Oxidative Stress Gene Expression Research Articles

Resistance of Pinus pinea to Bursaphelenchus xylophilus explained by the dynamic response of phytohormones, antioxidant activity, and stress-related gene expression

Key messageThe effects of MJ on pine trees are species-specific and trigger a resistant phenotype to the PWN. A more dynamic response of hormones and gene expression in Pinus pinea explains the high resistance to Bursaphelenchus xylophilus of this species.Knowledge on hormonal and genetic mechanisms of pine trees in response to the pinewood nematode (PWN; Bursaphelenchus xylophilus) is limited. To describe tree defence strategies against B. xylophilus, this study used the plant stress hormone methyl jasmonate (MJ) on four pine species with different susceptibility (Pinus pinaster < P. radiata ≈ P. sylvestris < P. pinea). Three-year-old trees were sprayed with MJ at 0, 25, and 50 mM, and 2 months later challenged with the PWN. Multiple samples were taken to assess nematode content, oxidative stress, secondary metabolites, phytohormone levels, and stress-related gene expression. Nematode infestation in trees correlated negatively with the water content of needles and phenolics of stems, and positively with the concentration of indole-3-carboxylic acid in stems. MJ spray reduced in a dose-dependent manner the nematode content in P. pinaster and P. sylvestris. The effects of MJ were species-specific, although a more pronounced impact was observed in the susceptible P. pinaster species, leading to a decrease of chlorophyll and water loss and to the upregulation of the gene involved in the biosynthesis of terpenoids (AFS). After MJ spray, increased levels of JA-Ile were observed in P. pinea only. Hormone profiling, predisposition to activate antioxidant response, and gene expression in P. pinea trees provide evidence of why this species is highly resistant to B. xylophilus. On the contrary, the lack of effective hormonal changes in P. pinaster explained the lack of defence responses to B. xylophilus of this susceptible species. This study is a first approach to explore biochemical, molecular, and hormonal interactions between Pinus species and the PWN, and presents unprecedented insights into alterations induced by exogenous MJ in regulating defence mechanisms in pine trees.

Salicylalazine: A novel therapeutic agent targeting TLR4/NLRP3/GSDMD-mediated pyroptosis in rheumatoid arthritis.

Joint pain and functional impairment are hallmarks of arthritis, a painful inflammatory disease. Salicylalazine (SAZ), an anti-inflammatory compound, has demonstrated promise in modulating inflammation, thereby being selected in the current study to unveil its anti-arthritic potential. The aim behind this study was to assess the anti-arthritic properties of salicylalazine via evaluating its impact on paw volume, arthritic scores, oxidative stress indicators, and significant inflammatory mediators. The arthritic potential of SAZ was estimated first through the formaldehyde (FA) model to screen the most effective dose of SAZ, followed by the Complete Freund's adjuvant (CFA) model. Over a 28-day period, we monitored parameters such as paw edema, arthritic index, body weight, flexion pain, mobility, and stance score. Oxidative stress markers (GSH, CAT, SOD, MDA), serological markers (CRP, RF, anti-CCP), and gene expression of key inflammatory mediators (TLR4, MyD88, NFκB, NLRP3, ASC, IL-1β, IL-18, caspase-1, GSDMD) were assessed. SAZ treatment led to a substantial decrease in paw volume in both arthritis models, with the most pronounced effects observed on day 10 for the formaldehyde model and day 28 for the CFA model (p<0.001). Additionally, SAZ helped to restore the body's weight and considerably relieved the flexion pain, which led to improvements in both mobility and stance. Moreover, SAZ substantially raised the levels of antioxidant enzymes (GSH, CAT, SOD) and decreased MDA levels, suggesting a reduction in oxidative stress. Also with SAZ, there was a substantial (p<0.001) decrease in the expression of pyroptotic mediators. Serological markers of inflammation, including CRP, RF, and anti-CCP levels, were also restored by SAZ administration. In a nutshell, SAZ achieved significant anti-arthritic benefits, most likely via the modulation of the TLR4/NLRP3/GSDMD-mediated pyroptosis pathway, lowering oxidative stress, and improvement of clinical findings. Taking into consideration these findings, it seems that SAZ has the potential to be an effective treatment alternative for the management of arthritis.

