Oxidative Markers Research Articles

Effects of different doses of computed tomography radiation on the oxidation markers, antioxidant enzymes, and lipid profiles of male albino rats

Effects of different doses of computed tomography radiation on the oxidation markers, antioxidant enzymes, and lipid profiles of male albino rats

The Role of Intra-Articular Delivery of BM-MSCs-Derived Exosomes in Improving Osteoarthritis: Implication of circYAP1/miRNA-21/TLR7 Axis.

Bone marrow-derived mesenchymal stem cells (BM-MSCs) have recently attracted great attention due to their crucial anti-inflammatory and regenerative properties. This work aims to examine the curative impact of intra-articular injection of BM-MSCs-derived exosomes in ameliorating osteoarthritis (OA) progression in rats and to explore the interaction between circular RNA of Yes-associated protein 1 (circYAP1) and microRNA-21 (miRNA-21) in the rat knee joints. Gene expression circYAP1, miRNA-21, toll-like receptor-7 (TLR7), aggrecan, and collagen type II were evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in the rat articular tissues. In addition, the Enzyme-linked immunosorbent assay (ELISA) technique was used to estimate the level of the inflammatory markers interleukin 4 (IL-4), interleukin 10 (IL-10), interleukin 1β (IL-1β), and tumor necrosis factor-alpha (TNF-α); and the oxidative markers glutathione (GSH), malondialdehyde (MDA) and total reactive oxygen species (ROS). Histopathological examination using Hematoxylin and Eosin (H&E) staining of the rat articular tissue was also performed along with an estimation of the articular cartilage thickness. Our results showed that BM-MSCs-derived exosomes significantly elevated circYAP1 gene expression level (p < 0.05) along with subsequent downregulation of miRNA-21 and TLR7 (p < 0.05). These effects impacted the inflammatory milieu of rat articular surfaces, where there was a significant reduction (p < 0.05) of the pro-inflammatory and oxidative markers with significantly increased production of the anti-inflammatory and antioxidative markers (p < 0.05). Marked elevation in aggrecan and collagen type II gene expression was also found in the treated groups (p < 0.05). Those data suggest that BM-MSCs-derived exosomes have a crucial role in mitigating OA symptoms and pathology progression and might be regarded as an effective as well as acceptable treatment option for OA.

Pterostilbene Effect on Inflammatory and Oxidation Markers in Benign Prostatic Hyperplasia Rats Model

Pterostilbene is a potent anti-inflammatory and antioxidant used to treat benign prostatic hyperplasia, which is brought on by the induction of testosterone propionate. The objective of the current experiment was to assess the efficacy of pterostilbene treatment in comparison to finasteride and resveratrol by tracking various inflammatory and oxidative markers in a male rat with lower urinary tract symptoms consistent with benign prostatic hyperplasia. The forty-eight male rats were divided into sex groups: the control group, which included eight rats given oil vehicle subcutaneously for 42 days; the induction group, which included eight rats given testosterone propionate(4mg/kg/day) subcutaneously daily dose for fourteen days; and the finasteride group, which included eight rats given finasteride 0.44 mg/kg orally for twenty-eight days after induction Benign prostatic hyperplasia , and the Pterostilbene group, which consisted of 8 rats, got Pterostilbene 200 mg/kg administered orally for 28 days after 14 day Benign prostatic hyperplasia induction, and the other group, which consisted of 8 rats, received Pterostilbene at a dose of 100 mg/kg Use oral gavage to provide 100 mg/kg for the same time period. While the Resveratrol group, which received 100 mg/kg of resveratrol orally. During the identical time frame after Benign prostatic hyperplasia Induction. There were significant differences in the tissue levels of inflammatory markers and oxidative markers Tumor necrosis factor alpha and Glutathione-peroxidase &amp; Malondialdehyde when comparing the pterostilbene 200 group to the induction group (P ≤0.05). Pterostilbene has potent antioxidant and anti-inflammatory properties that help to lessen the growth of the benign prostatic hyperplasia that testosterone propionate causes.

