The contamination of edible agricultural goods with pesticides, including dichlorvos (DVDP), poses a substantial public health risk, promoting severe morbidity and mortality, especially in developing countries. It has been shown that hesperidin (hesperetin-7-O-rhamnoglucoside or Hes-7-RGlc) preserves cytomembrane, redox, and lipid homeostasis; unfortunately, its function on dichlorvos-incited heart damage has not been investigated. This work explored the ameliorative influence of Hes-7-RGlc on DVDP-activated cardiotoxicity. For this end, forty-two rats were randomly appropriated into seven groups (6 rats/group): Control, DVDP alone (8 mg.kg⁻¹day⁻¹), DVDP supplied with either Hes-7-RGlc (50 and 100 mg.kg⁻¹day⁻¹) or the reference medication atropine (0.2 mg.kg⁻¹day⁻¹), and Hes-7-RGlc alone (50 and 10 mg.kg⁻¹day⁻¹) were the seven groups investigated. DVDP was administered orally for seven days, followed by fourteen days of Hes-7-RGlc therapy. Then the rats were euthanized, and their blood and hearts were removed. Hes-7-RGlc chemotherapy substantially (p<0.05) restored DVDP-elicited dynamics in plasma and cardiac/myocardium creatine kinase isoenzyme (CK-MB), major lipids (cholesterol, triacylglycerol, and phospholipids), electrolytes (Na⁺, K⁺, Ca²⁺, Mg²⁺, Cl⁻), and total protein. Hes-7-RGlc remedy decidedly (p<0.05) abolished DDVP-stimulated amplification in the cardiac concentration of H₂O₂, NO and malondialdehyde; annulled DVDP-educed decreases in heart GSH levels, activities of GST, SOD, catalase, and glutathione peroxidase, ion transporters (Na⁺/K⁺-ATPase and Ca²⁺/Mg²⁺-ATPase), ALT, AST, ALP, and LDH-1. Collectively, Hes-7-RGlc can be advocated as a natural supplementary candidate and blocker of DVDP-provoked heart deficits via its capacity to reverse disruptions of electrolytes, ion pumps, redox status, and lipid homeostasis.

BACKGROUND: Selective deprivation of glutamine has been shown to accelerate the generation of reactive oxygen species (ROS) and to impair the activity of a specific pentose phosphate pathway (PPP) located within the endoplasmic reticulum (ER). The consequent oxidative damage suggests that glucose flux through this reticular pathway might contribute to the redox stress of breast cancer cells. We thus evaluated whether this response is reproduced when the glutamine shortage is coupled with the glucose deprivation.
METHODS: Cancer growth, metabolic plasticity and redox status were evaluated under saturating conditions and after 48 h starvation (glucose 2.5 mM, glutamine 0.5 mM). The Seahorse technology was used to estimate adenosine triphosphate (ATP)-linked and ATP-independent oxygen consumption rate (OCR) as well as proton efflux rate (PER). 18F-fluoro-deoxy-glucose (FDG) uptake was evaluated through the LigandTracer device. Proliferation rate was estimated by the carboxyfluorescein-diacetate-succinimidyl ester (CFSE) staining, while cell viability by the propidium iodide exclusion assay.
RESULTS: Starvation reduced the proliferation rate of MCF-7 cells without affecting their viability. It also decreased lactate release and PER. Overall OCR was left unchanged although ATP-synthase dependent fraction was increased under nutrient shortage. Glutaminolysis inhibition selectively impaired the ATP-independent and the oligomycin-sensitive OCR in control and starved cultures, respectively. The combined nutrient shortage decreased the cytosolic and mitochondrial markers of redox stress. It also left unchanged the expression of the reticular unfolded protein marker GRP78. By contrast, starvation decreased the expression of hexose-6P-dehydrogenase (H6PD) thus decreasing the glucose flux through the ER-PPP as documented by the profound impairment in the uptake rate of FDG.
CONCLUSIONS: When combined with glucose deprivation, glutamine shortage does not elicit the expected enhancement of ROS generation in the studied breast cancer cell line. Combined with the decreased activity of ER-PPP, this observation suggests that glutamine interferes with the reticular glucose metabolism to regulate the cell redox balance.

