Elevated Malondialdehyde Levels Research Articles

Effects of microplastics on reproductive characteristics and mechanisms of the marine rotifer Brachionus plicatilis

Microplastic pollution, especially secondary microplastics (MPs), poses a significant threat to marine ecosystems. Despite its prevalence, the impact of natural-aged MPs on marine organisms, hindered by collection challenges, remains poorly understood. This study focused on 1–3 μm natural-aged MPs collected from Japan's coastal sea, investigating their effects on the rotifer Brachionus plicatilis sensu stricto and its reproductive mechanisms. Rotifers exposed to varying MP concentrations (0, 20, and 200 particles/mL) over 14-day batch cultures exhibited reduced population growth and fertilization rates. Down-regulation of reproductive genes and up-regulation of oxidative stress-related genes were observed, indicating MP-induced disruptions. Enhanced activities of superoxide dismutase and acetylcholinesterase and elevated malondialdehyde levels further emphasized oxidative stress. These findings underscore the detrimental impact of MPs on rotifer reproductivity, shedding light on the underlying mechanisms.

Diminazene aceturate inhibits the SARS-CoV-2 spike protein-induced inflammation involving leukocyte migration and DNA extracellular traps formation

AimsTo investigate the SARS-CoV-2 Spike protein (Spk)-induced inflammatory response and its downmodulation by diminazene aceturate (DIZE). Materials and methodsThrough inducing Spk inflammation in murine models, leukocyte migration to the peritoneum, levels of myeloperoxidase (MPO), malondialdehyde (MDA), rolling and adhesion of mesenteric leukocytes, and vascular permeability were investigated. Extracellular DNA traps (DETs) induced by Spk and the production of IL-6 and TNF-α were analyzed using human neutrophils, monocytes, and macrophages. In silico assays assessed the molecular interaction between DIZE and molecules related to leukocyte migration and DETs induction. Key findingsSpk triggered acute inflammation, demonstrated by increasing leukocyte migration. Oxidative stress was evidenced by elevated levels of MPO and MDA in the peritoneal liquid. DIZE attenuated cell migration, rolling, and leukocyte adhesion, improved vascular barrier function, mitigated DETs, and reduced the production of Spk-induced pro-inflammatory cytokines. Computational studies supported our findings, showing the molecular interaction of DIZE with targets such as β2 integrin, PI3K, and PAD2 due to its intermolecular coupling. SignificanceOur results outline a novel role of DIZE as a potential therapeutic agent for mitigating Spk-induced inflammation.

EFFECT OF PAXHERBAL BITTERS ON INFLAMMATION AND ANTIOXIDANT STATUS IN MALE WISTAR RATS FED A HIGH FRUCTOSE DIET

Modern diets are often high in fructose, and this has been associated with increased inflammation and oxidative stress. Herbal remedies like Paxherbal bitters have been suggested as possible remedies. This study aims at determining if the co-administration of Paxherbal bitters could prevent the inflammation and oxidative stress, which occurs when male Wistar rats are fed a high fructose diet. Twenty male Wistar rats, approximately 200g each, were divided into four groups: the control, high fructose diet with fructose water (HFD+FW), HFD+FW with Atorvastatin, and HFD+FW with Paxherbal bitters, groups. After a 28-day experimental period, blood samples were assessed for high-sensitive C-reactive protein (HsCRP), malondialdehyde (MDA), and total antioxidant capacity (TAC), using standard methods. Statistical analysis was done using the SPSS-20 package. Results has shown that rats on the high fructose diet, displayed significantly (P<0.05) elevated HsCRP (0.63±0.04 mg/dl) and MDA (0.32±0.01 µM) levels, compared to control levels (0.27±0.01 mg/dl; 0.10±0.01 µM). Both Atorvastatin and Paxherbal bitters significantly (P<0.05) prevented the elevation of HsCRP, while only Paxherbal bitters significantly (P<0.05) prevented the increase in MDA level (0.13±0.02 µM) compared to the level seen in the HFD+FW group. The high fructose diet significantly (P<0.05) reduced the TAC in the rats, but Atorvastatin and Paxherbal bitters preserved the TAC (0.38±0.03 µmol/ml; 0.49±0.04 µmol/ml) of their respective groups compared to that of the negative control group (0.21±0.06 µmol/ml). This study shows that Paxherbal bitters prevented the inflammation and oxidative stress induced by a high fructose intake, suggesting its co-administration, has some preventive therapeutic role.