Impacts of Micro/Nanoplastics Combined with Graphene Oxide on Lactuca sativa Seeds: Insights into Seedling Growth, Oxidative Stress, and Antioxidant Gene Expression.

Global pollution caused by micro/nanoplastics (M/NPs) is threatening agro-ecosystems, compromising food security and human health. Also, the increasing use of graphene-family nanomaterials (GFNs) in agricultural products has led to their widespread presence in agricultural systems. However, there is a large gap in the literature on the combined effects of MNPs and GFNs on agricultural plants. This study was conducted to explore the individual and combined impacts of polystyrene microplastics (PSMPs, 1 μm) or nanoplastics (PSNPs, 50-100 nm), along with agriculturally relevant graphene oxide (GO), on the seed germination and seedling growth of lettuce (Lactuca sativa). The results showed that the combined effects of mixtures of PSMPs/PSNPs and GO exhibited both synergism and antagonism, depending on different toxicity indicators. The cellular mechanism underlying the combined effects on the roots and shoots of seedlings involved oxidative stress. Three SOD family genes, namely, Cu/Zn-SOD, Fe-SOD, and Mn-SOD, played an important role in regulating the antioxidant defense system of seedlings. The extent of their contribution to this regulation was associated with both the distinct plastic particle sizes and the specific tissue locations within the seedlings.

Quercetin and Mesenchymal Stem Cell Metabolism: A Comparative Analysis of Young and Senescent States.

Quercetin is a natural flavonoid renowned for its potent antioxidant, anti-inflammatory, anti-diabetic, and antibacterial properties, making it a highly promising candidate for the treatment of various medical conditions. Our current study investigates the influence of quercetin on energy metabolism, fatty acid composition, oxidative stress gene expression, and sirtuin expression in early- and late-stage passages of stem cells derived from human exfoliated deciduous teeth (SHEDs). Mitochondrial respiration was analyzed by measuring oxygen consumption following a 24 h quercetin treatment, while fatty acid profiles were examined using gas chromatography-mass spectrometry (GC-MS). Additionally, quantitative PCR (qPCR) was used to assess the expression of oxidative stress genes and sirtuins. In younger SHEDs, quercetin enhances metabolic activity and mitochondrial respiration, although higher doses may decrease mitochondrial activity. Conversely, in older, senescent SHEDs, quercetin supports mitochondrial function at lower concentrations but appears to inhibit respiration at higher doses. These results suggest that quercetin may hold therapeutic potential for maintaining SHED viability and function, especially at lower doses in older cells. Further research is essential to fully elucidate a dose-dependent effect of quercetin and optimize its applications in regenerative medicine.

Bushen Jianpi Tiaoxue Decoction (BJTD) ameliorates oxidative stress and apoptosis induced by uterus ageing through activation of the SIRT1/NRF2 pathway