Analysis of quality-related proteins in golden pompano (Trachinotus ovatus) fillets with modified atmosphere packaging under superchilling storage

Here, we aimed to study the changes in proteome of golden pompano fillets during post-mortem storage. Tandem mass tags (TMT)-labeled quantitative proteomic strategy was applied to investigate the relationships between protein changes and quality characteristics of modified atmosphere packaging (MAP) fillets during superchilling (-3 ℃) storage. Scanning electron microscopy was used to show that the muscle histology microstructure of fillets was damaged to varying degrees, and low-field nuclear magnetic resonance was used to find that the immobile water and free water in the muscle of fillets changed significantly. Total sulfhydryl content, TCA-soluble peptides and Ca2+-ATPase activity also showed that the fillet protein had a deterioration by oxidation and denaturation. The Fresh (FS), MAP, and air packaging (AP) groups were set. Total of 150 proteins were identified as differential abundant proteins (DAPs) in MAP/FS, while 209 DAPs were in AP/FS group. The KEGG pathway analysis indicated that most DAPs were involved in binding proteins and protein turnover. Correlation analysis found that 52 DAPs were correlated with quality traits. Among them, 8 highly correlated DAPs are expected to be used as potential quality markers for protein oxidation and water-holding capacity. These results provide a further understanding of the muscle deterioration mechanism of packaging golden pompano fillets during superchilling.

Notoginsenoside Fc alleviates oxidized low-density lipoprotein-induced endothelial cell dysfunction and upregulates PPAR-γ in vitro.

Deep venous thrombosis (DVT) is a prevalent vascular disease and a major cause of morbidity and mortality worldwide. Notoginsenoside Fc (NFc) is a protopanaxadiol-type saponin that has been shown to have beneficial effects on several disorders. However, its function in DVT is unclear. Human umbilical vein endothelial cells (HUVECs) were treated with oxidized low-density lipoprotein (ox-LDL) to mimic DVT in vitro and treated with NFc to investigate its functions. CCK-8 assay was utilized for measuring cell viability. Western blotting was used for detecting protein levels of proinflammatory cytokines, apoptosis-related markers, and peroxisome proliferator-activated receptor-γ (PPAR-γ). Flow cytometry was performed for cell apoptosis detection. Levels of oxidative stress-related markers were examined by the DCFH-DA method and ELISA. RT-qPCR was utilized for the measurement of PPAR-γ mRNA level. NFc increased the viability and suppressed inflammation, apoptosis, and oxidative stress in ox-LDL-treated HUVECs. NFc treatment induced upregulation of PPAR-γ in HUVECs. NFc mitigates ox-LDL-induced dysfunction of HUVECs.

Chronic exposure to TiO2 micro- and nano particles: A biochemical and histopathological experimental study.

The aim of this work was to analyze the effects of long-term exposure to titanium dioxide (TiO2) micro- (MPs) and nanoparticles (NPs) (six and 12 months) on the biochemical and histopathological response of target organs using a murine model. Male Wistar rats were intraperitoneally injected with a suspension of TiO2 NPs (5 nm; TiO2-NP5 group) or MPs (45 μm; TiO2-NP5 group); the control group was injected with saline solution. Six and 12 months post-injection, titanium (Ti) concentration in plasma and target organs was determined spectrometrically (ICP-MS). Blood smears and organ tissue samples were evaluated by light microscopy. Liver and kidney function was evaluated using serum biochemical parameters. Oxidative metabolism was assessed 6 months post-injection (determination of superoxide anion by nitroblue tetrazolium (NBT) test, superoxide dismutase (SOD) and catalase (CAT), lipid peroxidation, and paraoxonase 1). Titanium (Ti) concentration in target organs and plasma was significantly higher in the TiO2-exposed groups than in the control group. Histological evaluation showed the presence of titanium-based particles in the target organs, which displayed no structural alterations, and in blood monocytes. Oxidative metabolism analysis showed that TiO2 NPs were more reactive over time than MPs (p < .05) and mobilization of antioxidant enzymes and membrane damage varied among the studied organs. Clearance of TiO2 micro and nanoparticles differed among the target organs, and lung clearance was more rapid than clearance from the lungs and kidneys (p < .05). Conversely, Ti concentration in plasma increased with time (p < .05). In conclusion, neither serum biochemical parameters nor oxidative metabolism markers appear to be useful as biomarkers of tissue damage in response to TiO2 micro- and nanoparticle deposits at chronic time points.

