Levels Of Oxidative Stress Markers Research Articles

Association of serum levels of inflammation and oxidative stress markers with cognitive outcomes in multiple sclerosis; a systematic review.

Multiple sclerosis (MS) is an immune-mediated disease with cognitive impairment being a crucial manifestation. Oxidative stress and inflammation play significant roles in the disease's pathogenesis. This systematic review explores the association between inflammation and oxidative stress markers, with cognitive outcomes in MS patients. This study adhered to the Joanna Briggs Institute (JBI) and PRISMA 2020 methods. Eligibility criteria included studies with MS patients, evaluating serum inflammation and/or oxidative stress markers, assessing cognitive function, and examining the relationship between these factors. PubMed, Scopus, Embase, and Web of Science, were searched and the risk of bias was assessed using the JBI checklists. Out of 1609 identified records, 10 studies were included in this systematic review. The studies were published between 2006 and 2023 and involved 629 MS patients. Current evidence suggests a negative correlation between TNF-α, and cognitive outcomes in MS (reported in three out of five studies). Associations between the decreased native and total thiol levels, as well as interleukin (IL)-17A with cognitive impairment, and the correlation between IL-6 and C-reactive protein (CRP) with cognitive scores in MS are also reported (one study for each). IL-10 (four studies), glutathione peroxidase (GPX), reduced glutathione (GSH), catalase activity (CAT), ischemia-modified albumin (IMA), IL-8, IL-18, and IL-2 (one study for each) did not found to be associated with cognition in MS and evidence regarding the possible role of interferon-gamma (IFN-γ), total antioxidant capacity (TAC), and malondialdehyde (MDA) is not definitive. The review findings suggest a complex association between oxidative stress and inflammation with cognitive outcomes in MS. Diversity in study designs, participant characteristics, and assessment methods makes the findings of this study inconclusive and highlights the need for future research.

Afobazole alleviates streptozotocin-induced diabetic nephropathy in rats via hypoglycemic, antioxidant, anti-inflammatory, and anti-apoptotic properties: Role of the S1R/Nrf2 antioxidant axis.

Sigma-1 receptor (S1R) activation was recently identified as a promising target for preventing diabetic nephropathy (DN) by mitigating hypoxia, oxidative stress, and inflammation. This study aimed to investigate the potential reno-protective effect of the S1R agonist afobazole against streptozotocin (STZ)-induced DN in rats compared to metformin. Rats were split into six groups: the normal control group; the diabetic control group received STZ (55mg/kg i.p.); the other four groups received STZ and were treated with different doses of either afobazole (10, 15, and 20mg/kg) or metformin (200mg/kg). Metabolic parameters and renal function were assessed. Expression levels of oxidative stress markers and inflammatory cytokines were measured using ELISA, apoptosis-related proteins were evaluated using immunohistochemistry, and gene expression of S1R, Nrf2, NF-κB, and TLR-4 was determined. Histopathological analysis was performed on kidney tissues. Both afobazole and metformin exerted hypoglycemic effects, alleviating renal injury, reducing blood urea nitrogen (BUN) and serum creatinine, and restoring oxidant/antioxidant balance in diabetic rats. Both treatments boosted renal S1R and Nrf2 levels, suppressed inflammatory proteins and cytokines, and reduced apoptotic features. The study revealed that afobazole provided nephroprotection in STZ-induced DN through a hypoglycemic, antioxidant, anti-inflammatory, and anti-apoptotic potential mediated by activating the S1R/Nrf2 antioxidant axis. The 15mg/kg dose elicited the most pronounced nephroprotective effects, outperforming other treatment groups.

Farnesol Inhibits Cell Viability and Activates Apoptosis in Glioma C6 Cells via Downregulating Phosphoinositide 3-kinase (PI3K)/Protein Kinase B (AKT)/Mammalian Target of Rapamycin (mTOR) Pathway

Background Gliomas are the most aggressive and devastating brain tumors, with a poor prognosis due to their complex etiology, diverse clinical manifestations, and the limited efficacy of existing treatment methods. Purpose The present work was conducted to understand the anticancer activities of farnesol against glioma C6 cells. Methods The effects of farnesol on in vitro free radical scavenging were evaluated at various dosages (1–100 µM). A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was used to assess the influence of farnesol on the growth of glioma C6 cells and nonmalignant Vero cells. The apoptotic levels in the cells were investigated using 4′,6-diamidino-2-phenylindole (DAPI) and dual staining assays. The levels of oxidative stress markers, inflammatory biomarkers, apoptotic protein levels, and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway proteins were assessed using the respective test kits. Results The results of the free radical scavenging assays proved the antioxidant properties of farnesol. The MTT assay findings demonstrated a significant reduction in C6 cell viability following treatment with farnesol. The findings of the fluorescent assays proved the onset of apoptosis in the farnesol-treated C6 cells. Furthermore, the farnesol treatment effectively increased oxidative stress, increased apoptotic protein levels, and reduced inflammatory marker levels in the C6 glioma cells. The PI3K, AKT, and mTOR protein expression were also successfully downregulated in the C6 glioma cells by farnesol. Conclusion The current results demonstrate that farnesol effectively suppresses viability and triggers apoptosis in C6 cells. Thus, it has the capacity to be an effective anticancer agent to treat glioma. Nonetheless, additional work is still necessary in the future to determine the specific molecular mechanisms involved in farnesol-induced apoptosis in C6 cells.