Elucidation of the Possible Molecular Mechanism for the Anti-Apoptotic Ef-fect of Terpene-Rich Extract of Amomum subulatum and Coriandrum sa-tivum against Rodent Model of Cardiotoxicity

Background: Spices, including Amomum subulatum and Coriander sativum, are not only popular for improving food flavour but are also accepted worldwide for their health benefits in various disorders. background: Spices including Amomim subulatum and Coriander sativum are not only popular to improve food flavour but also worldwide accepted for their health benefits in various disorders to preventive and curative importance. Objective: This study aimed to elucidate the possible mechanism for the anti-apoptotic effect of terpene-rich extract of Amomum subulatum and Coriandrum sativum against the rodent model of cardiotoxicity. Methods: Effects of standardized terpenoids-rich aqueous methanolic extract of two commonly used spices, viz. Amomum subulatum Roxb. and Coriandrum sativum Linn., were investigated on doxorubicin-induced apoptotic changes and cardiotoxicity in Wistar rats with the aim of in-vestigating the mechanism. Prior to the in vivo experiment, the extracts were subjected to quan-titative estimation of possible bioactive markers of the terpenes by employing a newly devel-oped, optimized, and validated GC-MS method along with TLC profiling. Results: Cardiotoxicity was evident from elevated creatinine kinase (CK-MB), lactate dehydro-genase (LDH), and malondialdehyde (MDA) levels in the toxic control group after treatment with doxorubicin (2.5mg/kg i.p. given twice a week for three weeks). Caspase-3, Tumor necrosis factor-α (TNF-α), and Interleukin-6 (IL-6) were also induced in animals treated with doxorubi-cin. Treatment with Amomum subulatum and Coriandrum sativum at the doses of 100 and 200mg/kg exhibited significant (P<0.001) reversal of CK-MB, LDH, MDA, Caspase-3, TNF-α, and IL-6 levels. This protective effect was further supported by the results of DNA gel electro-phoresis and histopathological observations. Conclusion: This study supports the cardioprotective role of selected spices against doxorubicin-induced cardiotoxicity through the anti-apoptotic mechanism.

Copper-Nanoparticle-Induced Neurotoxic Effect and Oxidative Stress in the Early Developmental Stage of Zebrafish (Danio rerio).

Copper nanoparticles (CuNPs) are extensively used in electronics, cosmetics, fungicides, and various other fields due to their distinctive qualities. However, this widespread usage can contribute to environmental contamination and heightened health risks for living organisms. Despite their prevalent use, the ecological impacts and biosafety of CuNPs remain inadequately understood. The present study aims to delve into the potential toxic effects of CuNPs on zebrafish (Danio rerio) embryos, focusing on multiple indexes such as embryonic development, neurotoxicity, oxidative stress, and inflammatory response. The results revealed a notable increase in the death rate and deformity rate, alongside varying degrees of decrease in hatching rate and heart rate following CuNPs exposure. Particularly, the frequency of spontaneous tail coiling significantly declined under exposure to CuNPs at concentrations of 500 µg/L. Furthermore, CuNPs exposure induced alterations in the transcriptional expression of GABA signaling pathway-related genes (gabra1, gad, abat, and gat1), indicating potential impacts on GABA synthesis, release, catabolism, recovery, and receptor binding. Additionally, CuNPs triggered oxidative stress, evidenced by disruption in superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, along with elevated malondialdehyde (MDA) levels. This oxidative stress subsequently led to a proinflammatory cascade, as demonstrated by the increased transcriptional expression of inflammatory markers (il-1β, tnf-α, il-6, and il-8). Comparative analysis with copper ion (provided as CuCl2) exposure highlighted more significant changes in most indexes with CuCl2, indicating greater toxicity compared to CuNPs at equivalent concentrations. In conclusion, these findings provide valuable insights into the toxic effects of CuNPs on zebrafish embryo development and neurotransmitter conduction. Furthermore, they present technical methodologies for assessing environmental and health risks associated with CuNPs, contributing to a better understanding of their biosafety and ecological impact.

Investigating the Role of Oxidant-Antioxidant Balance in the Etiology of Migraine

Aim: Migraine, a prevalent neurovascular disorder, is marked by repetitive headache episodes. Its complex etiology encompasses biochemical, genetic, and environmental influences, but its exact pathophysiology remains elusive. Recent studies have hinted at a link between migraine and oxidative stress. Hence, this study sought to delve into the correlation between migraine, oxidative stress markers, and lipid profiles. Material and Method: This case-control study involved 60 adult migraine patients from Dicle University's Neurology Department in Diyarbakır, Türkiye, observed between 2009 and 2010. The control group was age- and gender-matched healthy individuals. Parameters like malondialdehyde (MDA), paraoxonase-1 (PON-1), total antioxidant capacity (TAC), and lipid constituents such as total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were measured in both groups. Results: Migraine sufferers, particularly those with aura, had significantly elevated MDA levels compared to controls (p

Regulatory Mechanism through Which Old Soybean Leaves Respond to Mn Toxicity Stress.