Pregnancy-induced oxidative stress and inflammation are not associated with impaired maternal neuronal activity or memory function.

Pregnancy is associated with neural and behavioral plasticity, systemic inflammation, and oxidative stress, yet the impact of inflammation and oxidative stress on maternal neural and behavioral plasticity during pregnancy is unclear. We hypothesized that healthy pregnancy transiently reduces learning and memory and these deficits are associated with pregnancy-induced elevations in inflammation and oxidative stress. Cognitive performance was tested with novel object recognition (recollective memory), Morris water maze (spatial memory), and open field (anxiety-like) behavior tasks in female Sprague-Dawley rats of varying reproductive states [nonpregnant (nulliparous), pregnant (near term), and 1-2 mo after pregnancy (primiparous); n = 7 or 8/group]. Plasma and CA1 proinflammatory cytokines were measured with a MILLIPLEX magnetic bead assay. Plasma oxidative stress was measured via advanced oxidation protein products (AOPP) assay. CA1 markers of oxidative stress, neuronal activity, and apoptosis were quantified via Western blot analysis. Our results demonstrate that CA1 oxidative stress-associated markers were elevated in pregnant compared with nulliparous rats (P ≤ 0.017) but there were equivalent levels in pregnant and primiparous rats. In contrast, reproductive state did not impact CA1 inflammatory cytokines, neuronal activity, or apoptosis. Likewise, there was no effect of reproductive state on recollective or spatial memory. Even so, spatial learning was impaired (P ≤ 0.007) whereas anxiety-like behavior (P ≤ 0.034) was reduced in primiparous rats. Overall, our data suggest that maternal hippocampal CA1 is protected from systemic inflammation but vulnerable to peripartum oxidative stress. Peripartum oxidative stress elevations, such as in pregnancy complications, may contribute to peripartum neural and behavioral plasticity.NEW & NOTEWORTHY Healthy pregnancy is associated with elevated maternal systemic and brain oxidative stress. During postpregnancy, brain oxidative stress remains elevated whereas systemic oxidative stress is resolved. This sustained maternal brain oxidative stress is associated with learning impairments and decreased anxiety-like behavior during the postpregnancy period.

Rancidity development in oat during industrial processing

To improve the shelf-life of food products rich in lipids, it is important to minimize the lipid oxidation that occurs during processing, since this oxidation not only decreases shelf-life but also induces off-flavors. To evaluate the oxidation of lipids in the production of one β-glucan-rich and one protein-rich food supplement made from oats (Avena sativa), the neutral and polar lipid profile, hexanal content, peroxide value, avenanthramides and lipase activity were measured at all production steps. The concentration of antioxidants in the form of avenanthramides was also investigated. This study shows that oat lipases were fully inactivated in the wet processing part of the processing line, and the total lipid content per dry weight increased with the progression of steps toward the oat protein product. Processing had no apparent effect on avenanthramide levels. Lipid oxidation markers increased in certain processing steps. The most significant increase in hexanal and peroxide values could be seen in the spray-drying step of the process, while a much smaller increase was seen for the drum-drying. The main conclusion is that the most important factor to prolong the shelf-life of the product is to minimize the oxidation in the drying step.