Blackcurrant (Ribes nigrum L.) and Its Association with Donepezil Restore Cognitive Impairment, Suppress Oxidative Stress and Pro-inflammatory Responses, and Improve Purinergic Signaling in a Scopolamine-Induced Amnesia Model in Mice.

Purinergic signaling plays a major role in aging and neurodegenerative diseases, which are associated with memory decline. Blackcurrant (BC), an anthocyanin-rich berry, is renowned for its antioxidant and neuroprotective activities. However, evidence on the effects of BC on purinergic signaling is lacking. This study investigated the effects of BC and its association with Donepezil (DNPZ) on learning and memory, on the modulation of purinergic signaling, pro-inflammatory responses, and oxidative markers in a mouse model of cognitive impairment chronically induced by scopolamine (SCO). Animals were divided into twelve groups and treated with BC (50 or 100mg/kg), and/or DNPZ (5mg/kg), and/or SCO (1mg/kg). Results showed that SCO decreased spatial learning and memory as assessed by the Morris Water Maze test, and treatment with BC and/or DNPZ restored these effects. Furthermore, BC and/or DNPZ treatments also prevented changes in ecto-nucleoside triphosphate diphosphohydrolase (NTPDase) and adenosine deaminase (ADA) activities and restored the increased density of P2X7 and A2A receptors in synaptosomes of the cerebral cortex of SCO-induced mice. Moreover, the increased Nod-like receptor protein 3 (NLRP3) and interleukin-1β expression, and the oxidative stress markers levels were reduced by BC and/or DNPZ treatments, compared with the SCO group. Overall, BC and/or DNPZ treatments ameliorated SCO-induced cognitive decline, alleviated oxidative stress and pro-inflammatory responses, and improved purinergic signaling. These findings underscore the potential of BC, especially when in combination with DNPZ, as a therapeutic agent for the prevention of memory deficits associated with aging or neurological diseases.

Evaluation of the therapeutic effects of nebulized inhalation of hydrogen-rich water on primary blast lung injury in C57BL/6 mice.