Manganese (Mn) is a heavy metal that can cause excessive Mn poisoning in plants, disrupting microstructural homeostasis and impairing growth and development. However, the specific response mechanisms of leaves to Mn poisoning have not been fully elucidated. This study revealed that Mn poisoning of soybean plants resulted in yellowing of old leaves. Physiological assessments of these old leaves revealed significant increases in the antioxidant enzymes activities (peroxidase (POD), superoxide dismutase (SOD), ascorbate peroxidase (APX), and catalase (CAT)) and elevated levels of malondialdehyde (MDA), proline, indoleacetic acid (IAA), and salicylic acid (SA), under 100 μM Mn toxicity. Conversely, the levels of abscisic acid (ABA), gibberellin 3 (GA3), and jasmonic acid (JA) significantly decreased. The Mn content in the affected leaves significantly increased, while the levels of Ca, Na, K, and Cu decreased. Transcriptome analysis revealed 2258 differentially expressed genes in the Mn-stressed leaves, 744 of which were upregulated and 1514 were downregulated; these genes included genes associated with ion transporters, hormone synthesis, and various enzymes. Quantitative RT-PCR (qRT-PCR) verification of fifteen genes confirmed altered gene expression in the Mn-stressed leaves. These findings suggest a complex gene regulatory mechanism under Mn toxicity and stress, providing a foundation for further exploration of Mn tolerance-related gene regulatory mechanisms in soybean leaves. Using the methods described above, this study will investigate the molecular mechanism of old soybean leaves' response to Mn poisoning, identify key genes that play regulatory roles in Mn toxicity stress, and lay the groundwork for cultivating high-quality soybean varieties with Mn toxicity tolerance traits.

Superoxide Dismutase Modified the Association of Serum Malondialdehyde Levels with Cognitive Decline Among Older Adults: Findings from the Chinese Longitudinal Healthy Longevity Survey.

Numerous studies have investigated the correlation between malondialdehyde (MDA) and cognitive decline. However, limited research has explored the interplay between superoxide dismutase (SOD), C-reactive protein (CRP), and MDA. This study aims to scrutinize the association between MDA and cognitive function in older adults, while also elucidating the roles of SOD and CRP within this relationship. Utilizing data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) spanning 2008-2009, 2011-2012, and 2014, this study included 2,696 eligible subjects. Cognitive function was evaluated using the Chinese version of the Mini-Mental State Examination (MMSE). Linear mixed-effects models were employed to examine the links between MDA, SOD, CRP, and their interactions with cognitive function. Elevated serum levels of MDA and CRP, as well as decreased serum SOD levels, were related to decreased cognitive function (β= -0.220 and -0.346, 95% CI: -0.399, -0.041 and -0.526, -0.167 for MDA and CRP; β= 0.384, 95% CI: 0.204, 0.564 for SOD). Notably, a significant interaction between MDA and SOD was detected (p = 0.001). An increase per standard deviation in serum MDA levels was significantly associated with a 0.347-point lower MMSE score only in participants with normal cognitive function and high SOD levels (β= -0.347, 95% CI: -0.497, -0.197; p < 0.001). Elevated serum MDA levels in the normal population with high SOD levels suggested diminished cognitive performance. Combining MDA with SOD could be pivotal in identifying older adults at risk of cognitive decline in clinical settings.

Evaluation of antioxidant enzyme levels, oxidative stress markers and serum prolidase activity in testicular cancer.

Testicular cancer is a significant malignancy affecting males, and understanding the underlying biochemical changes associated with the disease is essential for improved management and treatment strategies. Prolidase enzyme, has been implicated in various disease processes. The assessment of serum prolidase activity and its relationship with testicular cancer can provide valuable insights into the pathophysiology of the disease. The objective of this study was to investigate serum prolidase activity, oxidative stress markers, and antioxidant enzyme levels in patients with testicular cancer and evaluate their potential associations, aiming to enhance our understanding of the biochemical alterations and potential implications for testicular cancer management. A total of 33 male patients diagnosed with testicular cancer were included, along with 35 age-matched male volunteers as the control group. Serum samples were collected and stored at -20°C until analysis. The measurement of superoxide dismutase (SOD), glutathione peroxidase (GSHPx), glutathione-S-transferase (GST), malondialdehyde (MDA), glutathione (GSH), and prolidase levels was performed. The findings demonstrated significantly elevated serum prolidase activity and malondialdehyde (MDA) levels in testicular cancer patients compared to the control group (all, p < 0.05). Conversely, superoxide dismutase (SOD), glutathione peroxidase (GSHPx), and glutathione-S-transferase (GST) levels were significantly lower in testicular cancer patients (p < 0.05). In this study, serum prolidase activity and biochemical markers associated with oxidative stress were investigated in testicular cancer patients. Oxidative stress markers and serum prolidase activity were found to be elevated in testicular cancer. Long-term prospective studies are needed to determine the effectiveness of antioxidant use in cancer treatment.

