC double bonds was synthesized using melt polycondensation. The results reveal that the addition of 60 % of P(LA-BI) enables PLLA film to achieve an elongation at a break of 83.6 % due to P(LA-BI) containing partially branched structures, which resulted in the polymer chains being arranged more in a high-energy gg conformer. Meanwhile, because of the large number of CO polar groups in P(LA-BI), PLLA/P(LA-BI)60 film show CO2 and O2 permeability coefficients (CDP and OP) of 1.8 and 0.45 × 10−8 g·m·m−2·h−1·Pa−1 respectively, which means that it has excellent gas barrier properties. Moreover, PLLA/P(LA-BI)60 film shows a 33.3 % increase in CO2/O2 ratio and an excellent ultraviolet (UV) barrier performance compared to neat PLLA. Preservation results suggested that the CO2 and O2 levels within the package could be regulated by varying the amount of P(LA-BI) added. Among them, PLLA/P(LA-BI)40 film generated a more desirable CO2 and O2 atmosphere for cherry tomatoes preservation, which was reflected by the delaying of senescence, discoloration, and decay, inhibition of oxidative cell damage through reduced malondialdehyde production, and maintenance of nutritional and flavor substances in cherry tomatoes. This PLLA-based film offers the advantages of operational simplicity, environmental friendliness, and inexpensive cost, making it great promising for food preservation and other applications requiring barrier properties and ductility.

Hepatoprotective effect of p-Coumaric acid against KBrO3 -induced apoptosis in HepG2 cells.

In the present study, we investigated the effect of the p-Coumaric acid (PCA), a phenolic acid, on potassium bromate (KBrO3 ) induced oxidative damage, Ras/Raf/MEK signaling, and apoptosis in HepG2 cells. Our findings showed that PCA-treated cells prevented cytotoxicity compared with KBrO3- treated cells. Furthermore, KBrO3 -induced oxidative stress and lipid peroxidation was attenuated by PCA and it also increased the antioxidant levels such as SOD, CAT, and GPX. Additionally, PCA inhibited the KBrO3 -induced DNA damage in HepG2 cells. Moreover, PCA treatment suppressed the activation of Ras/Raf/MEK signaling and increased the expression of PRDX-1. In addition, PCA prevented the KBrO3 -induced apoptosis cascade by altering the expression of proapoptotic, Bax, caspase-3, and antiapoptotic, Bcl-2 proteins. The present study proves that PCA inhibited the KBrO3 -induced oxidative stress, DNA damage, and apoptotic signaling cascade in HepG2 cells.

Protective effect on pancreatic β cells of α-glucosidase inhibitors screened from Rehmannia glutinosa

Rehmannia glutinosa (RG) has been traditionally used as Chinese folk medicine for thousands of years. Catalpol in RG has significant therapeutic effects on type 2 diabetes mellitus (T2DM) and its complications. However, very limited study on other chemicals in RG for the treatment of diabetes. In this study, the compounds with α-glucosidase inhibitory activity in RG were screened and isolated by microfractionation bioactivity evaluation method. For the first time, 2,3,5,4′ -tetrahydroxystilbene-2-O-β-D-glucoside (THSG) was found in RG, and the inhibitory type of its enzyme inhibitory activity was determined. In addition, INS-1 cells were treated with H2O2 to establish a model of oxidative damage to pancreatic β cells, and the protective effect of THSG on oxidative damage of INS-1 cells was evaluated by detecting cell viability, content of malondialdehyde (MDA), superoxide dismutase (SOD) and insulin secretion levels. The results showed that THSG had a non-competitive reversible inhibitory effect on α-glucosidase (IC50 = 0.186 ± 0.003 μmol/mL). In the oxidative damage model of INS-1 cells treated with 80 μM THSG, cell viability was increased from 52.13% to 76.26%, content of MDA was decreased by 146.21%, and activity of SOD was increased by 26.27%. Compared with the model group, the total amount of insulin increased by 59.37%. Without the influence of H2O2, the total amount of insulin increased by 22.02% compared with the normal group. These results suggested that THSG could regulate blood glucose by effectively inhibiting α-glucosidase, alleviating oxidative damage to pancreatic β cells, and promoting insulin secretion.