BackgroundUterus ageing is a crucial factor contributing to decreased fertility in older women and is also implicated in menstrual disorders, endometritis, and adenomyosis. Bushen Jianpi Tiaoxue Decoction (BJTD) is a traditional Chinese medicine formulation used to ameliorate endocrine disorders in the female reproductive system and finds extensive application in ageing-related endometrial diseases. However, the mechanisms underlying its improvement of uterus ageing have not been thoroughly investigated. PurposeTo explore the potential components and mechanisms of BJTD in ameliorating uterus ageing through network pharmacology, in vivo, and in vitro experiments. MethodsMorphological changes were observed using hematoxylin and eosin staining, collagen deposition was assessed using Masson staining, and apoptotic-related molecules were detected using Western blot. After determining the modeling doses, BJTD intervention was administered at two doses, and the expression of oxidative stress and apoptosis-related genes and proteins was measured. The levels of cellular apoptosis were evaluated using the TUNEL assay kit and Annexin V/FITC-PI assay kit. The main components of BJTD were determined by UPLC-MS, and the potential targets and mechanisms of BJTD action were explored using network pharmacology and molecular docking. BJTD-Containing Serum (BJTD-S) was extracted and applied in vitro experiments using human endometrial stroma cells (hESC) to preliminarily identify the pathways affected. ResultsWe demonstrated that modeling with 600 mg/kg/day D-Gal for 5 weeks significantly increased collagen deposition in uterine tissues, particularly in the glands and stroma. Additionally, it significantly elevated the levels of TNF-α and IL-1β and increased the expression of p53 and BAX while decreasing BCL-2 expression. BJTD significantly reduced the increased levels of TNF-α and IL-1β induced by D-Gal, and modulated oxidative stress markers such as SOD, MDA, GSH-Px, and T-AOC. BJTD also inhibited the cascade activation of apoptosis induced by D-Gal, suppressing the expression of cleaved-Caspase 8, cleaved-Caspase 3, and BAX. SIRT1 is a potential target of BJTD action. In vitro experiments showed that BJTD-S significantly improved D-Gal-induced apoptosis in hESC cells, and the expression levels of SIRT1, NRF2, and HO-1 were significantly decreased in D-Gal-induced hESC, and BJTD-S significantly increased their expression. ConclusionBJTD can ameliorate oxidative stress and cell apoptosis levels in D-Gal-induced uterine aging, and its active ingredients can activate the SIRT1/NRF2 pathway to exert its effects. Importantly, our study provides novel insights into the molecular mechanisms by which traditional Chinese medicine influence uterus ageing. By specifically targeting the SIRT1/NRF2 pathway, BJTD presents a unique therapeutic approach that has not been extensively explored in previous studies, marking a significant advancement in the treatment of uterus ageing.

The Impact of Vitamin E Supplementation on Oxidative Stress, Cognitive Functions, and Aging-Related Gene Expression in Aged Mice.

This study investigated the effects of different doses of vitamin E on oxidative stress, cognitive function, and gene expression in aged mice. A total of 32 male mice, aged 12 months, were divided into a control group and three treatment groups. These groups received varying daily doses of vitamin E for a period of 28 days. The results showed significant improvements in cognitive function, specifically in working memory and spatial learning, in the groups that received vitamin E (100, 200, or 400 mg/kg) compared to the control group. The markers of oxidative stress and antioxidant enzyme activities also demonstrated improvements, with higher doses of vitamin E showing greater effects. The analysis of gene expression revealed increased expression of SIRT1, Nrf2, and Calstabin2, particularly at higher doses of vitamin E. These findings suggest that vitamin E supplementation may help counteract age-related cellular changes. The study concludes that vitamin E supplementation can reduce oxidative stress, enhance cognitive function, and affect genetic markers of aging in mice, which may have therapeutic benefits in addressing age-related cognitive decline and oxidative damage. Further research is necessary to investigate the clinical implications of these findings in humans.

Analysis of the evolution of placental oxidative stress research from a bibliometric perspective.

Research on placental oxidative stress is pivotal for comprehending pregnancy-related physiological changes and disease mechanisms. Despite recent advancements, a comprehensive review of current status, hotspots, and trends remains challenging. This bibliometric study systematically analyzes the evolution of placental oxidative stress research, offering a reference for future studies. To conduct a comprehensive bibliometric analysis of the literature on placental oxidative stress to identify research hotspots, trends, and key contributors, thereby providing guidance for future research. Relevant data were retrieved from the Web of Science Core Collection database and analyzed using VOSviewer, CiteSpace, and the bibliometrix package. An in-depth analysis of 4,796 publications was conducted, focusing on publication year, country/region, institution, author, journal, references, and keywords. Data collection concluded on 29 April 2024. A total of 4,796 papers were retrieved from 1,173 journals, authored by 18,835 researchers from 4,257 institutions across 103 countries/regions. From 1991 to 2023, annual publications on placental oxidative stress increased from 7 to 359. The United States (1,222 publications, 64,158 citations), the University of Cambridge (125 publications, 13,562 citations), and Graham J. Burton (73 publications, 11,182 citations) were the most productive country, institution, and author, respectively. The journal Placenta had the highest number of publications (329) and citations (17,152), followed by the International Journal of Molecular Sciences (122 publications). The most frequent keywords were "oxidative stress," "expression," "pregnancy," "preeclampsia," and "lipid peroxidation." Emerging high-frequency keywords included "gestational diabetes mellitus," "health," "autophagy," "pathophysiology," "infection," "preterm birth," "stem cell," and "inflammation." Over the past 3decades, research has concentrated on oxidative stress processes, antioxidant mechanisms, pregnancy-related diseases, and gene expression regulation. Current research frontiers involve exploring pathophysiology and mechanisms, assessing emerging risk factors and environmental impacts, advancing cell biology and stem cell research, and understanding the complex interactions of inflammation and immune regulation. These studies elucidate the mechanisms of placental oxidative stress, offering essential scientific evidence for future intervention strategies, therapeutic approaches, and public health policies.