Exploring the impact of organic and inorganic amendments, with foliar application of iron nanoparticles, on cadmium stabilization and growth of maize in wastewater irrigated-soil

ObjectivesThis study addresses the critical issue of Cd contamination in agricultural soils, posing substantial risks to crop productivity and food safety. While prior pot experiment has undertook this issue on a small scale, this study aims to evaluate the efficacy of selected best soil amendments, at a large-scale field experiment. MethodologyPress mud and humic acid were applied at 0.5%, while gypsum and Fe2O3 were applied at 5 mg/kg alone and with foliar application of Fe nanoparticles at 5 mg/L. AnalysisComparative analysis with control revealed the immobilization efficiency of all amendments in descending order of effectiveness as follows: 100, 102, 104, 104, 105, 102, 105, and 105% for PM, HA, GYP, Fe, PM + Fe Nps, HA + Fe Nps, GYP + Fe Nps, and Fe + Fe Nps. Additionally, reduced growth, photosynthetic activities, and elevated levels of malondialdehyde and hydrogen peroxide, indicative of oxidative damage in control plant. FindingsApplication of these amendments with foliar spraying of Fe Nps effectively mitigates Cd toxicity in maize crops, leading to improved growth, biomass, photosynthetic pigments, and antioxidant enzyme activities. Novelty/ImprovementThese findings highlight the significance of exploring innovative approach of combining different amendments with foliar application of nanoparticles to mitigate Cd contamination and enhance soil health, thereby contributing to global efforts in ensuring food safety and security.

Utilizing chitosan and titanium dioxide nanomaterials and their nanocomposites for improving the growth and biochemical responses of Sorghum bicolor (L.)

It is imperative to comprehensively assess the impact of nano-based technologies on plants and ensure their safety before integrating them into agricultural practices. In this context, the present study demonstrates the effect of nanosized chitosan (CS), titanium dioxide (TiO2), and CS/TiO2 nanocomposites (NCPs) on Sorghum bicolor (L.) Moench, the fifth most important grain crop globally. The nanomaterials were chemically synthesized and characterized in terms of size, surface morphology, structure, functional groups, and hydrodynamic diameter. S. bicolor plants were cultivated in soil spiked with these nanomaterials at two different concentrations (100 and 200 ppm) for up to 30 days. Compared to control plants, all three nanomaterials stimulated the growth of S. bicolor by 3-23% and enhancednutrient uptake. Additionally, they increased the concentrations of chlorophyll (35-94%), starch (13-19%), cellulose (12-56%), and protein (3-119%) in the shoots, while reducing the malondialdehyde (MDA) content. However, elevated MDA levels in the roots of plants treated with TiO2 nanoparticles and CS/TiO2 NCPs indicated that mild oxidative stress had occurred, which the plant managed to counteract by enhancing antioxidant enzyme activities. The findings of this study confirm the safety of using these nanomaterials and provide a foundation for future research aimed at enhancing the growth, adaptability, and yield of S. bicolor.

Effect of Sodium Fluoride on Oxidative Stress and Antioxidant System in Male Wistar Rats

This research aimed to examine the effect of sodium fluoride (NaF) on oxidative stress and antioxidant systems in the serum, aorta, and cardiac tissues of male Wistar rats. The increased attention to sodium fluoride and its detrimental effects on human health in recent years has led to concerns. Excessive ingestion and accumulation of sodium fluoride from water, toothpaste, and pesticides could initiate oxidative stress in the blood, aorta, and heart. This heightened oxidative stress and disturbance in the antioxidant system pose a significant risk and may predispose the body to severe vascular and cardiovascular-related diseases, which are leading causes of global mortality. In this study, ten male Wistar rats weighing 150-180g were grouped into two (n=5). Group I Control received distilled water, and Group 2 received 10mg/kg NaF orally for 21 days. Markers of oxidative stress malondialdehyde (MDA) and reduced glutathione (GSH), antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and total antioxidant capacity (TAC) were measured in the serum, aorta, and heart. Data were analyzed using descriptive statistics of student t-test at α0.05. The data were presented as mean ± SEM. The oral administration of sodium fluoride resulted in an elevation of MDA levels in the serum, aorta, and heart of the rats exposed to NaF. Additionally, the oral administration of sodium fluoride led to a reduction in superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) levels in the serum, aorta, and heart of rats exposed to NaF. Furthermore, the oral administration of sodium fluoride resulted in a decrease in the total antioxidant capacity (TAC) in the serum, aorta, and heart of rats exposed to sodium fluoride. This study demonstrated that sodium fluoride exposure diminishes the antioxidant capacity in the serum, aorta, and heart, indicating that sodium fluoride exposure induces oxidative stress, potentially affecting the functions of the aorta and heart. Therefore, the continuous exposure to fluoride in populations residing in regions with endemic fluorosis worldwide should be a topic of considerable concern. This research work was self-funded. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Oxidative Stress Markers Evaluation after Prolonged Administration of Aqueous Extract of Raphia Hookeri Fruit Pulp in Male Wistar Rats