Primary blast lung injury is a common and severe consequence of explosion events, characterized by immediate and delayed effects such as apnea and rapid shallow breathing. The overpressure generated by blasts leads to alveolar and capillary damage, resulting in ventilation-perfusion mismatch and increased intrapulmonary shunting. This reduces the effective gas exchange area, causing hypoxemia and hypercapnia. Hydrogen (H2), a small-molecular-weight, nonpolar diatomic molecule, has shown potential in treating various diseases due to its antioxidant and anti-inflammatory properties. This study evaluates the therapeutic effects of nebulized hydrogen-rich water on primary blast lung injury in C57BL/6 mice and explores the underlying mechanisms. C57BL/6 mice (n= 150), aged 6-8weeks, were randomly divided into 2 groups: the blast injury control group (n= 75) and the nebulized hydrogen-rich water treatment group (n= 75). Mice were exposed to a blast overpressure of 266±9.156 kPA and treated with either nebulized hydrogen-rich water or sterile injection water immediately postinjury. Observations were made at 6, 12, 24, and 48hours postinjury. Lung function was assessed using whole-body plethysmography, and arterial blood gases were analyzed. Lung tissue was examined histologically and biochemically for markers of inflammation and oxidative stress. The survival rates at different time points postinjury in the nebulized hydrogen-rich water treatment group were significantly higher than those in the blast injury control group (6hours postinjury: 89.3% vs 78.6%; 12hours postinjury: 81.3% vs 72%; 24hours postinjury: 81.3% vs 61.3%, P < .01). Lung function tests revealed significant improvements in tidal volume (12hours postinjury: 0.11±0.018 vs 0.08±0.016, 24hours postinjury: 0.16±0.013 vs 0.12±0.013, 48hours postinjury: 0.18±0.02 vs 0.13±0.014), respiratory rate (6hours postinjury: 235.07±12.82 vs 268.29±13.73; 12hours postinjury: 265.47±10.06 vs 342.16±16.34; 24hours postinjury: 248.20±9.28 vs 352.80±15.99; 48hours postinjury: 226.12±15.81 vs 318.18±15.81), and minute ventilation (12hours postinjury: 22.05±3.46 vs 15.93±3.68; 24hours postinjury: 27.30±2.15 vs 21.62±2.48; 48hours postinjury: 37.48±3.93 vs 28.32±2.98) in the nebulized hydrogen-rich water treatment group (P < .01). Arterial blood gas analysis indicated better oxygenation and reduced hypercapnia in the nebulized hydrogen-rich water treatment group (P < .05). Histologic examination showed reduced lung edema and hemorrhage in the nebulized hydrogen-rich water treatment group. Levels of inflammatory cytokines (interleukin-1β, interleukin-6, and tumor necrosis factor α) and oxidative stress markers (ie, malondialdehyde) were significantly lower, whereas antioxidant enzyme (total superoxide dismutase) activity was higher in the nebulized hydrogen-rich water treatment group compared with the blast injury control group (P < .01). Arterial blood gas analysis indicated better oxygenation and reduced hypercapnia in the nebulized hydrogen-rich water treatment group (P < .05). Histologic examination showed reduced lung edema and hemorrhage in the nebulized hydrogen-rich water treatment group. Levels of inflammatory cytokines (interleukin-1β, interleukin-6, and tumor necrosis factor α) and oxidative stress markers (ie, malondialdehyde) were significantly lower, whereas antioxidant enzyme (total superoxide dismutase) activity was higher in the nebulized hydrogen-rich water treatment group compared with the blast injury control group (P < .01). Hydrogen-rich water treatment significantly improves survival rates and lung function and reduces inflammation and oxidative stress in mice with primary blast lung injury. These findings suggest that hydrogen's antioxidant and anti-inflammatory properties play a crucial role in mitigating lung damage and improving respiratory function postinjury. Further long-term studies and imaging analyses are needed to confirm these findings and elucidate the molecular mechanisms involved. This study provides a theoretical basis for the clinical application of hydrogen-rich water in treating blast-induced lung injuries.

Tocilizumab alleviated lipopolysaccharide-induced acute lung injury by improving PI3K/AKT pathway.

Acute lung injury (ALI) is a severe inflammatory condition of the respiratory system, associated with high morbidity and mortality. This study investigates the therapeutic potential of tocilizumab (TZ), an IL-6 receptor inhibitor, in mitigating lipopolysaccharide (LPS)-induced ALI by modulating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway. An ALI model was established using LPS induction. Lung damage was assessed by hematoxylin-eosin (H&E) staining, alongside measurements of respiratory function, including PaO2/Fio2 ratios, lung edema, airway resistance, and lung compliance. Western blotting analyzed the expression of phosphorylated PI3K and AKT (P-PI3K, P-AKT), while ELISA quantified levels of TNF-α, IL-1β, IL-6, and oxidative stress markers. Apoptosis was evaluated using the TUNEL assay, and key apoptotic proteins (Bcl-2, Bax, and caspase-3) were measured by Western blotting. The Cell Counting Kit-8 (CCK-8) assay was employed to determine cell viability. The LPS-induced model exhibited decreased P-PI3K and P-AKT levels, while TZ treatment significantly elevated these markers. TZ also reduced lung tissue damage, improved respiratory function, and decreased inflammation, oxidative stress, and apoptosis. However, co-administration with LY294002 (a PI3K inhibitor) blocked these benefits, reversing the protective effects of TZ. TZ alleviates lung injury and improves outcomes in LPS-induced ALI by enhancing the PI3K/AKT pathway.

The Functional Identification of the CYP2E1 Gene in the Kidney of Lepus yarkandensis.

This study aims to identify the function of the cytochrome P450 2E1 (CYP2E1) gene in the kidneys of Lepus yarkandensis. CYP2E1 is a significant metabolic enzyme involved in the metabolism of various endogenous and exogenous compounds and is associated with the occurrence and progression of multiple diseases. Given L. yarkandensis's ability to survive in the extremely arid L. yarkandensis, we hypothesize that CYP2E1 in its kidneys plays a crucial role in adaptability. Through molecular cloning and sequence analysis, we discovered that the CYP2E1 gene of Lepus yarkandensis encodes a protein of 493 amino acids. The 493-amino acid protein encoded by the Lepus yarkandensis CYP2E1 gene shows 13 amino acid variation sites compared to the homologous protein in Oryctolagus cuniculus. The protein is primarily localized to the endoplasmic reticulum membrane and lacks transmembrane structures. In the yeast expression system, the heterologous expression of the CYP2E1 gene enhanced the yeast's tolerance to drought, salinity, and high temperatures, achieved by increasing antioxidant enzyme activity and reducing levels of oxidative stress markers. Additionally, this study identified a "Yeast Oxidative Stress Lethal Threshold (Yeast OSLT)" under specific stress conditions. Once this threshold is exceeded, the cell's antioxidant defense system can no longer maintain cellular homeostasis, leading to massive cell death. Although CYP2E1 did not change this threshold, it contributed to cell survival to some extent. These findings not only reveal the function of L. yarkandensis CYP2E1 in stress adaptation but also provide valuable molecular insights into its survival strategy in extreme environments.