Physiology, gene expression, and behavior as potential indicators of oxidative stress in piglets

The goal of the current study was to develop a pig model to investigate oxidative stress with a low negative impact on piglet welfare. Four independent trials (A, B, C, and D) were performed using a single intraperitoneal shot of lipopolysaccharide (LPS) as an immune challenge, aiming to assess the minimal LPS dose for piglets of different age to trigger a measurable acute oxidative stress response in healthy animals. In trial A, piglets received an LPS dose of 25 µg/KgBW at 41 days post-weaning (p.w.). In trial B, piglets received 25 µg/KgBW of LPS at 28 days p.w., in trials C And D, piglets were injected with 50 µg/KgBW of LPS at 21 days p.w., respectively. Piglets were randomly allocated either to the T1) Control group with saline solution (Ctrl), or T2) LPS challenge (LPS). The oxidative stress response was measured through the enzymatic activity of glutathione peroxidase (GPx), glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT), in both plasma and intestinal tissues. Intestinal gene expression of oxidative stress and inflammatory markers was assessed. Discomfort behaviors (panting, prostration, trembling, and vomits) were also recorded. Plasmatic and intestinal oxidative stress response was inconsistent across the four trials even when the dose and pig age were similar, possibly due to individual variability. Relative gene expression differences of anti-inflammatory cytokines (IL10), oxidation precursor (iNOS), and antioxidant markers (GPx4, MnSOD, and CAT) were detected between Ctrl and LPS treatment (P < 0.05) when assessed. Behavioral observations were sensitive to the LPS dose relative to Ctrl (P < 0.05) in all four trials. These results suggest that behavioral observations can be used as a non-invasive methodology to detect the presence of oxidative stress in pigs in challenging conditions. Behavioral observations were more sensitive than other indicators (i.e., biomarkers and gene expression) in the current study. However, a sensitivity scale system needs to be developed to qualify and rank the impact of oxidative stress in pigs.

Taurine effects on cell proliferation and gene expression of apoptosis and oxidative stress in broiler satellite cells under heat stress

Taurine effects on cell proliferation and gene expression of apoptosis and oxidative stress in broiler satellite cells under heat stress

13-cis Retinoic Acid-Mediated Modulation of Human Meibomian Gland Epithelial Cells Development: Implications for In Vitro Modeling of Meibomian Gland Dysfunction.

Purpose: This study aimed to investigate the effect of 13-cis retinoic acid (13-cis RA) on human meibomian gland epithelial cells (HMGECs) and explore the potential of using this experimental model as an in vitro approach for studying meibomian gland dysfunction (MGD). Methods: First, HMGECs were cultured with 13-cis RA at different doses and times, and cell viability and proliferation rates were assessed to determine the appropriate stimulation concentration and time. Subsequently, during the proliferation stage, the expression of proliferation, inflammation, and oxidative stress genes and their products were evaluated. The meibum synthesis capacity was determined during the differentiation stage. Additionally, the peroxisome proliferator-activated receptor gamma (PPARγ) antagonist GW9662 was used as a control to assess the impact of 13-cis RA on PPARγ. Results: 13-cis RA significantly inhibited cell viability and proliferation in a time-dose response manner. Under the stimulation of 2 and 5 μM for 48 h during the proliferation stage, a significant decrease was observed in the expression of cell proliferation markers Ki67, antioxidant SOD-2, and Nrf-2. However, the expression of the pro-inflammatory factors IL-1β, IL-8, MMP9, and oxidative stress markers NOX-4 and reactive oxygen species increased. During the differentiation stage, it suppressed meibum synthesis and the expression of meibocyte differentiation-related proteins adipose differentiation-associated protein 4 (ADFP4), elongation of very long chain fatty acid protein 4 (ELOVL4), sterol regulatory element-binding protein 2 (SREBP-2), and PPARγ. Conclusion: 13-cis RA inhibited cell viability, promoted inflammation and oxidative stress, and suppressed meibum synthesis through the PPARγ pathway. Our study shed light on the effect of 13-cis RA on HMGECs and provided a promising direction for studying MGD in vitro.