The study investigated effect of prolonged administration of Raphia Hookeri fruit pulp on oxidative stress markers in male wistar rats. A total of 24 male wistar rats of weight ranging from 200g to 350g were used. The rats divided in 4 groups, 3 groups administered orally with doses of extract at 500mg/kg, 1000mg/kg and 2000mg/kg body weight while control group fed with feed and water for 28 days. The animals sacrificed, samples taken, laboratory test done for stress markers. Statistical analysis done at p&lt;0.05, values expressed as SEM. Results showed Malondialdehyde (MDA) values for group 2(0.77 ± 0.32nm/ml), group 3(1.79 ± 0.73nm/ml) and group 4(3.35 ± 0.20nm/ml) while for group 1(Control group) MDA value is 4.10 ± 0.3nm/ml. Mean values for Superoxide Dismutase (SOD) in treated groups (2-4) were 18.00 ± 1.0 units/ml, 29.50 ± 8.50units/ml, and 33.50 ± 37.25units/ml respectively and mean value for control group was 68.00 ± 4.0units/ml. Mean values for Glutathione Peroxidase (GPx) in test groups (2-4) were 53.50 ± 10.50ng/ml, 63.50 ± 5.50ng/ml, and 82.50 ± 6.50ng/ml respectively. GPx value for control group was 94.00 ± 3.00ng/ml. There was a graded increase from low dose to high dose. All treated groups indicated marginally (P&gt;0.05) reduced values of Percentage change in body weight when compared to the control group (Group 1). Elevated levels of MDA indicates an increased oxidative stress and lipid. Higher levels of SOD and Gpx. This research demonstrates the ability of Raphia Hookeri fruit pulp to decrease oxidative stress hence regular consumption is recommended.

Preventive effects of lactoferrin on acute alcohol-induced liver injury via iron chelation and regulation of iron metabolism

Lactoferrin is widely found in milk and has the ability to bind iron. Previous studies have reported that lactoferrin was effective in the prevention and treatment of acute alcohol-induced liver injury (AALI). Ferroptosis is a recently discovered cell death and is involved in the development of AALI. However, the potential role of lactoferrin in acute alcohol-induced ferroptosis is still unclear. In this study, we observed that lactoferrin (10, 20 and 40 μg/mL) significantly mitigated alcohol (300 mM)-induced injury in vitro. Additionally, lactoferrin (100 and 200 mg/kg bw) significantly alleviated alcohol (4.8 g/kg bw)-induced injury in vivo. Our results showed that lactoferrin inhibited alcohol-induced upregulation of the ferroptosis marker protein ACSL4 and downregulation of GPX4. Meanwhile, lactoferrin treatment successfully reversed the elevated Malondialdehyde (MDA) levels and the reduced Glutathione (GSH) levels caused by alcohol treatment. These results can indicate that lactoferrin significantly decreased ferroptosis in vivo and in vitro. Lactoferrin has the potential to chelate iron, and our results showed that lactoferrin (20 μg/mL) significantly reduced iron ions and the expression of Ferritin Heavy Chain (FTH) under FeCl3 (100 μM) treatment. It was demonstrated that lactoferrin had a significant iron-chelating effect and reduced iron overload caused by FeCl3 in AML12 cells. Next, we examined iron content and the expression of iron metabolism marker proteins Transferrin Receptor (TFR), Divalent metal transporter 1 (DMT1), FTH, and Ferroportin (FPN). Our results showed that lactoferrin alleviated iron overload induced by acute alcohol. The expression of TFR and DMT1 was downregulated and FPN and FTH were upregulated after lactoferrin treatment in vivo and in vitro. Above all, the study suggested that lactoferrin can alleviate AALI by mitigating acute alcohol-induced ferroptosis. Lactoferrin may offer new strategies for the prevention or treatment of AALI.

Esculin induces endoplasmic reticulum stress and drives apoptosis and ferroptosis in colorectal cancer via PERK regulating eIF2α/CHOP and Nrf2/HO-1 cascades