Toxic effect of chronic exposure to polyethylene nano/microplastics on oxidative stress, neurotoxicity and gut microbiota of adult zebrafish (Danio rerio)

The rapid development of aquaculture industry has provided a large amount of high-quality animal protein, while the food safety caused by microplastics and nanoplastics (MP/NPs) has become a major concern. In addition, recent evidence has shown the potential toxic effect of PE-MP/NPs, highlighting the need for further research into their environmental and health impacts. Chronic exposure of polyethylene microplastics (PE-MPs) and nanoplastics (PE-NPs) on adult zebrafish were conducted in the present study for 21 d. Organ-dependent oxidative damage induced by MP/NPs was observed. Insignificant differences in neurotoxicity and dysbiosis of gut microbiota were found between MPs and NPs. Changes in glutathione S-transferase (GST), glutathione (GSH), catalase (CAT), lipid peroxidation (LPO), and superoxide dismutase (SOD) showed that MP/NPs induced oxidative damage in gill and intestinal cells of zebrafish. The inhibited AChE activity suggested the potential neurotoxicity of microplastics and nanoplastics (MP/NPs). In addition, chronic exposure increased the alpha-diversity of intestinal microbiota. At the phylum level, the average relative abundance of Proteobacteria increased from 29.73% (control group) to 66.10% (microplastics), 54.84% (nanoplastics) and 60.03% (combined exposure), respectively. Tenericutes decreased from 55.43% (control group) to 20.02% (microplastics), 22.44% (nanoplastics) and 31.77% (combined exposure), respectively. Overall, this study provides new insights and objective evidence for the toxicity assessment of PE-MPs.

Physiological and transcriptomic analysis reveal the crucial factors in heat stress response of red raspberry 'Polka' seedlings.

With global climate warming, recurring extreme heat and high temperatures irreversibly damage plants. Raspberries, known for their nutritional and medicinal value, are in high demand worldwide. Thus, it is important to study how high-temperature stress (HTS) affects raspberries. The physiological and biochemical responses and molecular genetic mechanisms of raspberry leaves to different HTS treatments were investigated: mild high temperature at 35°C (HT35), severe high temperature at 40°C (HT40), and the control at room temperature of 25°C (CK). The physiological results suggested that leaves in both the 35°C and 40°C treatments showed maximum relative conductivity at 4d of stress, increasing by 28.54% and 43.36%, respectively, compared to CK. Throughout the stress period (0-4 d), malondialdehyde (MDA) and soluble protein contents of raspberry leaves increased under HT35 and HT40 treatments, while soluble sugar content first decreased and then increased. Catalase (CAT) activity increased, superoxide dismutase (SOD) activity first increased and then decreased, and peroxidase (POD) activity gradually decreased. Photosynthetic and fluorescence responses of raspberry leaves showed the most severe impairment after 4d of stress. Transcriptomics results revealed significant alterations in 42 HSP family genes, two SOD-related differentially expressed genes (DEGs), 25 POD-related DEGs, three CAT-related DEGs, and 38 photosynthesis-related DEGs under HTS. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these DEGs were mainly enriched in photosynthesis-antenna proteins, pentose and glucuronide interconversion, phenylpropane biosynthesis, and indole alkaloid biosynthesis. HTS induced excessive ROS accumulation in raspberry leaves, causing oxidative damage in plant cells and subsequently reducing photosynthesis in raspberry leaves. This reduction in photosynthesis, in turn, affects photosynthetic carbon fixation and starch and sucrose metabolism, which, combined with phenol propane biosynthesis, mitigates the HTS-induced damage.

Biomarker changes and oxidative damage in living plant cells as new biomonitoring indicators for combined heavy metal stress assessment

The damage that combined heavy metals cause to plants is a global environmental problem, and it is also harder to detect compared with that from solitary heavy metal. One mechanism, heavy metal-induced cellular oxidative damage, occurs during the early stage of stress. For early monitoring of plant damage from combined heavy metals, in-situ detection of oxidative damage in soybean leaf cells was performed under the combined lanthanum (La, an emerging heavy metal pollutant) and lead (Pb, a conventional heavy metal pollutant) stress, using vitronectin-like protein (VN, a Lewis base that binds heavy metal ions) as a biomarker. A living cell electrochemical biosensor was used to detect the VN content in leaf cells by measuring the electrochemical output signal (electron-transfer resistance, Ret) coupled with oxidative damage indices, including reactive oxygen species (ROS), peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT), malondialdehyde (MDA), and the fresh weight and area of leaves, to comprehensively assess oxidative damage in living cells. The linear relationship between Ret (3884.85–6072.00 Ohm) and oxidative damage indices (145.01%–1196.02% and 135.53%–252.91% of the control group in ROS and MDA) was established under the combined La (10–80 μM) and Pb (5 μM) stress providing an early warning interval (127.38%–160.15% of the control group in Ret) for the occurrence of oxidative damage in living cells. This electrochemical biosensor was successfully used to detect changes in VN content and oxidative damage in leaves exposed to the combined La and Pb found in the rainfall of China, Africa, and Turkey. Real-time in-situ detection of biomarker changes and oxidative damage in plant cells caused by combined heavy metals provided a basis to monitor the degree of damage and obtain an early warning of heavy metal stress.