The effect of rotenone and resveratrol on the expression level of Bcl2 and BAX and the activity of superoxide dismutase enzyme and Malondialdehyde level in the hippocampus of ovariectomized rats.

Background: Exposure to neurotoxins increases the risk of neurodegenerative diseases. Oxidative stress and apoptosis play a central role in the initiation and progression of disorders. Estrogen decrease aggravates oxidative stress and apoptosis caused by neurodegenerative diseases in menopause woman. It is assumed, the use of resveratrol with its antioxidant and protective properties, which has common signaling pathways with estrogen, can be a useful therapeutic approach in preventing the development of oxidative stress and apoptosis. Objective: The present study investigated the protective effect of resveratrol on the change of antioxidant and apoptotic factors caused by rotenone in the hippocampus of ovariectomized rats. Methods: thirty female rats were divided into 5 groups of 6 including rotenone (5m/kg), ovariectomized (bilateral), ovariectomized + rotenone, ovariectomized + resveratrol(40m/kg), and ovariectomized + rotenone + resveratrol. Rotenone was administered intraperitoneally and resveratrol orally for 21 days. At the end, Malondialdehyde, superoxide dismutase (SOD) and expression of BAX and Bcl2 were measured in the hippocampus. Results: Enzyme activity and Bcl2 expression in the rotenone and ovariectomized groups significantly were decreased. BAX expression and Malondialdehyde significantly were increased. Also Resveratrol significantly increased enzyme activity (57.9±1.94 U/mg protein) and Bcl2 expression (0.78±0.05) in ovariectomized + rotenone + resveratrol groups (P≤0.001). Also, resveratrol significantly reduced BAX expression (4.5±0.11) and Malondialdehyde (22.35±1.91 µM/g) in these groups (P≤0.001). Conclusion: Resveratrol improved oxidative stress and apoptosis gene expression changes caused by rotenone and Absence of estrogen in the hippocampus.

Synergistic anticancer effects and reduced genotoxicity of silver nanoparticles and tamoxifen in breast cancer cells

AbstractNanotechnology is emerging as a promising tool to enhance traditional cancer treatments due to rising chemotherapy resistance and the severe side effects of toxic drugs. Silver nanoparticles (AgNPs) are widely acknowledged for their antimicrobial and antiproliferative properties. Given these AgNP characteristics, this research conducts a comprehensive nanotoxicological assessment of strategic combinations involving AgNPs (68 nm) commercial formulation and tamoxifen on MCF‐7 and MDA‐MB‐231 breast tumor cells. Utilizing CompuSyn software, the combination index was determined, revealing a synergistic cytotoxic and antiproliferative effect in AgNPs and tamoxifen combinations (CI &lt; 0.97). Furthermore, this combination impaired cell migration (the scratch zone expanded by over 270%) and significantly increased reactive oxygen species production (up to 96% for MDA‐MB‐231 and 52% for MCF‐7 cells). Surprisingly, the genotoxic effect of these mixtures was minimal (below the allowable genotoxicity index of 1.5). Additionally, both breast tumor cell lines exhibited increased proapoptotic and oxidative stress gene expression following the combined treatment. The internalization of AgNPs into breast cancer cells was observed, enhancing their synergistic antiproliferative effect when combined with tamoxifen. These findings suggest the potential of combining AgNPs with chemotherapeutic agents for innovative studies in oncology therapy.