Unveiling of the anti-tumor activity of green synthesized zinc nanoparticles against Ehrlich solid tumors in mice

Cancer as a threat to human life disease is considered by the disturbance of the normal cell cycle, which results in the spontaneous growth of cell growth, the lack of differentiation, and consequently malignant growths. Nowadays, various synthetic agents are applied for cancer therapy; nevertheless, the reports confirmed that these chemical agents are related to various adverse complications. This experimental study was designed to assess the anti-tumor activities of zinc nanoparticles (ZnNP) green synthesized by the Astragalus maximus against the Ehrlich solid tumors (EST) in mice. To induce the EST model, 0.2 ml of cell suspension was intramuscularly injected into the right thigh of the mice. Five-day post-injection, the mice were allocated into five groups (containing 8 mice/each group) including EST mice treated with normal saline, EST mice orally treated ZnNP 10 mg/kg/day, EST mice orally treated ZnNP 25 mg/kg/day, and EST mice orally treated ZnNP 50 mg/kg/day for 14 days. Then, the volume of the tumor, tumor growth inhibition, body weight, the tumor markers, oxidant/antioxidant markers, and tumor necrosis factor-alpha level (TNF-α), were assessed in tested mice. Our results showed that after the treatment of EST mice with CYC and ZnNPs at 10, 25, and 50 mg/kg, the volume of tumor and serum amount of tumor markers of AFP and CEA were significantly reduced (p&lt;0.001). We found that ZnNPs at 10, 25, and 50 mg/kg markedly declined the oxidative markers and increased the level of antioxidant enzyme of SOD and GPx in comparison with the control group received normal saline (p&lt;0.001). To conclude, we reported the unveiling of the anti-tumor activity of ZnNPs green synthesized by A. maximus extract mainly at the doses 50 mg/kg against Ehrlich solid tumors (EST) in mice; however, further supplementary studies are required to clear all anti-tumor aspects of these nanoparticles.

Life-history stage influences immune investment and oxidative stress in response to environmental heterogeneity in Antarctic fur seals

Immune defenses are crucial for survival but costly to develop and maintain. Increased immune investment is therefore hypothesized to trade-off with other life-history traits. Here, we examined innate and adaptive immune responses to environmental heterogeneity in wild Antarctic fur seals. In a fully crossed, repeated measures design, we sampled 100 pups and their mothers from colonies of contrasting density during seasons of contrasting food availability. Biometric and cortisol data as well as blood for the analysis of 13 immune and oxidative status markers were collected at two key life-history stages. We show that immune responses of pups are more responsive than adults to variation in food availability, but not population density, and are modulated by cortisol and condition. Immune investment is associated with different oxidative status markers in pups and mothers. Our results suggest that early life stages show greater sensitivity to extrinsic and intrinsic effectors, and that immunity may be a strong target for natural selection even in low-pathogen environments such as Antarctica.

The Effect of Using Aqueous Extract of Cyperus Rotundus Tubers on Characteristics and Shelf Life of Chicken Nuggets

The experiment was conducted to investigate the effect of the aqueous extract of the Cyperus ‎rotundus tubers ‎on fat oxidation and stored frozen chicken nuggets' physical and microbial ‎characteristics. The extract was incorporated into minced poultry meat at concentrations of 0% (control), 0.1%, 0.2%, 0.3%, and 0.4%, and the treated samples were stored for periods of 1 and 30 days at -18°C. The addition of Cyperus rotundus extract significantly improved the pH values and water-holding capacity of the treated nuggets (T2, T3, T4, and T5) compared to the control (T1) across both storage durations. Moreover, a notable reduction in lipid oxidation markers (peroxide value (PV), thiobarbituric acid reactive substances (TBA), free fatty acids (FFA), and total volatile nitrogen (TVN) was observed in the treated samples relative to the control. Additionally, a significant decrease in the total coliform bacteria count was evident in the treated nuggets, which inversely correlated with the concentration of the Cyperus rotundus extract. The findings suggest that the aqueous extract of Cyperus rotundus tubers beneficially affects the quality and safety of chicken nuggets, enhancing their shelf life when stored at -18°C for up to 30 days‎‎‎.