Polysaccharides from Tetrastigma Hemsleyanum Diels et Gilg ameliorated inflammatory bowel disease by rebuilding the intestinal mucosal barrier and inhibiting inflammation through the SCFA-GPR41/43 signaling pathway

In this study, the therapeutic effects of Tetrastigma hemsleyanum polysaccharide (THP) on inflammatory bowel disease (IBD) and its possible mechanisms were investigated based on the IBD mouse model induced by dextran sodium sulfate (DSS) and the lipopolysaccharide (LPS)-stimulated Caco-2 cell model. THP significantly alleviated the signs and symptoms of DSS-induced IBD mice, including the reduced weight, shortened colonic length, and increased colitis disease activity index. In vivo, THP significantly reduced inflammatory cell infiltration and oxidative damage, promoted intestinal mucus secretion, and restored the integrity of the intestinal epithelial barrier and mucus barrier. Furthermore, THP reversed the changes in the intestinal flora of colonized mice and restored the levels of short-chain fatty acids (SCFAs) by increasing the abundance of potentially beneficial bacteria and increasing the abundance of butyrate-producing bacteria. In addition, THP upregulated the expression of G-protein-coupled receptors (GPR41 and GPR43) both in vivo and in vitro. In summary, the current investigation showed that THP effectively protected against intestinal inflammation and impairment in the intestinal barrier in the setting of DSS-induced IBD, possibly by regulating gut microbiota structure and corresponding SCFA metabolites, and the pathway of SCFAs action may be related to SCFA-GPR41/43 signaling pathway.

Research of Pesticide Metabolites in Human Brain Tumor Tissues by Chemometrics-Based Gas Chromatography-Mass Spectrometry Analysis for a Hypothetical Correlation between Pesticide Exposure and Risk Factor of Central Nervous System Tumors.

Pesticides are widely used, resulting in continuing human exposure with potential health impacts. Some exposures related to agricultural works have been associated with neurological disorders. Since the 2000s, the hypothesis of the role of pesticides in the occurrence of central nervous system (CNS) tumors has been better documented in the literature. However, the etiology of childhood brain cancers still remains largely unknown. The major objective of this work was to assess the potential role of pesticide exposure as a risk factor for CNS tumors based on questionnaires and statistical analysis of information collected from patients hospitalized in the Neurosurgery Department of the Habib Bourguiba Hospital Medium in Sfax, Tunisia, during the period from January 1, 2022, to May 31, 2023. It also aimed to develop a simple and rapid analytical method by the gas chromatography-mass spectrometry technique for the research traces of pesticide metabolites in some collected human brain tumor tissues in order to more emphasize our hypothesis for such a correlation between pesticide exposure and brain tumor development. Patients with a history of high-risk exposure were selected to conduct further analysis. Chemometric methods were adapted to discern intrinsic variation between pathological and control groups and ascertain effective separation with the identification of differentially expressed metabolites accountable for such variations. Three samples revealed traces of pesticide metabolites that were mostly detected at an early age. The histopathological diagnosis was medulloblastoma for a 10-year-old child and high-grade gliomas for 27- and 35-year-old adults. The bivariate analyses (odds ratio >1 and P value <5%) confirmed the great probability of developing cancer by an exposure case. The Cox proportional hazards model revealed the risk of carcinogenicity beyond the age of 50 as a long-term effect of pesticide toxicity. Our study supports the correlation between pesticide exposure and the risk of development of human brain tumors, suggesting that preconception pesticide exposure, and possibly exposure during pregnancy, is associated with an increased childhood brain tumor risk. This hypothesis was enhanced in identifying traces of metabolites from the carbamate insecticide class known for their neurotoxicity and others from pyridazinone, organochlorines (OCs), triazole fungicide, and N-nitroso compounds known for their carcinogenicity. The 2D-OXYBLOT analysis confirmed the neurotoxicity effect of insecticides to induce oxidative damage in CNS cells. Aldicarb was implicated in brain carcinogenicity confirmed by the identification of oxime metabolites in a stress degradation study. Revealing "aziridine" metabolites from the OC class may better emphasize the theory of detecting traces of pesticide metabolites at an early age. Overall, our findings lead to the recommendation of limiting the residential use of pesticides and the support of public health policies serving this objective that we need to be vigilant in the postmarketing surveillance of human health impacts.