Therapeutic potential of aquatic Stevia extract in alleviating endoplasmic reticulum stress and liver damage in streptozotocin-induced diabetic rats.

Misfolded proteins accumulate in the liver due to endoplasmic reticulum stress (ERS) caused by high blood glucose levels in diabetes. This triggers the unfolded protein response (UPR), which if persistently activated, results in cellular dysfunction. Chronic ER stress increases inflammation, insulin resistance, and apoptosis. There is growing interest in using native plants and traditional medicine for diabetes treatment. The stevia plant has recently gained attention for its potential therapeutic effects. This study investigates the protective effects of aquatic stevia extract on liver damage, ER stress, and the UPR pathway in streptozotocin (STZ)-induced diabetic rats. Rats were randomly divided into four groups: a control group that received 1ml of water; a diabetic group induced by intraperitoneal injection of STZ (60mg/kg); a diabetic group treated with metformin (500mg/kg); and a diabetic group treated with aquatic extracts of stevia (400mg/kg). After 28 days, various parameters were assessed, including inflammatory markers, oxidative stress indices, antioxidant levels, gene expression, stereology, and liver tissue pathology. Compared to the diabetic control group, treatment with stevia significantly decreased serum glucose, liver enzymes, inflammatory markers, and oxidative stress while increasing body weight and antioxidant levels. Additionally, stevia extract manipulated UPR gene expression and reduced apoptosis pathway activation. Histological examination revealed improved liver tissue morphology in stevia-treated diabetic rats. These findings suggest that aquatic stevia extract mitigates ER stress in diabetic rats by modulating the IRE-1 arm of the UPR and apoptosis pathways, highlighting its potential therapeutic benefits for diabetes-related liver complications.

Potential protective role of chlorogenic acid against cyclophosphamide-induced reproductive damage in male mice.

Cyclophosphamide (CP) is an anticancer drug; however, clinical utilization of CP is limited, resulting from its considerable toxicities. This research was performed to explore the protective effects of Chlorogenic acid (CGA) on reproductive damage induced by CP in mice. Blood samples were collected for analysis of hormone content subsequently; semen samples were evaluated for quality, and testis samples were used for histopathological evaluation and analysis of oxidative stress biomarkers, protein and gene expression levels of steroid regulatory factors, and steroid synthase. The results noted that CGA increased serum testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) activity; increased SOD, GPx, and GSH oxidative stress levels in testis tissue; and decreased MDA content in testis tissue. Testicular cells in the CGA treatment group gradually returned to normal morphology, and CYP11A1 and CYP17A1 levels increased after CGA treatment. The mRNA levels of CYP11A1, CYP17A1, StAR, 3β-HSD, and 17β-HSD were significantly raised in the CGA dose group. In the test dose range, CGA can improve sperm quality, quantitative abnormality, and serum T synthesis disorder caused by CP. This mechanism may be correlated with the inhibition of oxidative stress and antioxidation levels. Therefore, CGA has a protective impact on testicular injuries arising from CP in mice.

"Effect of Sunset Yellow on Testis: Molecular Evaluation, and Protective Role of Coenzyme Q10 in Male Sprague-Dawley Rats".

In recent years, Sunset Yellow (SY) has been widely used as a food additive, sparking debates about its potential toxicity. This research aims to investigate SY's effects at both the molecular and histopathological levels, along with the protective benefits of Coenzyme Q10 (CoQ10) supplementation in male rat testes. Forty-two male Sprague-Dawley rats were randomly divided into six groups (n = 7) and given daily oral gavages for six weeks. The groups included: a low dose of Sunset Yellow (2.5 mg/kg/day), a high dose of Sunset Yellow (70 mg/kg/day), CoQ10 (10 mg/kg/day), CoQ10 with the low dose of Sunset Yellow, CoQ10 with the high dose of Sunset Yellow, and deionized water as a control. After anesthesia, the rats' testes were removed for molecular and histological analysis. The findings showed a dose-dependent rise in the expression of oxidative stress genes (Sod, Gpx, and Cata) and a notable decrease in the expression of the steroidogenic acute regulatory (Star) gene (P value < 0.05) with increasing SY doses. Histological results supported these outcomes. Additionally, there was no significant distinction between rats treated with CoQ10 along with low doses of Sunset Yellow (CoQ10+LD) and control rats given low doses of Sunset Yellow (SY-LD). Conclusions: This study illustrates that SY, as an artificial food dye, has harmful effects on the male reproductive system, while the utilization of CoQ10 can alleviate the negative impacts of SY exposure.