The profile of oxidative stress markers (arachidonic and linoleic acid derivatives) in patients with benign prostatic hyperplasia in relation to metabolic syndrome.

So far, it has been proven that benign prostatic hyperplasia (BPH) is strongly associated with inflammation resulting from, i.a. the presence of infectious agent, autoimmune disease, aging process and lipid disorders associated with metabolic syndrome (MetS). We analyzed the association between serum eicosanoides (HETE, HODE, lipoxins, prostaglandin, and leucotrien) in aging man with benign prostatic hyperplasia (BPH) and healthy controls. The study involved 219 men (with BPH, n = 144; healthy controls, n = 75). We assessed the content arachidonic and linoleic acid derivatives in the serum samples of the study participants using liquid chromatography (HPLC). The levels of: RvE1 (p < 0.001); LXA4 5S,6R,15R (p = 0.001); 10S,17R-DiDHA (p < 0.001); MaR1 (p = 0.002); 9S-HODE (p < 0.05); 15S-HETE (p < 0.05); 12S-HETE (p < 0.001); 5-oxoETE (p < 0.05) and 5-HETE (p < 0.001) were significantly higher in patients with BPH than in the control group. PGE2 (p = 0.007), LTB4 (p < 0.001), and 18RS-HEPE (p < 0.001) were significantly higher in control group. We also analyzed the relationship between LXA4 5S,6R,15R serum levels of oxidative stress markers and concomitance of MetS. We noticed a relationship between levels and MetS (F1216 = 6.114965, p = 0.01). Our research results suggest that pro-inflammatory mediators and suppressors of inflammation are involved in the development of BPH, but their exact contribution has yet to be investigated.

α-Bisabolol alleviates diesel exhaust particle-induced lung injury and mitochondrial dysfunction by regulating inflammatory, oxidative stress, and apoptotic biomarkers through the c-Jun N-terminal kinase signaling pathway.

Exposure to particulate matter ≤2.5μm in diameter (PM2.5) is associated with adverse respiratory outcomes, including alterations to lung morphology and function. These associations were reported even at concentrations lower than the current annual limit of PM2.5. Inhalation of PM2.5, of which diesel exhaust particles (DEPs) is a major component, induces lung inflammation and oxidative stress. α-Bisabolol (BIS) is a bioactive dietary phytochemical with various pharmacological properties, including anti-inflammatory and antioxidant actions. Here, we evaluated the possible protective effects of BIS on DEP-induced lung injury. Mice were exposed to DEPs (20 µg/mouse) or saline (control) by intratracheal instillation. BIS was administered orally at two doses (25 and 50mg/kg) approximately 1h before DEP exposure. Twenty-fourhours after DEP administration, multiple respiratory endpoints were evaluated. BIS administration was observed to prevent DEP-induced airway hyperreactivity to methacholine; influx of macrophages, neutrophils, and lymphocytes in the bronchoalveolar lavage fluid; and increases in epithelial and endothelial permeabilities. DEP exposure caused increases in the levels of myeloperoxidase, proinflammatory cytokines, and oxidative stress markers in lung tissue homogenates, and all these effects were abated by BIS treatment. The activities of mitochondrial complexes I, II, III, and IV were markedly increased in the lungs of mice exposed to DEPs, and these effects were significantly reduced in the BIS-treated group. Intratracheal instillation of DEPs induced DNA damage and increase in the apoptotic marker cleaved caspase-3. The latter effects were prevented in mice treated with BIS and exposed to DEPs. Moreover, BIS mitigated DEP-induced increase in the expression of phospho-c-Jun N-terminal kinase (JNK) in a dose-dependent manner. BIS markedly alleviated DEP-induced lung injury by regulating the inflammatory, oxidative stress, and apoptotic biomarkers through the JNK signaling pathway. Following additional studies, BIS may be considered as a plausible protective agent against inhaled-particle-induced pulmonary adverse effects.

EGR1 regulates oxidative stress and aldosterone production in adrenal cells and aldosterone-producing adenomas.