Nutritional load in post-prandial oxidative stress and the pathogeneses of diabetes mellitus

Diabetes mellitus affected more than 500 million of people globally, with an annual mortality of 1.5 million directly attributable to diabetic complications. Oxidative stress, in particularly in post-prandial state, plays a vital role in the pathogenesis of the diabetic complications. However, oxidative status marker is generally poorly characterized and their mechanisms of action are not well understood. In this work, we proposed a new framework for deep characterization of oxidative stress in erythrocytes (and in urine) using home-built micro-scale NMR system. The dynamic of post-prandial oxidative status (against a wide variety of nutritional load) in individual was assessed based on the proposed oxidative status of the red blood cells, with respect to the traditional risk-factors such as urinary isoprostane, reveals new insights into our understanding of diabetes. This new method can be potentially important in drafting guidelines for sub-stratification of diabetes mellitus for clinical care and management.

TRPV1/cPLA2/AA pathway contributes to ferroptosis-mediated acute liver injury in heatstroke

With the increasing frequency of global heatwaves, the incidence of heatstroke (HS) is significantly rising. The liver plays a crucial role in metabolism and is an organ highly sensitive to temperature. Acute liver injury (ALI) frequently occurs in patients with HS, yet the exact mechanisms driving ALI in HS are still unknown. In this basic study, we investigated the specific molecular mechanisms by which cytosolic phospholipase A2 (cPLA2) mediates ferroptosis, contributing to the development of ALI following HS. We utilized a mouse model of HS and divided the mice into healthy control and HS groups for a series of experiments. Firstly, we assessed oxidative damage markers in tissues and cells, as well as ferroptosis biomarkers. Additionally, we conducted a non-targeted metabolomics analysis to validate the role of key enzymes in metabolism and the ferroptosis pathway. Our results indicated that ferroptosis contributed to the progression of ALI after HS. Administering the ferroptosis inhibitor liproxstatin-1 (10 mg/kg) post-HS onset significantly inhibits HS-induced ALI progression. Mechanistically, heatstroke triggered cPLA2 activation and increased the levels of its metabolic product, arachidonic acid, thereby further promoted the occurrence of ferroptosis. Furthermore, heatstroke mediated cPLA2 activation might involve enhancing transient receptor potential vanilloid subtype 1 (TRPV1) receptor function. Overall, these results highlighted the critical role that cPLA2-mediated ferroptosis plays in the development of ALI following HS, indicating that inhibiting cPLA2 may present a novel therapeutic approach to prevent ALI after HS by limiting liver cell death.

The potential liver injury induced by metronidazole-provoked disturbance of gut microbiota: modulatory effect of turmeric supplementation.

It has been reported that the gut-liver axis and intestinal microbiome contribute crucially to different liver diseases. So, targeting this hepato-intestinal connection may provide a novel treatment modality for hepatic disorders such as drug-induced liver injury (DILI). The present study thought to investigate the protective effect of turmeric (TUR) on metronidazole (MNZ)-induced liver damage and the possible association of the gut-liver axis and gut microbiota as a suggested underlying mechanism. In the first experiment, a MNZ-induced liver injury rat model was reproduced after 130mg/kg oralMNZ administration for 30days. Meanwhile, the treatment group was orallytreated with 100mg/kg turmeric daily. In the second experiment, fecal microbiome transplantation (FMT) was conducted, in which the fecal microbiome of each group in the first experiment was transplanted to a healthy corresponding group in the second experiment. The liver enzymes (aminotransferase (ALT) and aspartate aminotransferase (AST)) and histopathological examination were estimated to assess liver function. Inflammatory cytokines and oxidative markers were evaluated in the liver tissues. Histological analysis, intestinal barrier markers, and expression of tight junction proteins were measured for assessment of the intestinal injury. Changes in the gut microbial community and possible hepatic bacterial transmission were analyzed using 16S rRNA sequencing. MNZ induced intestinal and liver injuries which were significantly improved by turmeric. Increased firmicutes/bacteroidetes ratio and bacterial transmission due to gut barrier disruption were suggested. Moreover, TUR has maintained the gut microbial community by rebalancing and restoring bacterial proportions and abundance, thereby repairing the gut mucosal barrier and suppressing bacterial translocation. TUR protected against MNZ-induced gut barrier disruption. Reshaping of the intestinal bacterial composition and prohibition of the hepatic microbial translocation were suggested turmeric effects, potentially mitigating MNZ-related liver toxicity.