Ethnopharmacological relevanceCortex fraxini (also known as Qinpi), the bark of Fraxinus rhynchophylla Hance and Fraxinus stylosa Lingelsh, constitutes a crucial component in several traditional Chinese formulas (e.g., Baitouweng Tang, Jinxiao Formula, etc.) and has demonstrated efficacy in alleviating intestinal carbuncle and managing diarrhea. Cortex fraxini has demonstrated commendable anticancer activity in the realm of Chinese ethnopharmacology; nevertheless, the underlying mechanisms against colorectal cancer (CRC) remain elusive. Aim of the studyEsculin, an essential bioactive compound derived from cortex fraxini, has recently garnered attention for its ability to impede viability and induce apoptosis in cancer cells. This investigation aims to assess the therapeutic potential of esculin in treating CRC and elucidate the underlying mechanisms. Materials and methodsThe impact of esculin on CRC cell viability was assessed using CCK-8 assay, Annexin V/PI staining, and Western blotting. Various cell death inhibitors, along with DCFH-DA, ELISA, biochemical analysis, and Western blotting, were employed to delineate the modes through which esculin induces HCT116 cells death. Inhibitors and siRNA knockdown were utilized to analyze the signaling pathways influenced by esculin. Additionally, an azomethane/dextran sulfate sodium (AOM/DSS)-induced in vivo CRC mouse model was employed to validate esculin's potential in inhibiting tumorigenesis and to elucidate its underlying mechanisms. ResultsEsculin significantly suppressed the viability of various CRC cell lines, particularly HCT116 cells. Investigation with diverse cell death inhibitors revealed that esculin-induced cell death was associated with both apoptosis and ferroptosis. Furthermore, esculin treatment triggered cellular lipid peroxidation, as evidenced by elevated levels of malondialdehyde (MDA) and decreased levels of glutathione (GSH), indicative of its propensity to induce ferroptosis in HCT116 cells. Enhanced protein levels of protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) and p-eIF2α suggested that esculin induced cellular endoplasmic reticulum (ER) stress, subsequently activating the Nrf2/ARE signaling pathway and initiating the transcriptional expression of heme oxygenase (HO)-1. Esculin-induced excessive expression of HO-1 could potentially lead to iron overload in HCT116 cells. Knockdown of Ho-1 significantly attenuated esculin-induced ferroptosis, underscoring HO-1 as a critical mediator of esculin-induced ferroptosis in HCT116 cells. Furthermore, utilizing an AOM/DSS-induced colorectal cancer mouse model, we validated that esculin potentially inhibits the onset and progression of colon cancer by inducing apoptosis and ferroptosis in vivo. ConclusionsThese findings provide comprehensive insights into the dual induction of apoptosis and ferroptosis in HCT116 cells by esculin. The activation of the PERK signaling pathway, along with modulation of downstream eIF2α/CHOP and Nrf2/HO-1 cascades, underscores the mechanistic basis supporting the clinical application of esculin on CRC treatment.

Renal Fibrosis and Oxidative Stress Induced by Silica Nanoparticles in Male Rats and Its Molecular Mechanisms.

The utilization of amorphous silica nanoparticles (SiNPs) is gaining popularity in various applications, but it poses a potential risk to human and environmental health. However, the underlying causes and mechanisms of SiNPs-induced kidney damage are still largely unknown. This study aimed to investigate the SiNPs-induced damage in the kidney and further explore the possible mechanisms of SiNPs-induced nephrotoxicity. Thirty adult male rats were divided into 3 different groups. Rats in groups 2 and 3 were administered SiNPs at 2 dosage levels (25 and 100 mg/kg of body weight), while the rats in the control group received no treatment for 28 days. Reactive oxygen species (ROS), antioxidant enzyme activities (glutathione peroxidase [GPx], superoxide dismutase [SOD], and catalase [CAT]), glutathione (GSH) levels, and oxidation markers (such as lipid peroxidation [malondialdehyde (MDA)] and protein oxidation [protein carbonyl (PCO)]) were analyzed in the kidney tissue. Additionally, renal fibrogenesis was studied through histopathological examination and the expression levels of fibrotic biomarkers. The findings revealed that in vivo treatment with SiNPs significantly triggered oxidative stress in kidney tissues in a dose-dependent manner. This was characterized by increased production of ROS, elevated levels of MDA, PCO, and nitric oxide (NO), along with a significant decline in the activities of SOD, CAT, GPx, and reduced GSH. These changes were consistent with the histopathological analysis, which indicated interstitial fibrosis with mononuclear inflammatory cell aggregation, tubular degeneration, glomerulonephritis, and glomerular atrophy. The fibrosis index was confirmed using Masson's trichrome staining. Additionally, there was a significant upregulation of fibrosis-related genes, including transforming growth factor-beta 1 (TGF-β1), matrix metalloproteinases 2 and 9 (MMP-2/9), whereas the expression of tissue inhibitor of metalloproteinase 2 (TIMP2) was downregulated. This study provided a new research clue for the role of ROS and deregulated TGF-β signaling pathway in SiNPs nephrotoxicity.

Стрессорное воздействие биоцидных метаболитов актинобактерии Streptomyces geldanamycininus Z374 на цианобактерии Microcystis aeruginosa