Aldosterone-producing adenomas (APAs) are a major cause of primary aldosteronism, a common form of endocrine hypertension. Here, we demonstrate that Early Growth Response 1 (EGR1) plays a dual role in adrenal cell biology, regulating both oxidative stress and aldosterone production. Using RNA sequencing of RSL3-treated human adrenal cells and spatial transcriptomics of adrenal glands from patients with primary aldosteronism, we identify EGR1 as a key gene associated with RSL3-related oxidative stress and APAs. We show that EGR1 silencing decreases oxidative stress and increases CYP11B2 gene expression and aldosterone production in adrenal cells, while its overexpression has the opposite effects. Notably, EGR1 expression is downregulated in APAs and aldosterone-producing micronodules compared to the adjacent adrenal cortex, which correlates in part with decreased levels of oxidative stress markers. The adrenal cortex of pigs with secondary hyperaldosteronism shows decreased immunostaining of EGR1 and a marker of oxidative stress, suggesting a potential link between EGR1 expression, oxidative stress levels, and adrenocortical function. These findings reveal a novel mechanism linking EGR1 to oxidative stress regulation and aldosterone production in adrenal cells, with potential implications for the pathogenesis of APAs and other adrenocortical tumors.

NMDA receptors antagonists alleviated the acute phase of traumatic brain injury.

Traumatic brain injury (TBI) is a significant cause of mortality and disability worldwide. TBI has been associated with factors such as oxidative stress, neuroinflammation, and apoptosis, which are believed to be mediated by the N-methyl-D-aspartate (NMDA)-type glutamate receptor. Two NMDA receptor antagonists, ketamine and memantine, have shown potential in mitigating the pathophysiological effects of TBI. To conduct the study, a controlled cortical impact model was used to induce TBI in rats. The rats with TBI were then divided into three groups: a group receiving only TBI, a group receiving TBI along with memantine, and a group receiving TBI along with ketamine. After 24 hr, the levels of oxidative stress markers (such as SOD, MDA, and total thiol) in the brain tissue were measured. Immunohistochemical staining was also performed seven days after TBI to assess the activation of glial cells and the TLR-4/NF-κB neuroinflammatory pathway. The results indicated that treatment with memantine led to a reduction in MDA levels and an increase in SOD and total thiol levels. Memantine also decreased astrogliosis and down-regulated the TLR-4/NF-κB pathway. On the other hand, ketamine increased the levels of anti-oxidant markers but did not significantly affect the MDA level. Additionally, ketamine decreased the expression of NF-κB seven days after TBI. The findings suggest that NMDA receptor antagonists, such as ketamine and memantine, may have therapeutic effects on TBI by inhibiting oxidative stress and inflammatory responses.

2-Ethylhexyl diphenyl phosphate induces lung oxidative stress and pyroptosis in chicks.

2-Ethylhexyl diphenyl phosphate (EHDPHP) is a widely used organophosphorus flame retardant and plasticizer easily released into the environment. Its biological toxicity is of great concern. The lung is considered a possible target organ for EHDPHP, but currently, there are limited studies on the biotoxicity of EHDPHP in poultry lungs. Therefore, the lungs were selected as the target organ to study the toxic effects of EHDPHP on chicks and their mechanisms of action. In this study, 7-day-old chicks were gavaged with different concentrations of EHDPHP, and lung samples were collected at 14, 28, and 42days after intragastric administration. Lung histopathological and ultrapathological changes were examined by paraffin section-HE staining and transmission electron microscopy. The levels of lung damage markers (LDH) and oxidative stress markers (GSH-Px, SOD, and MDA) were detected by applying the kit. In contrast, lung cell pyroptosis-related factors (NLRP3, ASC, NF-κB, Pro-Caspase-1, IL-18, and IL-1β) and inflammatory factors (IL-6 and TNF-α) were assessed by using the qRT-PCR, Western blot and ELISA techniques. The results showed that EHDPHP induced pathological morphological changes and elevated LDH content in chick lungs, decreased lung antioxidant enzymes (GSH-Px and SOD) activities, increased peroxidation product MDA content and up-regulated the expression levels of cellular pyroptosis factors (NLRP3, ASC, NF-κB, Pro-Caspase-1, IL-18, and IL-1β), and the synthesis and secretion of inflammatory factors (IL-6 and TNF-α) were promoted. The above changes were EHDPHP dose-dependent. The results indicated that EHDPHP induced oxidative stress in chick lungs, resulting in oxidative damage to the lungs, and, intriguingly, the cellular pyroptosis pathway was activated, which was also involved in the process of EHDPHP-induced inflammatory damage in chick lungs. The results of this study revealed for the first time the damaging effects and mechanisms of EHDPHP on chick lungs. Also, they provided a scientific basis for further exploring the mechanisms of toxicity damage, safe use, and pollution control of EHDPHP.