Glutathione (GSH) is a non-protein tripeptide thiol that plays a prominent role in oxidative stress defense. GSH concentration is particularly critical in the neonatal period, especially for premature newborns that face increased susceptibility to oxidative stress. Monitoring GSH levels provides valuable insights into newborn health, helping to tailor care to their specific needs. The aim of this study was the development of a sensor specifically targeted for its use in neonatology, enabling GSH determination in only 2 μL of whole blood. The newly developed sensing system simplifies sample processing, addressing a critical need in clinical applications. Unlike current methods that demand fast pre-processing of relatively large sample volumes, expensive equipment, and skilled personnel, the developed approach streamlines the analytical process. By using 2 μL of whole blood, a single syringe filter for sample treatment, a deuterated internal standard (IS) for signal normalization, and Surface Enhanced Raman Scattering (SERS) spectroscopy with a silver colloid substrate for GSH detection, the set-up\'s characteristics are compatible with point-of-care applications. The analytical procedure was validated and applied to diverse populations including healthy adults (N = 63) and newborns (N = 35), yielding GSH concentration values ranging from 0.6 to 1.8 and 0.8-2.1 mM, respectively. This new optical sensor offers a quick and cost-effective solution to support the assessment of GSH levels in newborns that can greatly benefit not only neonatal care, but also the study of adult populations for health monitoring.

Glutathione (GSH) is indispensable for maintaining redox homeostasis in biological fluids and serves as a key component in cellular defense mechanisms. Accurate assessment of GSH relative to its oxidized counterpart, glutathione disulfide (GSSG), is critical for the early diagnosis and understanding of conditions related to oxidative stress. Despite existing methods for their quantification, the label-free and simultaneous measurement of GSH and GSSG in biological fluid presents significant challenges. Herein, we report the use of an alpha-hederin (Ah) nanopore for the direct measurement of the GSH:GSSG ratio in simulated biological fluid, containing fetal bovine serum (FBS). This system hinges on detecting characteristic relative ion blockades (ΔI/Io) as GSH and GSSG molecules pass through the Ah nanopore under an applied electric field. The distinct current blockage signals derived from the translocation of GSH and GSSG enabled us to determine the molar ratio of GSH and its oxidized form. Notably, the interactions between the hydroxyl groups of the sugar moiety lining the nanopore\'s inner surface and the sulfhydryl group of GSH significantly influence the translocation dynamics, resulting in a longer translocation time for GSH compared to GSSG. The Ah nanopore technology proposed in this study offers a promising approach for real-time, single molecule-level monitoring of glutathione redox status in biological fluids, eliminating the need for labeling or extensive sample preparation.

Anxiety disorders are the most prevalent psychiatric disorders, exhibiting strong female bias. Clinical studies implicate declining estradiol levels in the exacerbation of anxiety symptoms in the premenstrual phase of the menstrual cycle. This study aimed to simulate estradiol fluctuation-linked anxiety behavior in larval zebrafish, using an estradiol treatment withdrawal model. Contrary to model aims, estradiol treatment withdrawal decreased both basal activity and anxiety-like hyperlocomotion (ANOVA main effect of dose, P < 0.0001 and P < 0.01, respectively) in the light/dark transition test. The accuracy of the estradiol washout model was not improved by longer durations of treatment or withdrawal. Basal activity was slightly altered by supraphysiological concentrations of WAY-200070 in the absence of added estradiol. Estrogen receptor (ER) β expression was not upregulated in larvae exposed to physiologically relevant, low concentrations of estradiol. Longer exposure to low concentrations of estradiol increased antioxidant capacity (P < 0.01). In addition, acute exposure to low concentrations of estradiol increased basal activity. Data suggest that in the current models, estradiol-associated altered activity levels were linked to more favorable redox status, rather than reflecting altered anxiety levels. As such, it is recommended that zebrafish larval behavioral analysis be conducted in parallel with mechanistic studies such as redox indicators, for investigations focused on ER signaling.