Protective Effects and Mechanisms of Pectolinarin against H2O2-Induced Oxidative Stress in SH-SY5Y Neuronal Cells.

This study aims to investigate the protective effects and mechanisms of pectolinarin against oxidative stress-induced cell damage in SH-SY5Y cells. Neurodegenerative diseases-such as Alzheimer's disease-are potentially associated with oxidative stress, which causes excessive production of reactive oxygen species (ROS) that damage DNA and proteins in neuronal cells. The results of this study demonstrate that pectolinarin can scavenge hydroxyl and nitric oxide radicals in a concentration-dependent manner. Moreover, pectolinarin significantly increased cell viability while reducing ROS production and LDH release in the hydrogen peroxide (H2O2)-induced control group. Additionally, Pectolinarin recovered protein expression from H2O2-altered levels back to close-to-normal SH-SY5Y cell levels for components of the oxidative stress, inflammation, and apoptosis pathways-such as nuclear factor erythroid 2-related factor 2 (Nrf2), kelch-like ECH-associated protein (Keap1), anti-heme oxygenase 1 (HO-1), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), B-cell lympho-ma-2 (Bcl-2) protein, and Bcl-2-associated X protein (Bax). These findings suggest that pectolinarin has the potential to be used as a plant material for functional foods to be applied in the treatment of neurodegenerative diseases, such as Alzheimer's disease, by mitigating oxidative stress-induced damage to neuronal cells.

High-speed counter-current chromatography assisted preparative isolation of phenolic compounds from the flowers of Chrysanthemum morifolium cv. Fubaiju.

Chrysanthemum morifolium cv. Fubaiju is rich in phenolic compounds with various benefits such as anti-inflammatory, antioxidant, and cardiovascular protection. In this study, 12 phenolic compounds, including five flavonoid glycosides and seven quinic acid derivatives, were successfully separated from the flowers of Chrysanthemum morifolium cv. Fubaiju by high-speed counter-current chromatography and preparative high-performance liquid chromatography. Ethyl acetate-n-butanol-acetonitrile-water-acetic acid (5:0.5:2.5:5:0.25, v/v/v/v/v) was selected as solvent system to separate six fractions from the flowers of Chrysanthemum morifolium cv. Fubaiju, and 20% aqueous acetonitrile (containing 0.1% formic acid) was chosen to be the elution solvent in preparative high-performance liquid chromatography for purifying the fractions above. Luteolin-7-O-β-D-glucoside (1), luteolin-7-O-β-D-glucuronide (2), apigenin-7-O-β-D-glucoside (3), luteolin-7-O-β-D-rutinoside (4), diosmetin-7-O-β-D-glucoside (5), chlorogenic acid (6), 1,5-dicaffeoylquinic acid (7), 1,4-dicaffeoylquinic acid (8), 3,4-dicaffeoylquinic acid (9), 3,4-dicaffeoyl-epi-quinic acid (10), 3,5-dicaffeoylquinic acid (11), and 4,5-dicaffeoylquinic acid (12) were isolated with purities all above 95%, respectively. In addition, all isolates were evaluated for their protective effects on H2 O2 -induced oxidative damage in adult retinal pigment epithelial cells.

The Effect of Garlic Decoction (Allium sativum L.) on The Histological Features of The Liver of Alloxan-induced Mice (Mus musculus)

Giving alloxan can cause disruption of insulin production resulting in hyperglycemia. Hyperglycemia causes Reactive Oxygen Species (ROS) resulting in oxidative stress and liver cell damage. The use of natural ingredients, one of which is garlic (Allium sativum L) in the form of boiled water, because it contains flavonoid and organosulfur compounds. Therefore, the purpose of this study was to determine the histology of the liver of mice (Mus musculus) induced by alloxan after being given a decoction of garlic (Allium sativum L). This study used experimental research with a completely randomized design method on mice consisting of 6 groups with 4 replications each. The groups in this study consisted of a negative control group (without treatment), a positive control group (alloxan injection) a comparison control group (alloxan injection + glibenclamide) treatment groups at doses I, II and III (alloxan-induced + garlic boiled water (Allium sativum L) respectively 20 gr, 40 gr and 60 gr). Histology of the liver of mice (Mus musculus) was made by paraffin method with Hematoxylin Eosin (HE) staining. The result showed that there was a significant difference due to the value (p&lt;0,05) but for a KP and P3 there was no significant difference with the value (p&gt;0,05) on hydropic degeneration. Based on the results of the study, it can be concluded that the decoction of garlic (Allium sativum L) has an effect on the alloxan-induced liver histology of mice (Mus musculus).