Network pharmacology-based strategy to reveal Acacetin against lipopolysaccharide-induced lung injury.

Acacetin, a flavonoid isolated from Agastache rugosa, exhibits diverse biological activities, such as anti-tumor, anti-inflammatory and antioxidant activities. Its role in treating Lipopolysaccharide (LPS)-induced acute lung injury (ALI) remains incompletely illuminated. To explore the potential molecular mechanisms of Acacetin in alleviating ALI. The network pharmacological approach was employed to screen the target genes and pathways of Acacetin. Lung injury was analyzed by Hematoxylin-Eosin (H&E) staining. Bronchoalveolar lavage fluid, serum and lung tissues were collected to detect the levels of proinflammatory cytokines and oxidative stress markers. Immunofluorescence and RT-qPCR experiments were used to observe the expression of CD45, COX2, Ly6G, and related-target proteins. In vitro, RAW264.7 macrophages were stimulated with LPS and treated with AMPK siRNA or an AMPK inhibitor Coumpound C to verify the role of AMPK/nuclear factor erythroid 2-related factor 2 (Nrf2)/high-mobility group box 1 (HMGB1) signaling in Acacetin-mediated alleviation of ALI. Network data revealed that Acacetin could regulate HMGB1, AMPK, Nrf2, and IL-6. In vivo, Acacetin reversed pathological damage and the release of inflammatory factors, and alleviated oxidative stress and immune cell infiltration in ALI development. Acacetin remarkably upregulated the expression of AMPK and Nrf2, accompanied by HMGB1 downregulation. In vitro, inhibiting AMPK reversed the effects of Acacetin in LPS-treated RAW264.7, due to inactivation of AMPK/Nrf2/HMGB1 pathway. The combination of network pharmacology and experimental studies revealed the role of Acacetin in improving ALI via the AMPK/Nrf2/HMGB1 signaling axis, which provided new insights into the treatment of ALI with Acacetin as a candidate drug.

Pterostilbene attenuates oxidative stress induced by hydrogen peroxide in MAC-T cells through activating PINK1/Parkin-mediated mitophagy

High‐producing dairy cows are susceptible to altered redox balance owing to their high secretion and strong metabolism during transition to lactation. Previously reports demonstrated that pterostilbene (PTE) alleviate hydrogen peroxide (H2O2)-induced oxidative damage. However, molecular mechanism underlying protective role of PTE in H2O2-elicited oxidative stress in bovine mammary epithelial cells (MAC-T cells) remains unclear. The aims of our research is to clarify the potential molecular mechanisms of PTE in H2O2-triggered oxidative damage. MAC-T cells were pre-treated with PTE (0, 10, 25 and 50 μM) for 12 h and then cultured with H2O2 (0, 100, 200, 400, 600, 800 and 1000 μM) for another 24 h. The results were interpreted by CCK8, western blot, and immunofluorescence assay. Results showed that PTE significantly attenuated H2O2-mediated reduction in T-AOC, SOD and GSH-Px activity. Mechanistic studies found that PTE restricted the H2O2-induced protein expression of HO-1, GPX4 and SOD1, and PTE reversed intracellular MDA and ROS generation and decreased the MMP in MAC-T cells. Moreover, H2O2 exposure markedly inhibited mitophagy, whereas PTE pre-treatment activated PINK1/Parkin-mediated mitophagy pathway, which further limited ROS production. Overall, PTE can be used to improve oxidative stress and as a novel antioxidant agent in dairy cows. Highlights PTE restored the levels of H2O2-induced oxidative stress markers (T-AOC, SOD, GSH-Px and MDA) in MAC-T cells. PTE effectively blocked the increase of protein expression (HO-1, SOD1 and GPX4) in H2O2-induced MAC-T cells. PTE remarkably decreased the accumulation of ROS and improved MMP in H2O2-induced MAC-T cells. PTE exerted a significant protective effect against oxidative stress injury by reducing the inhibition of H2O2 on mitophagy.

Allostatic Load and Oxidative Stress Markers in Women With Early- and Late-Onset Preeclampsia.