Biochemical and transcriptomic analyses reveal the toxicological response and potential mechanism of butyl benzyl phthalate in zebrafish gills

Butyl benzyl phthalate (BBP), a common phthalate plasticizer, is frequently detected in aquatic environments. However, there has been relatively little research on its effects on gill-related responses. This study exposed adult zebrafish to BBP concentrations ranging from 5 to 500 μg/L for 28 days, specifically investigating its toxicity in the gills. Assessment of oxidative stress biomarkers and gene expression related to apoptosis and mitochondria was conducted. Results demonstrated that exposure to 500 μg/L of BBP disrupted the antioxidant defense system, leading to lipid peroxidation and DNA damage. Moreover, the expression level of the caspase-3 gene exhibited an approximate two-fold increase, whereas the expression of 18rs-rrn decreased by 50 % on day 28. Gene Ontology enrichment analysis indicated suppressed expression of antioxidant and metabolic process terms, alongside inhibition of metabolism, immune, and signal transduction-related pathways. This study offers novel insights into the toxic effects and mechanisms of BBP on fish, providing valuable data for assessing environmental risks linked to BBP contamination and advocating for its management in aquatic ecosystems.

Monocarbonyl analogs of curcumin C66 and B2BrBC modulate oxidative stress, JNK activity, and pancreatic gene expression in rats with streptozotocin-induced diabetes

The pathogenesis of type 1 diabetes mellitus (T1DM) involves oxidative stress and inflammation. Curcumin, a natural polyphenolic compound found in turmeric, known to exhibit antioxidative and anti-inflammatory properties, is characterized by poor chemical stability, low bioavailability, and rapid metabolism. Monocarbonyl analogs of curcumin (MACs) with a structural absence of β-diketone and enhanced stability and bioavailability present a potential solution to the challenges associated with the use of curcumin. This study aimed to evaluate the effect of two MACs, C66 and B2BrBC, on oxidative stress markers, antioxidant enzyme activity, expression of diabetes-associated genes, and signaling pathway proteins in the context of T1DM. Streptozotocin (STZ)-induced male Wistar rats or rat pancreatic RIN-m cells were used for in vivo and in vitro experiments, respectively. C66 or B2BrBC were given either before or after STZ treatment. Oxidative stress markers and antioxidant enzyme activities were determined in various tissues. Expression of diabetes-associated genes was assessed using RT-qPCR, and the activity of signaling pathway proteins in the pancreas was determined through Western blot analysis. Treatment with C66 and B2BrBC significantly reduced oxidative stress markers and positively influenced antioxidant enzyme activities. Moreover, both compounds inhibited JNK activity in the pancreas while enhancing the expression of genes crucial for β-cell survival and glucose and redox homeostasis. The findings highlight the multifaceted potential of C66 and B2BrBC in ameliorating oxidative stress, influencing gene expression patterns linked to diabetes, and modulating key signaling pathways in the pancreas. The findings suggest that these compounds can potentially address diabetes-related pathological processes.

Oxidative Stress, Oxidative Damage, and Cell Apoptosis: Toxicity Induced by Arecoline in Caenorhabditis elegans and Screening of Mitigating Agents.

