Measurement Of Malondialdehyde Research Articles

Minocycline alleviates lipopolysaccharide-induced cardiotoxicity by suppressing the NLRP3/Caspase-1 signaling pathway.

Minocycline (Min), as an antibiotic, possesses various beneficial properties such as anti-inflammatory, antioxidant, and anti-apoptotic effects. Despite these known qualities, the precise cardioprotective effect and mechanism of Min in protecting against sepsis-induced cardiotoxicity (SIC) remain unspecified. To address this, our study sought to assess the protective effects of Min on the heart. Lipopolysaccharide (LPS) was utilized to establish a cardiotoxicity model both in vivo and in vitro. Min was pretreated in the models. In the in vivo setting, evaluation of heart tissue histopathological injury was performed using hematoxylin and eosin (H&E) staining and TUNEL. Immunohistochemistry (IHC) was employed to evaluate the expression levels of NLRP3 and Caspase-1 in the heart tissue of mice. During in vitro experiments, the viability of H9c2 cells was gauged utilizing the CCK8 assay kit. Intracellular ROS levels in H9c2 cells were quantified using a ROS assay kit. Both in vitro and in vivo settings were subjected to measurement of oxidative stress indexes, encompassing glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD) levels. Additionglly, myocardial injury markers like lactate dehydrogenase (LDH) and creatine kinase MB (CK-MB) activity were quantified using appropriate assay kits. Western blotting (WB) analysis was conducted to detect the expression levels of NOD-like receptor protein-3 (NLRP3), caspase-1, IL-18, and IL-1β, alongside apoptosis-related proteins such as Bcl-2 and Bax, and antioxidant proteins including superoxide dismutase-1 (SOD-1) and antioxidant proteins including superoxide dismutase-1 (SOD-2), both in H9c2 cells and mouse heart tissues. In vivo, Min was effective in reducing LPS-induced inflammation in cardiac tissue, preventing cell damage and apoptosis in cardiomyocytes. The levels of LDH and CK-MB were significantly reduced with Min treatment. In vitro studies showed that Min improved the viability of H9C2 cells, reduced apoptosis, and decreased ROS levels in these cells. Further analysis indicated that Min decreased the protein levels of NLRP3, Caspase-1, IL-18, and IL-1β, while increasing the levels of SOD-1 and SOD-2 both in vivo and in vitro. Min alleviates LPS-induced SIC by suppressing the NLRP3/Caspase-1 signalling pathway in vivo and in vitro.

CirSIRT5 induces ferroptosis in bladder cancer by forming a ternary complex with SYVN1/PHGDH

Bladder cancer (BC) represents a prevalent and formidable malignancy necessitating innovative diagnostic and therapeutic strategies. Circular RNAs (circRNAs) have emerged as crucial regulators in cancer biology. In this study, we comprehensively evaluated ferroptosis levels in BC cells utilizing techniques encompassing lipid peroxidation assessment, transmission electron microscopy, and malondialdehyde (MDA) measurement. Additionally, we probed into the mechanistic intricacies by which circRNAs govern BC, employing RNA pull-down, RNA immunoprecipitation (RIP), and immunoprecipitation (IP) assays. Our investigation unveiled circSIRT5, which displayed significant downregulation in BC. Notably, circSIRT5 emerged as a promising prognostic marker, with diminished expression correlating with unfavorable clinical outcomes. Functionally, circSIRT5 was identified as an inhibitor of BC progression both in vitro and in vivo. Mechanistically, circSIRT5 exerted its tumor-suppressive activities through the formation of a ternary complex involving circSIRT5, SYVN1, and PHGDH. This complex enhanced the ubiquitination and subsequent degradation of PHGDH, ultimately promoting ferroptosis in BC cells. This ferroptotic process contributed significantly to the inhibition of tumor growth and metastasis in BC. In addition, FUS was found to accelerate the biogenesis of circSIRT5 in BC. These findings provide valuable insights into the pivotal role of circSIRT5 in BC pathogenesis, underscoring its potential as a diagnostic biomarker and therapeutic target for this malignancy.