Allostatic load and oxidative stress (OS) markers differ in women with and without preeclampsia. However, there is no difference in allostatic load and OS markers between late-onset preeclampsia (L-OP) and early-onset preeclampsia (E-OP). This study aimed to compare the concentrations of allostatic load and OS markers in pregnant women with L-OP and E-OP. This was a comparative cross-sectional study. Women with single pregnancy and a diagnosis of preeclampsia were included. Women with multiple pregnancies and/or chronic hypertension were excluded. Group 1 included women with E-OP (n=16), Group 2 included women with L-OP (n=45), and Group 3 included women without preeclampsia (n=40). No statistical differences were found in maternal age, body mass index, or number of gestations. Arginase levels were higher in Group 1 compared to Group 2 (p = 0.04) and Group 1 compared to Group 3 (p = 0.01). Total antioxidative capacity was higher in Group 1 compared to Group 2 (p = 0.03) and Group 1 compared to Group 3 (p = 0.001). Malondialdehyde levels were higher in Group 1 compared to Group 2 (p = 0.001) and Group 1 compared to Group 3 (p = 0.001). Total sulfhydryl compounds were lower in Group 1 compared to Group 2 (p = 0.01) and Group 1 compared to Group 3 (p = 0.001). No differences were observed between study groups in allostatic load markers. Higher levels of OS markers were found in women with E-OP compared to women with L-OP and controls.

Limonin alleviates imiquimod-induced psoriasis-like skin inflammation in mice model by downregulating inflammatory responses.

Psoriasis is a chronic inflammatory condition affecting 1-2% of the global population. Phytomedicine, which uses plant-based compounds, is emerging as a promising approach to managing such inflammatory diseases. Limonin, a phytochemical found in citrus fruits and known for its bitter taste, possesses significant pharmacological properties. In this study, we evaluated the anti-psoriatic effects of limonin using a psoriasis-induced mice model. BALB/c mice were treated with imiquimod to induce psoriasis and then administered limonin at doses of 20 and 40 mg/kg/day for 6 days. Tacrolimus ointment served as a positive control. We assessed the hematological profile to determine limonin's impact on leukocytes in the psoriasis model. Additionally, histomorphometric analysis of ear and skin tissues was conducted to evaluate the therapeutic effects of limonin. We further investigated the antioxidant properties of limonin by measuring levels of antioxidants and oxidative stress markers. The anti-inflammatory effects were evaluated by quantifying inflammatory cytokines and signaling proteins. In vitro, the cytotoxicity and anti-inflammatory potential of limonin were assessed using murine macrophage RAW264.7 cells. Our findings showed that limonin significantly reduced leukocyte counts, decreased inflammatory cell infiltration, and improved skin histoarchitecture in psoriasis-induced mice. Limonin also effectively scavenged free radicals and reduced levels of inflammatory cytokines and proteins without causing cytotoxicity in RAW264.7 cells. Overall, our in vivo and in vitro results confirm that limonin is a potent anti-inflammatory agent that effectively ameliorates imiquimod-induced psoriasis.

Protective effects of naringenin against methamphetamine-induced cell death in dopaminergic SH-SY5Y cells

ABSTRACT Background: Methamphetamine is a psychoactive substance that competes with the dopamine transporter, disrupting its flow and storage. This can trigger oxidative stress, finally resulting in neural cell death. Due to the increasing prevalence of methamphetamine use, extensive research has been devoted to finding treatments that ameliorate its detrimental effects. Naringenin, a dietary flavonoid found in citrus fruits, has shown several neuroprotective and pharmacological properties. Objectives: This study was aimed to assess the protective effects of naringenin against methamphetamine-induced dopaminergic cell death. Methods: Before exposure to methamphetamine, human neuroblastomaSH-SY5Y cells were either pretreated or not treated (controls) with naringenin. Cell viability, level of oxidative stress markers, and expression of some genes involved in apoptosis and autophagy processes were then assessed using MTT, ROS, and MMP assays, and qRT-PCR and Western blotting techniques. Results: Naringenin pretreatment significantly enhanced cell viability following methamphetamine exposure (p < .01). It significantly decreased ROS levels (p < .001), preserved mitochondrial membrane potential, and moderated upregulation of apoptotic (CytC, Casp3, and Bax) and autophagic genes (Beclin-1, and LC-3) and down-regulation of Bcl-2 as an anti-apoptotic gene. Similar naringenin-mediated patterns were observed for cytochrome C and caspase 3 proteins. Conclusion: Naringenin administration can be considered for treating the neurotoxic effects of methamphetamine.

Effect of aqueous extract of Mondia whitei fruits on high sucrose-induced oxidative stress in Drosophila melanogaster