This experiment was performed to identify the influence of dietary Saussurea lappa root (SLR) on the performance and general health status of Nile Tilapia fingerlings (O. niloticus). Four formulated diets with different SLR levels of 0.0, 2.5, 5 and 10 g/kg, respectively, were afforded to fingerling fish (15.42 ± 0.05 g) for 8 weeks. The feed efficiency ratio (FER), feed intake (FI) and feed conversion ratio varied with dietary SLR level in a linear model and a high feed efficiency rate was recorded at the 10 g/kg group, while FI and FCR exhibited an opposite trend (P < 0.001). Dietary SLR level influenced serum protein constituents, liver and renal function enzymes, triglycerides, cholesterol and glucose (P < 0.001). Serum Catalase (CAT), total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) remarkedly increased with dietary SLR level and attained a level at 10 g/kg. Furthermore, serum lysozyme, complement C3 (C3), IgA and IgD were stimulated by 10 g/kg SLR. Intestinal digestive enzymes (lipase and amylase) increased with SLR level up to 10 g/kg. As the dietary SLR level raised, the cumulative survival percentage aginst A. hydrophila challenge increased and then reached a maximum at 10 g/kg SLR group. Moreover, gene expression of pro-inflammation cytokines (TNF-2a, IL-1β, and IL-10) in liver and kidney transcriptomes demonstrated effective immunostimulant capabilities of greater SLR inclusion levels in fish diet. Meanwhile, intestinal microbial investigation, revealed that high levels of SLR in tilapia fish feed significantly suppressed total bacterial count, and pathogenic bacterial count (such as, E. coli, Coliform, Aeromonas spp, Pseudomonas spp.), and stimulated lactic acid bacteria development. Finally, it is recommended to include a high level of SLR (5 or 10 g/kg) in the diet of O. niloticus fingerlings to enhance feed efficiency, antioxidant characteristics, and immunological response against bacterial infections.

Background Drug and substance abuse remains a major medical problem worldwide. Amphetamines are potent stimulants of the central nervous system. Amphetamine abuse is highly prevalent among drug-dependents. This study was conducted in Qassim, Saudi Arabia, to evaluate amphetamine\'s toxic effects on major and trace elements and their correlation with redox status. Methods The study involved amphetamine-only patients admitted to the Erada Rehabilitation Centre from March to October 2023. Urine samples were analysed from both normal subjects and amphetamine-dependent groups. Results Urinary sodium and chloride levels were significantly higher in the amphetamine-dependent group than in the control group, while their calcium levels decreased. Lipid peroxidase levels significantly increased in people with a substance use disorder (SUD), indicating oxidative stress. Together, their total antioxidant capacity decreased. Zinc (Zn), copper (Cu), lead (Pb), cadmium (Cd), sodium (Na), and total antioxidant capacity levels were positively correlated with lipid peroxidase. Conclusions Amphetamine-dependent people are more likely to experience a variety of health problems. This study found a direct correlation between an imbalance in major and trace elements and the redox status.

Heat stress is one of the stressors that negatively affect broiler chickens, leading to a reduction in production efficiency and profitability. This reduction affects the economy in general, especially in hot and semi-hot countries. Therefore, improving heat tolerance of broiler chicks is a key to sustained peak performance, especially under adverse environmental heat stress conditions. The present study investigated three early feed withdrawal regimes (FWD) as a potential mitigation for thermal stress exposure. A total of 240 unsexed one-day-old Cobb-500 chicks were randomly recruited to one of four experimental groups using a completely randomized design (10 birds × 6 replicates). The experimental groups included the control group with no feed withdrawal (control), while the other three groups were subjected to early feed withdrawal for either 24 h on the 5th day of age (FWD-24), 12 h on the 3rd and 5th day of age (FWD-12), or 8 h on the 3rd, 4th, and 5th day of age (FWD-8), respectively. Production performance was monitored throughout the experiment. Meanwhile, blood and liver samples were taken at the end of the experimental period to evaluate major physiological dynamic changes. Our findings demonstrated that under chronic heat stress conditions, FWD treatments significantly improved broilers\' production performance and enhanced several physiological parameters compared with the control. Serum levels of thyroid hormones were elevated, whereas leptin hormone was decreased in FWD groups compared with the control. Moreover, serum total protein, globulin, and hemoglobin levels were higher, while total cholesterol and uric acid were lower in the FWD groups. Furthermore, FWD groups showed significantly higher antioxidant marker activity with a significantly lower lipid peroxidation level. Immunoglobulin levels, lysozyme, complement factor C3, and liver heat shock protein 70 (HSP70) concentration were also elevated in FWD compared with the control. Also, serum interleukin-1β (IL-1β) and interferon-gamma (IFN-γ) significantly increased with FWD. Based on our findings, early feed withdrawal can be applied as a promising non-invasive nutritional strategy for broilers reared under chronic heat stress conditions. Such a strategy promotes the alleviation of the deleterious effects of heat stress on broiler performance, immunity, and redox status, owing to the onset of physiological adaptation and the development of thermotolerance ability.