Over the past decades, as a result of anthropogenic pollution and global warming, the frequency, intensity and geographical distribution of the mass development of microalgae and cyanobacteria in water bodies have significantly increased. The Microcystis species are responsible for most cases of the cyanobacterial blooms in freshwater bodies worldwide. Microcystis aeruginosa is the most commonly observed of them. In this work, we assessed the stress effect of isolated from actinobacteria Streptomyces geldanamycininus cyanocidal crude biocide Z374 (CB Z374) on the cyanobacteria M. aeruginosa. The results showed that CB Z374 significantly inhibited M. aeruginosa biomass. The CB Z374 half maximal effective concentration (EC50) for M. aeruginosa after 96 hours of treatment was 5 mg/L. The growth of M. aeruginosa with CB Z374 is characterized by an increase in the duration of the lag-phase, a decrease in the specific growth rate and biomass yield compared to the control. CB Z374 caused oxidative stress in cyanobacteria cells, determined by the elevated levels of hydrogen peroxide (H2O2) and malondialdehyde (MDA) up to 1.6 times, as well as an increased permeability of M. aeruginosa cell membranes by 1.5 times. The levels of superoxide dismutase (SOD) and catalase (CAT) activities and reduced glutathione (GSH) content raised in response to oxidative stress. M. aeruginosa growth inhibition was accompanied by a photosynthesis modification: the photosynthetic pigments phycobiliproteins and carotenoids content increases by 2.3 and 1.6 times respectively and the chlorophyll a content decreases by 1.2 times. CB Z374 inhibited M. aeruginosa photosynthesis, which was expressed in a decline in the maximum quantum efficiency of photosystem II – Fv/Fm by 10% and a reduction in the electron transfer rate (ETR) by 18%. We assume that oxidative stress and, as a result, cell membranes damage and photosynthesis inhibition are the main mechanisms of the cyanocidal action of CB Z374 on M. aeruginosa.

The protective effects of Irbesartan in cognitive impairment in hypertension.

Vascular cognitive impairment (VCI) is claimed as the second most common type of dementia after Alzheimer's disease (AD), in which hypertension is a critical inducer. Currently, hypertension-induced cognitive impairment lacks clinical treatments. Irbesartan is a long-acting angiotensin receptor antagonist with promising antihypertensive properties. Our research will focus on the potential function of Irbesartan on hypertension-induced cognitive impairment. Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats were orally dosed with normal saline or 20 mg/kg/day Irbesartan for 14 consecutive days, with 4 groups divided shown as below: WKY, Irbesartan, SHR, SHR+ Irbesartan. Firstly, the markedly increased systolic blood pressure observed in SHR rats was signally repressed by Irbesartan on Day 7 and 14 post-dosing. Moreover, notably decreased time of exploring the novel object in the object recognition task (ORT) test, elevated escape latency, and reduced time in the target quadrant in the Morris water maze (MWM) test were observed in SHR rats, which were prominently reversed by Irbesartan. Furthermore, the declined superoxide dismutase (SOD) activity, elevated malondialdehyde (MDA) level, increased cyclin-dependent kinase-5 (CDK5) activity, and enhanced protein level of p35/p25, p-Tau (pSer214)/Tau46, and brain-derived neurotrophic factor (BDNF) were memorably rescued by Irbesartan. Lastly, the activity of cAMP/cAMP response element binding protein (CREB) signaling in the hippocampus of SHR rats was markedly repressed, accompanied by an upregulation of phosphodiesterase 4B (PDE4B), which was observably rescued by Irbesartan. Collectively, Irbesartan protected against the hypertension-induced cognitive impairment in SHR rats by regulating the cAMP/CREB signaling.

Effects of Ethyl Acetate Fraction of Mangifera haden Seeds on Carbon Tetrachloride Induced Hepatotoxicity in Albino Rats

The present study investigated the effects of ethyl acetate fraction of Mangifera haden seeds on carbon tetrachloride-induced liver damage in wistar albino rats. The phytochemical compositions and acute toxicity studies of crude extract and Mangifera haden seed fraction were determined using standard methods. Albino rats (60) randomly grouped into twelve of five rats each were used for this study. Determination of total bilirubin and protein, lipid peroxidation, liver enzymes marker, antioxidant enzymes, glutathione, lipid profile analysis and histological examination were carried out using standard methods. Phytochemical constituents of crude extract and ethyl acetate fraction of Mangifera haden seed showed that they contain relative amount of flavonoids, phenolics, saponins, tannins, terpenoids, triterpenes, alkaloids and coumarins. Liver injury was induced with carbon tetrachloride (CCl4) at a dose of 1.0 ml/kg body weight of the animals. All the CCl4 intoxicated rats displayed hyperlipidemia as shown by their elevated levels of serum total cholesterol (TC), triacylglycerol (TAG), low density lipoprotein (LDL), and reduction in high density lipoprotein (HDL) levels. The administration of ethyl acetate fraction of Mangifera haden seeds significantly (P = 0.05) lowered the levels of serum TC, TAG, LDL, and increased HDL levels. The level of serum malondialdehyde (MDA) significantly (P = 0.05) increased in the CCl4 group as compared to the normal and treated groups. The elevated level of serum MDA decreased (P = 0.05) significantly at the treatment of rats with 200, 400 and 600 mg/kg of ethyl acetate fraction. The rats treated with CCl4 produced significant (P = 0.05) increase in serum ALT, AST and ALP when compared to the normal group. Animals treated with varying doses of ethyl acetate fraction produced significant (P = 0.05) reduction of serum ALT, AST and ALP activities when compared to the CCl4-untreated group. The activities of hepatic antioxidant enzymes (SOD, CAT and GPx) and glutathione concentration significantly (P = 0.05) decreased in CCl4­-untreated group compared to the normal group. The decreased activities of the antioxidant enzymes and glutathione concentration in CCl4 intoxicated rats were ameliorated/modulated more effectively in rats treated with 200, 400 and 600 mg/kg ethyl acetate fraction of Mangifera haden seed. Total bilirubin (TB) concentrations significantly (P = 0.05) increased in CCl4-untreated group when compared to the normal group. Oral treatment of rats with varying doses (200, 400, 600 mg/kg) of ethyl acetate fraction caused a significant (P = 0.05) decrease in the serum TB levels. Administration of CCl4 showed a reduction in serum total proteins. Treatment of the animals with 200, 400 and 600 mg/kg of ethyl acetate fraction caused significant (P = 0.05) increase in serum total potein. Histological examination showed hepatoprotective properties of plant’s fractions. The compounds found in the different fractions (ethyl acetate and n-hexane) of Mangifera haden seeds are 9-Octadecenoic acid (Z)-, methyl ester, (Z) –Oleic acid and so on. Therefore the medicinal importance of the plant is been established.