As the areca nut market is expanding, there is a growing concern regarding areca nut toxicity. Areca nut alkaloids are the major risky components in betel nuts, and their toxic effects are not fully understood. Here, we investigated the parental and transgenerational toxicity of varied doses of areca nut alkaloids in Caenorhabditis elegans. The results showed that the minimal effective concentration of arecoline is 0.2-0.4 mM. First, arecoline exhibited transgenerational toxicity on the worms' longevity, oviposition, and reproduction. Second, the redox homeostasis of C. elegans was markedly altered under exposure to 0.2-0.4 mM arecoline. The mitochondrial membrane potential was thereafter impaired, which was also associated with the induction of apoptosis. Moreover, antioxidant treatments such as lycopene could significantly ameliorate the toxic effects caused by arecoline. In conclusion, arecoline enhances the ROS levels, inducing neurotoxicity, developmental toxicity, and reproductive toxicity in C. elegans through dysregulated oxidative stress, cell apoptosis, and DNA damage-related gene expression. Therefore, the drug-induced production of reactive oxygen species (ROS) may be crucial for its toxic effects, which could be mitigated by antioxidants.

Mechanistic insights into acetamiprid-induced genotoxicity on the myocardium and potential ameliorative role of resveratrol

The current study aimed to explore the genotoxic impacts of the insecticide acetamiprid (ACP) on the myocardium and assess the ameliorative role of resveratrol (RSV). Male rats (10/group) were treated via oral route for 90 days: control; ACP (25 mg/kg); RSV (20 mg/kg); ACP+RSV. Peripheral blood micronucleus test, oxidative stress analysis, comet assay, 8-hydroxydeoxyguanosine and gene expression assessment were performed. The findings revealed that ACP has myocardial genotoxic effects, as demonstrated by increased micronucleus and 8-hydroxydeoxyguanosine formation and increased all comet parameters. Oxidative stress analysis demonstrated that ACP elevated H2O2 and NO levels while decreasing catalase and GST activities. Acetamiprid dysregulated the expression of genes related to oxidative stress and DNA damage response. However, RSV co-treatment resulted in significant protection against these genotoxic impacts. Resveratrol reduced DNA damage and restored the oxidative balance in the myocardium. Moreover, RSV modulated the Nrf2/HO-1 and Atm/P53 pathways, potentiating antioxidant defense and DNA repair.

Comparative role of calcium oxide nanoparticles and calcium bulk fertilizer to alleviate cadmium toxicity by modulating oxidative stress, photosynthetic performance and antioxidant-defense genes expression in alfalfa

Cadmium (Cd) toxicity poses a significant threat to soil health and sustainable food production. Its bioaccumulation in plant tissues induces phytotoxicity by affecting physiological and biochemical attributes, leading to a reduction in plant biomass and production. Recently, nanotechnology has emerged as a promising approach for addressing heavy metal toxicity in an eco-friendly manner to enhance crop production. However, the comparative role of foliar applied calcium oxide nanoparticles (CaO-NPs) and bulk calcium fertilizer under Cd stress in alfalfa remains unexplored. Herein, we studied the ameliorative role of CaO-NPs and bulk calcium (50 and 100 mg L−1) to alleviate Cd stress (30 mg kg−1) in alfalfa seedlings. Plants exposed to Cd exhibited significant decreases in morpho-physiological traits, gas exchange attributes, and pigment contents as well as increase in Cd bioaccumulation in plant tissues. Notably, exogenous application of CaO-NPs ameliorates the toxic impact of Cd by enhancing plant biomass (45%), fluorescence efficiency and gaseous exchange attributes. The maximum dose of CaO-NPs induced Cd-tolerance response accompanied by a significant increase in antioxidative enzyme activities, such as superoxide dismutase (SOD; 29%), peroxidase (POD; 41%), catalase (CAT; 36%) and ascorbate peroxidase (APX; 49%), which play positive roles in ROS scavenging. TEM examination further revealed the protective role of these NPs in averting Cd-induced damage to leaf ultrastructure and mesophyll cells. Furthermore, CaO-NPs had a substantial influence on both Cd and Ca2+ accumulation in plant tissues, while qRT‒PCR analysis demonstrated higher expression of antioxidant defense genes viz. Cu/ZnSOD (0.38 fold change (FC)), MtPOD (0.51 FC), MtCAT (0.61 FC) and MtAPX (0.79 FC) under CaO-NPs application, over Cd control. Overall, our findings suggested that exogenous CaO-NPs could be effective in alleviating the adverse effects of Cd on alfalfa seedlings to ensure food safety and support sustainable agriculture.