Impact of Pediococcus pentosaceus YF01 on the exercise capacity of mice through the regulation of oxidative stress and alteration of gut microbiota.

Using treadmill training, this study replicated human exercise conditions and triggered exercise-induced fatigue in mice to examine the potential of Pediococcus pentosaceus YF01 in delaying this fatigue by regulating oxidative stress and its impact on the exercise capacity and gut microbiota of mice. The exercise capacity of mice was tested by conducting exhaustion tests, determining histopathological changes in mouse tissues, detecting the levels of serum biochemical markers, and evaluating the mRNA expression levels of relevant genes. YF01 prolonged the exhaustion time of mice, increased the serum levels of oxidative stress-related markers T-AOC, CAT, and GSH, as well as GLU and LA levels in the mice. YF01 decreased the levels of hepatic-related markers AST and ALT, as well as exercise-related markers LDH, BUN, UA, and CRE in the mice. YF01 upregulated the mRNA expression of MyHc I, SIRT1, and PGC in muscle tissues, as well as SOD1, SOD2, and CAT in both liver and muscle tissues. YF01 also downregulated the mRNA expression of MyHc IIa, MyHc IIb, and MyHc IIx in muscle tissues. Furthermore, YF01 increased the abundance of beneficial bacteria such as Lactobacillus and Lachnospiraceae in the gut microbiota of mice. In conclusion, P. pentosaceus YF01 may affect the exercise capacity of mice by modulating oxidative stress levels, thereby offering novel ideas for developing of sports science and human health.

Pre-mating exposure with hesperidin protects N-ethyl-N-nitrosourea-induced neurotoxicity and congenital abnormalities in next generation of mice as a model of glioma.

Chemical carcinogen-induced oxidative stress has a key role in cell signaling linked to the development of cancer. Oxidative stress leads to oxidative damage to cellular membranes, proteins, chromosomes and genetic material. It is thought that compounds like hesperidin with high antioxidant and anticancer potential can reduce development of cancer induced by chemical carcinogens via neutralizing their oxidative damages. We investigated protective effect of hesperidin against N-Ethyl-N-Nitrosourea (ENU)-induced neurotoxicity, congenital abnormalities and possible brain cancer after exposure of mice during pregnancy as model of glioma. The mice were divided to four groups; control (normal saline), ENU (40mg/kg daily for three consecutive days from the 17th to the 19th of pregnancy), hesperidin (pretreated with 25mg/kg for 30 consecutive days, before mating) + ENU and hesperidin alone. Developmental toxicity parameters (the number of pregnant mice, stillbirths, abortion, live and dead offspring), behavioral tests (novel object recognition, open field and elevated plus maze) were performed. Moreover, the activity of butrylcholinesterase and acetylcholinesterase enzymes, oxidative markers and histopathological abnormalities were detected in brain tissue. Our data showed that conversely, the pretreatment of hesperidin reduces various degrees of developmental toxicity, neurobehavioral dysfunction, neurotoxicity, oxidative stress and histopathological abnormalities induced by ENU as a neurotoxic and carcinogenic agent in the next generation. In conclusion, pre-mating exposure with hesperidin may open new avenues for prevention of primary brain cancer in next generation and could be valuable for enhancing the antioxidant defense and minimizing the developmental and neurotoxicity of DNA alkylating agents.