Post-traumatic Stress Disorder: The Influence of the Environmental Context and Analysis of Oxidative Stress and Inflammatory and Glycemic Markers in Women Living in Kurdistan Regional Government-Iraq.

Background Internally displaced persons (IDP) camps are still home to a large number of female survivors of the Yazidi genocide carried out in Iraq in 2014 by the Islamic organization known as the Islamic State of Iraq and Syria (ISIS). Many of these women suffer from a persistent form of post-traumatic stress disorder (PTSD), which can last for many years. On the other hand, little is known about the intricate etiology of PTSD. Objectives In this observational cross-sectional study, the biochemical parameters, including inflammatory and oxidative stress (OXS) markers, were evaluated in two groups: the case group (women with newly diagnosed PTSD) and the control group (apparently healthy women). Furthermore, how the environment impacts the biochemical and OXS parameters of people not diagnosed with PTSD but living in IDP camps was also analyzed. Materials and methods The PTSD group (n=55, age=30.0 years) was made up of women survivors of genocide-related events living in IDP camps in the Kurdistan region of Iraq. The studied parameters in the PTSD group have been compared to two healthy control groups: (1) internal control group (n=55, age=28.1 years): healthy women living inside the IDP camps; and (2) external control group (n=55, age=28.3 years): healthy women living outside the IDP camps. The diagnosis of PTSD was conducted using a validated Kurdish version of the PTSD Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (PCL-5) scale. Blood samples were collected to determine the level of glycated hemoglobin (HbA1c) and the concentrations of fasting serum glucose (FSG), C-reactive protein (CRP), ceruloplasmin (CP), 8-hydroxydeoxyguanosine (8-OHdG), glutathione (GSH), malondialdehyde (MDA), protein carbonyls (PC), and catalase (CAT) activity. Results Women with PTSD presented increased values of FSG (4.41%, p<0.05), HbA1c (4.74%, p<0.05), and CRP (114.29%, p<0.05), as well as increased levels of 8-OHdG (185.97%, p<0.001), CP (27.08%, p<0.001), MDA (141.97%, p<0.001), and PC (63.01%, p<0.001), besides increased CAT activity (121.5%, p<0.001), when compared with the control groups. A significant reduction of GSH (-20.33%, p<0.05) was observed in PTSD patients as compared to the external control group. In relation to the internal control group, women diagnosed with PTSD presented significantly increased levels of FSG (3.88%, p<0.05), HbA1c (2.83%, p<0.05), CRP (77.97%, p<0.05), and PC (41.3%, p<0.05), as well as increased levels of 8-OHdG (118.84%, p<0.001), CP (22.72%, p<0.001), MDA (90.67%, p<0.001), and CAT activity (55.31%, p<0.001). Healthy individuals residing in IDP camps, compared with external healthy control, presented significantly elevated levels of 8-OHdG (30.68%, p<0.001), MDA (26.91%, p<0.001), PC (15.37%, p<0.001), and CAT activity (42.62%, p<0.001). Conclusion Our findings indicate that PTSD significantly influences glycemic, inflammatory, oxidant, and antioxidant parameters, as evidenced by increased levels of FSG, HbA1C, CRP, PC, MDA, 8-OHdG, and CP, as well as increased CAT activity and a reduced GSH concentration in the PTSD group in comparison to the external control group. Additionally, our results suggest that the environmental context in IDP camps by itself can potentially affect oxidant and antioxidant parameters, as evidenced by the increased concentrations of 8-OHdG, MDA, and PC and increased CAT activity found in individuals not diagnosed with PTSD but living inside the camps.