Glutamine, one of the most abundant amino acids in the body, has been shown to exert various beneficial effects in pigs. However, knowledge regarding the role of dietary glutamine in low-protein diet-fed piglets remains scarce. The present study aimed to investigate the effects of different levels of L-glutamine on growth performance, serum biochemistry parameters, redox status, amino acids, and fecal microbiota in low-protein diet-fed piglets. A total of 128 healthy crossbred piglets (Landrace × Yorkshire) were randomly allocated into 4 groups of 4 replicate pens, with 8 piglets per pen. Piglets in the 4 groups were fed with corn and soybean meal-based low-protein diets (crude protein level, 17%) that contained 0%, 1%, 2%, and 3% L-glutamine, respectively, for 28 d. Pigs administered 1% L-glutamine had greater body weight on d 28 and average daily gain (ADG, P < 0.01), whereas a lower feed to gain ratio (F:G) from d 1 to 28 (P < 0.01), compared to the other three groups. Besides, lower body weight on d 14 and 28, ADG, average daily feed intake, and higher F:G from d 15 to 28 and d 1 to 28 were observed in response to 2% and 3% L-glutamine treatments than 0% and 1% L-glutamine treatments (P < 0.01). Moreover, 1% L-glutamine reduced serum glucose, malondialdehyde, hydrogen peroxide concentrations and inhibited aspartate aminotransferase, alanine aminotransferase, myeloperoxidase activities in low-protein diet-fed piglets on d 14, with concomitantly upregulated catalase, total superoxide dismutase activities and glutathione level (P < 0.05). However, dietary 3% L-glutamine enhanced blood urea nitrogen content in pigs on d 14 (P < 0.05). Further investigation revealed that 1% L-glutamine upregulated the serum glutamine, lysine, methionine, tyrosine, and reduced plasma valine content (P < 0.05). Additionally, 1% L-glutamine upregulated the abundance of p_75_a5, Clostridium, Lactobacillus, Prevotellaceae_Prevotella, and Gemmiger in the stool of piglets on d 14, with the Streptococcus level being concomitantly reduced (P < 0.05). Collectively, dietary 1% L-glutamine enhances the growth performance and improves serum physiochemical parameters and antioxidative capacity in low-protein diet-fed piglets at an early age, which are associated with an increased synthesis of glutathione by modulating amino acid levels, and the optimization of gut microbiota.

Factors that reduce the risk of developing colorectal cancer include biologically active substances. In our previous research, we demonstrated the anti-inflammatory, immunomodulatory, and antioxidant effects of oat beta-glucans in gastrointestinal disease models. The aim of this study was to investigate the effect of an 8-week consumption of a diet supplemented with low-molar-mass oat beta-glucan in two doses on the antioxidant potential, inflammatory parameters, and colonic metabolomic profile in azoxymethane(AOM)-induced early-stage colorectal cancer in the large intestine wall of rats. The results showed a statistically significant effect of AOM leading to the development of neoplastic changes in the colon. Consumption of beta-glucans induced changes in colonic antioxidant potential parameters, including an increase in total antioxidant status, a decrease in the superoxide dismutase (SOD) activity, and a reduction in thiobarbituric acid reactive substance (TBARS) concentration. In addition, beta-glucans decreased the levels of pro-inflammatory interleukins (IL-1α, IL-1β, IL-12) and C-reactive protein (CRP) while increasing the concentration of IL-10. Metabolomic studies confirmed the efficacy of oat beta-glucans in the AOM-induced early-stage colon cancer model by increasing the levels of metabolites involved in metabolic pathways, such as amino acids, purine, biotin, and folate. In conclusion, these results suggest a wide range of mechanisms involved in altering colonic metabolism during the early stage of carcinogenesis and a strong influence of low-molar-mass oat beta-glucan, administered as dietary supplement, in modulating these mechanisms.