Impact of Soluble and Exchangeable Concentrations of Elements in Surface Sediments from Recreational Areas on Culturable Bacterial Behaviors

Contamination of major and trace elements in sediments is a global concern due to their potential risks to organisms. Bacteria also play vital roles in ecosystem processes and human health. However, the environmental adaptation of bacterial species due to human activities remains unclear. Therefore, in this study, surface sediments were collected from 12 recreational areas in Istanbul, Türkiye. Major and trace elements were determined in soluble and exchangeable fractions of sediments using inductively coupled plasma–optical emission spectrometry (ICP-OES). In addition, viability and primary biochemical and oxidative markers (protein, antioxidant, and lipid peroxidase) of gram-positive Staphylococcus aureus and gram-negative Pseudomonas aeruginosa were assessed with exposure to soluble and exchangeable fractions of sediments from 1 to 42 h. The results showed that Na, Mg, K, Ca, P, Fe, Cu, Mn, Zn, and Al were present at average concentrations of 1254.1 ± 574.5, 234857.0 ± 126335.7, 109960.3 ± 73248.6, 201343.0 ± 84426.4, 124.0 ± 77.1, 129.5 ± 82.4, 36.0 ± 22.8, 25.2 ± 32.8, 26.3 ± 16.4, and 186.5 ± 76.7 mg/kg, respectively. The bacterial responses to the soluble and exchangeable fractions of sediments showed that approximately 27% of Staphylococcus aureus exhibited inhibition at short exposures; the inhibition levels were 14% to 34% for Pseudomonas aeruginosa. However, the inhibition decreased and no specific viability changes were observed at longer exposures compared to controls. The viability of bacteria is explained by the protein, antioxidant and lipid peroxidation with moderate and strong correlations. The bacterial responses were evaluated using elemental concentrations, and adaptation was explained by the correlation results.

Safety and efficacy indicators of guarana and Brazil nut extract carried in nanoparticles of coenzyme Q10: Evidence from human blood cells and red earthworm experimental model

This study characterized a nanosupplement based on coenzyme Q10 containing guarana (Paullinia cupana) and Brazil nuts oil (Bertholetia excelsa) (G-Nut). Determined cytotoxic and oxi-immunomodulatory effects on human peripheral blood mononuclear cells (PBMCs) and its effect on mortality of red Californian earthworms (Eisenia fetida) and on the immune efficiency of its coelomocytes immune by in vitro exposure to yeast dead microorganism. The cytotoxic and immunomodulatory effects of G-Nut and the GN-Free extract (0.25–3 mg/mL) were determined in PBMC cultures. Apoptotic, oxidative, and inflammatory markers were determined using biochemical, immunological, and molecular protocols. The effects of G-Nut and GN-Free extracts on mortality and immune efficiency were investigated in earthworms. G-Nut and GN-Free did not induce cytotoxic events in PBMCs, triggering the decrease in apoptotic (caspases 3 and 8) gene expression, lipid and protein oxidation levels, or pro-inflammatory cytokine levels. G-Nut and GN-Free did not trigger earthworm mortality and improved coelomocyte immune efficiency by increasing Eisenia neutrophil extracellular DNA traps and brown body formation when exposed to dead yeasts. The G-Nut nanoformulation is safe and can be used as a new form of food supplement by oral or transdermal delivery.

PERFORMANCE AND MEAT QUALITY OF BROILER CHICKEN FED GRADED LEVELS OF BLACK COFFEE SEED (COFFEE ARABICA) POWDER SUPPLEMENTED DIET