Antidepressant potential of β-caryophyllene in maternal separation-induced depression-like in mice: A focus on oxidative stress and nitrite levels

BackgroundMajor depressive disorder is prevalent across different societies, affecting individuals from various cultural and socioeconomic backgrounds. Dysregulation of the nitric oxide (NO) pathway and increased oxidative stress have been implicated as contributing factors. PurposeThis study aimed to explore the antidepressant potential of β-caryophyllene in a mouse model subjected to maternal separation stress, with a focus on its effects on oxidative stress and nitrite levels. Study DesignThe research involved 40 male mice, which were divided into five groups. MethodsThe control group received 1 ml/kg of normal saline, while the maternal separation (MS) groups were administered normal saline in conjunction with β-caryophyllene at doses of 10, 20, and 50 mg/kg. Various behavioral tests, including the open field test (OFT), forced swimming test (FST), and splash test, were employed to assess the impact of β-caryophyllene. Additionally, measurements of total antioxidant capacity (TAC), malondialdehyde (MDA), and nitrite levels in the hippocampus were conducted. ResultsThe findings demonstrated that maternal separation stress induced depressive-like behaviors in mice, as evidenced by increased immobility time in the FST and decreased grooming behavior in the splash test. Furthermore, MS was associated with elevated MDA and nitrite levels and reduced TAC in the hippocampus. However, administration of β-caryophyllene increased grooming activity in the splash test and decreased immobility time in the FST. Additionally, β-caryophyllene exhibited antioxidant properties, lowering MDA and nitrite levels while enhancing TAC in the hippocampus. ConclusionThese results suggest that β-caryophyllene may possess antidepressant-like effects in mice subjected to maternal separation, likely due to its antioxidant actions in the hippocampus.

Canine oocyte nuclear maturation with Nano-ozone (NZS) supplementation: The alterations of antioxidant, and oxidant status and CDK1, cyclin B1 expressions

This study aims to evaluate the effects of nano-ozone solution (NZS) on canine oocyte nuclear maturation, associated with the alterations of antioxidant and oxidant status and cyclin-dependent kinase 1 (CDK1), cyclin B1 gene expressions. Oocytes were cultured in four distinct concentrations of NZS (0.5, 1, 2, and 5 µg/mL) and parthenogenetically activated. The rates of oocytes arrested at the Germinal Vesicle (GV), Germinal Vesicle Breakdown (GVBD), Metaphase I (MI), and Metaphase II (MII) stages were statistically different among groups (P < 0.05). The oocytes cultured in 1 µg/mL NZS yielded the best oocyte maturation rate at the MI and MII stages; however, the lowest maturation and high degeneration rates were observed in Group E. The measurements of Malondialdehyde (MDA), reduced Glutathione (GSH), Superoxide Dismutase (SOD), and Ferric Reducing/Antioxidant Power assay (FRAP) were performed from IVM culture media. No statistical difference was observed in SOD and MDA results (P > 0.05). GSH levels were statistically significant between Group A-Group E (p = 0.003), Group B-Group E (p = 0.045), and Group E-Group D (p = 0.021). The culture media in Group D and Group E had high FRAP concentrations and significantly differed between groups (P < 0.05). CDK1, and cyclin B1 genes, which are subunits of maturation-promoting factor (MPF), are upregulated in Group B and Group C, while are downregulated in oocytes of Group E.This study showed that low, controlled doses of NZS (1 µg/mL) supplementation could improve the meiotic competence of canine oocytes and lead to positive response in expressions of CDK1 and cyclin B1 on the gene level.

Age changes in the gastric mucosa of male albino rat: histological, immunohistochemical, histomorphometric and biochemical study.

Age related changes in the stomach are associated with alterations in the structure and secretory function of the gastric glands. The present study aimed to investigate histological, histomorphometric and biochemical changes in the gastric mucosa of rats with age. Eighty adult male albino rats were randomly divided into four age groups, 20 rats in each (prepubertal, adolescent, adult, and senile). The gastric specimens were subjected to light microscopic examination using haematoxylin and eosin, PAS and Masson's trichrome stains. Immunohistochemical staining for caspase-3 and inducible nitric oxide synthase (iNOS) was carried out. Measurement of superoxide dismutase (SOD), glutathione peroxidase (GPx) and malondialdehyde (MDA) activity in gastric tissue homogenates was performed using ELISA. Quantitative analysis of vascular endothelial growth factor (VEGF) gene expression was done by real-time polymerase chain reaction (PCR). Light microscopic examination of gastric mucosa of senile rats revealed distortion of gastric glands and erosions. Surface mucous cells, mucous neck cells, parietal and chief cells exhibited cytoplasmic destruction, nuclear degeneration, apoptosis and oxidative damage. There was a significant decrease in the mean gastric mucosal thickness, increase in collagen content and decrease in mucous content with the advance of age. These morphological changes were associated with a significant decrease in SOD and GPx activity and increase in MDA activity, in addition to decreased VEGF gene expression. Gastric mucosa of aged rats showed histological and immunohistochemical alterations. These changes were associated with oxidative stress, decreased antioxidant capacity and decreased angiogenesis.