Background/Aim: High sugar intake plays an important role in oxidative stress, which has been linked to development of diseases like diabetes. In this study, the effect of aqueous extract of Mondia whitei (AEMW) fruits on high sucrose-induced oxidative stress in Drosophila melanogaster was investigated. Materials and Methods: Adult flies (1 – 3 days old) were exposed to graded doses of AEMW for 12 days to determine the safe dose. Based on this, new flies were grouped into 5 (n = 5; 40 flies per vial). Group 1 served as control and were fed with basal diet, and group 2 with basal diet containing 30% sucrose. Groups 3 and 4, in addition to diet containing 30 % sucrose, were exposed to 0.25 and 0.5 mg AEMW/g diet, respectively, and group 5 flies were exposed to diet containing 0.5 mg AEMW/g diet only. Treatment lasted for 7 days. Biochemical assays such as glucose level, markers of antioxidant and oxidative stress were carried out to assess the effect of high sucrose and/or AEMW on flies. Results: Doses of AEMW up to 0.5 mg/g diet was safe for the flies. High sucrose diet significantly (p &lt; 0.05) increased the level of glucose and oxidative stress markers, and reduced the levels of antioxidant parameters when compared to the control. These changes were prevented by the doses of AEMW. Conclusion: It can be concluded that AEMW possesses anti-hyperglycemic and antioxidant properties, and could be suggested to act against oxidative stress induced by high sucrose in fruit flies.

Ameliorating Effect of S-Allyl Cysteine (Black Garlic) on 6-OHDA Mediated Neurotoxicity in SH-SY5Y Cell Line

Therapeutic approaches based on isolated compounds derived from natural products are more common in preventing diseases involving inflammation and oxidative stress at present. S-allyl cysteine (SAC) is a promising garlic-derived organosulfur compound with many positive effects in cell models and living systems. SAC has biological activity in various fields, enclosing healing in learning and memory disorders, neurotrophic effects, and antioxidant activity. In this study, we purposed to identify the neuroprotective activity of SAC toward 6-OHDA-induced cell demise in the SH-SY5Ycell line. For this purpose, 6-OHDA-induced cytotoxicity, and biochemical, and gene expression changes were evaluated in SH-SY5Y cells. SH-SY5Y cells grown in cell culture were treated with SAC 24hours before and after 6-OHDA application. Then, cell viability, antioxidant parameters, and gene expressions were measured. Finally, immunofluorescence staining analysis was performed. Our results showed that SAC increased cell viability by 144% at 80µg/mL with pre-incubation (2hours). It was observed that antioxidant levels were significantly increased and oxidative stress marker levels were decreased in cells exposed to 6-OHDA after pre-treatment with SAC (p<0.05). SAC supplementation also suppressed the increase in pro-inflammation levels (TNF-α/IL1/IL8) caused by 6-OHDA (p < 0.05). While 8-OHdG and Nop10 expressions were observed at a mild level in SAC pretreatment depending on the dose, 8-OHdG, and Nop10 expressions were observed at a moderate level in SAC treatment after 6-OHDA application (p<0.05). Our findings demonstrate the positive effect of pretreatment with SAC on SH-SY5Y cells injured by 6-OHDA, suggesting that SAC may be beneficial for neuroprotection in regulating oxidative stress and neuronal survival in an in vitro model of Parkinson's disease.

Protective effects of insoluble dietary fiber from cereal bran against DSS-induced chronic colitis in mice: From inflammatory responses, oxidative stress, intestinal barrier, and gut microbiota.

Insoluble dietary fiber (IDF) is a crucial component of cereals, and IDF from cereal bran (IDF-CB) has been reported to have multiple biological activities. However, the effect of IDF-CB on chronic colitis remains underexplored. The study aimed to investigate the impact of IDFs from wheat bran (WBIDF), rice bran (RBIDF), millet bran (MBIDF) and oat bran (OBIDF) on chronic colitis induced by dextran sulfate sodium (DSS). Our findings demonstrated that IDFs-CB supplementation mitigated DSS-induced weight loss and reduced lesions in the colon and spleen. Levels of proinflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α) and oxidative stress markers (MPO, iNOS and MDA)were decreased, and anti-inflammatory cytokine (IL-10) and T-SOD activity were increased after IDF-CB inclusion. Furthermore, IDFs-CB restored intestinal barrier function by regulating gene expression (up-regulated Muc-2, ZO-1 and Occludin, and down-regulated Claudin-1 and Claudin-4). Additionally, we analyzed the gut microbiota and SCFAs composition. WBIDF, MBIDF and OBIDF inhibited the growth of Muribaculaceae_unclassified, Bacteroides and Parasutterella. Conversely, IDFs-CB promoted the growth of Candidatus_Saccharimonas and norank_f__norank_o__Clostridia_UCG-014. Notably, WBIDF enhanced the abundance of Allobaculum, while MBIDF and OBIDF increased the abundance of Lachnospiraceae_NK4A136. Moreover, supplementation with IDFs-CB significantly elevated certain SCFA concentrations-particularly acetic acid and isohexanoic acid. Our results suggested that IDF-CB effectively alleviated DSS-induced chronic colitis; among them，WBIDF exhibited superior efficacy followed by OBIDF，MBIDF，and RBIDF. This study provides a theoretical foundation for dietary recommendations for patients suffering from inflammatory bowel disease.