Oxidative degradation is a deleterious condition that affects quality of meat, thereby poses a threat to poultry industry. However, this can be mitigated through feeding with antioxidants, therefore the need for inclusion of high antioxidant compound, such as coffee, in poultry diet. One-day old Ross 308 chicks (n = 200; r = 5) were randomly allotted to four diets containing black coffee seed powder (BCSP): 0.0 g/kg; 1.25 g/kg; 2.50 g/kg and 3.75 g/kg. Birds were fed ad libitum with free access to water for 6 weeks. Total weight gain (TWG) (g/b), total feed intake (TFI) (g), feed conversion ratio (FCR), haematology, oxidative markers, gut microbiology (x105cfu/mL) of birds, sensory characteristics (9-point hedonic scale) and total volatile nitrogen base (TVB-N) (mg/100 g) of broiler meats were assessed. Data were analyzed using ANOVA at P = 0.05. No significant differences in TWG (1873.12 − 1927.58) and FCR (1.55 − 1.71) were observed. However, TFI at 3.75 g/kg of BCSP (3216) was higher (P &lt; 0.05) than at 0 g/kg (3090), 1.25 g/kg 2967 and 2.50 g/kg of BCSP (3072) in the bird diet. Haemoglobin (12.60) at 1.25 g/kg BCSP was higher (P &lt; 0.05) than at 0 g/kg BCSP (10.83), but similar to the groups of 2.50 g/kg (10.97) and 3.75 g/kg (12.13) BCSP in the diet. Creatinine (0.97mg/dL) in the 1.25 g/kg BCSP group was higher (P &lt; 0.05) than those in the 0 g/kg (0.68 mg/dL) and 3.75 g/kg (0.60 mg/dL) groups but similar to the 2.50 g/kg group (0.88 mg/dL). No significant differences in almost all the oxidative markers were recorded. Gut microbiology showed that heterophilic (11.60), Coliform (8.30) and E.coli (13.70) contents in the 0/kg BCSP group were higher (P &lt; 0.05) than those in the 1.25 g/kg group (9.00, 5.58 and 4.48), the 2.50 g/kg group (3.55, 1.83 and 1.28) and 3.75 g/kg group (3.30, 0.53 and 0.25) for heterophilic, coliform and E. coli respectively. Lactobacillus in the 3.75 g/kg group (7.53) was higher (P &lt; 0.05) than that in the 2.50 g/kg (5.63), the 1.25 g/kg (5.70) and 0 g/kg (1.58) groups. With the increase of BCSP inclusion, the TVB-N decreased; aroma and taste of BCSP meat were best and well accepted. Low pathogenic gut microorganisms and total volatile nitrogen base coupled with high sensory acceptability of meat confirm the antioxidant potential of black coffee in broiler chicken diet.

Mifepristone protects acetaminophen induced liver injury through NRF2/GSH/GST mediated ferroptosis suppression

Ferroptosis is a form of iron-dependent cell death that has attracted significant attention for its potential role in numerous diseases. Targeted inhibition of ferroptosis could be of potential use in treating diseases: such as drug induced liver injury (DILI). Ferroptosis can be antagonized by the xCT/GSH/GPX4, FSP1/CoQ10, DHODH/CoQ10, GCH1/BH4, and NRF2 pathways. Identifying novel anti-ferroptosis pathways will further promote our understanding of the biological nature of ferroptosis and help discover new drugs targeting ferroptosis related human diseases. In this study, we identified the clinically used drug mifepristone (RU486) as a novel ferroptosis inhibitor. Mechanistically, RU486 inhibits ferroptosis by inducing GSH synthesis pathway, which supplies GSH for glutathione-S-transferase (GST) mediated 4-HNE detoxification. Furthermore, RU486 induced RLIP76 and MRP1 export 4-HNE conjugate contributes to its anti-ferroptosis activity. Interestingly, RU486 induced GSH/GSTs/RLIP76&MRP1 anti-ferroptosis pathway acts independent of classic anti-ferroptosis systems: including xCT/GSH/GPX4, FSP1, DHODH, GCH1, SCD1 and FTH1. Moreover, NRF2 was identified to be important for RU486's anti-ferroptosis activity by inducing downstream gene expression. Importantly, in mouse model, RU486 showed strong protection effect on acetaminophen (APAP)-induced acute liver injury, evidenced by decreased ALT, AST level and histological recovery after APAP treatment. Interestingly, RU486 also decreased oxidative markers, including 4-HNE and MDA, and induced NRF2 activation as well as GSTs, MRP1 expression. Together, these data suggest NRF2/GSH/GST/RLIP76&MRP1 mediated detoxification pathway as an important independent anti-ferroptosis pathway act both in vitro and in vivo.