Assessment of ursolic acid effect on in vitro model of cardiac fibrosis

This study aimed to evaluate the effects of ursolic acid (UA) on Angiotensin II (Ang II)-treated neonatal rat cardiac fibroblasts (rCFs) as an in vitro model of cardiac fibrosis. The rCFs were isolated from two-day-old neonatal rats. An in vitro model of cardiac fibrosis was established using 500 nm Ang II treatment for 48 h. The cells were then treated with 5 and 10 μM of UA for 24 and 48 h. Masson's trichrome staining, hydroxyproline content assay, scratch assay, apoptosis assay, measurements of superoxide dismutase (SOD) and malondialdehyde (MDA) levels, real-time PCR, immunocytology and western blotting, were employed to assess the impact of UA. Ang II induced fibrosis in rCFs, as evidenced by the examination of various fibrotic markers. Upon treatment with 5 and 10 μM of UA, the amount of fibrosis in Ang II-treated rCFs was significantly decreased, so that the hydroxyproline concentration was reduced to 0.3 and 0.7 times, respectively. The RNA expression of the Col1a1, Col3a1, Tgfb1, Acta2 and Mmp2 genes had a decrease as well as Nrf2 and HO-1 had an increase after UA treatment. UA could lessen the harmful effects of cardiac fibrosis in a dose- and time-dependent manner, due to its antiapoptotic, antioxidant and cardioprotective properties. This suggests the potential of UA for treatment of cardiac fibrosis.

Celastrol induces ferroptosis by suppressing RRM2 in hepatocellular carcinoma

Introduction and ObjectivesFerroptosis is a novel form of cell death driven by iron dependence and lipid peroxidation, presenting a promising potential as an innovative strategy for cancer treatment. Celastrol (Cel) is particularly effective in inducing ferroptosis, but its molecular mechanism remains unclear. The study aims to elucidate the potential mechanism through both in vitro and in vivo experiments. Materials and methodsCCK-8 assay, Western blot analysis and measurements of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) were performed to investigate how Cel inhibits the proliferation of hepatocellular carcinoma (HCC) cells via the ferroptosis mechanism. Bioinformatics analysis based on the TCGA-LIHC and FerrDb databases was performed to identify the target gene RRM2, and molecular docking-simulated binding between RRM2 and Cel. The role of RRM2 in the effects of Cel was determined through lentiviral transfection, Transwell assays, and in vivo experiments. ResultsCel inhibited HCC cell proliferation via the ferroptosis pathway. Inhibition RRM2 significantly reduces mTOR protein phosphorylation, while overexpressing RRM2 can attenuate theeffects of Cel on the proliferation, migration, invasion, and ferroptosis induction of HCC cells. The result of in vivo experiments in nude mice demonstrated that Cel inhibited tumor growth without adversely affecting liver and kidney function indicators. Immunohistochemistry and Western blot analyses revealed that Cel activated the key proteins in the ferroptosis pathway and affected crucial indicators such as malondialdehyde (MDA) and glutathione (GSH). ConclusionIn this study, we clarifiy the molecular mechanism of Cel, thus broadening its clinical applications for treating various cancer types, including liver cancer.

Investigation of the Effects of N-acetylcysteine and Selenium on Vesicoureteral Reflux Nephropathy: An Experimental Study

IntroductionThis study aimed to investigate the effects of N-acetylcysteine (NAC) and selenium (Se) on vesicoureteral reflux (VUR) nephropathy. MethodsA total of 44 rabbits in 7 groups, namely group 1 (Control), group 2 (VUR + sterile urine), group 3 (VUR + sterile urine + NAC), group 4 (VUR + sterile urine + Se), group 5 (VUR + infected urine), group 6 (VUR + infected urine + NAC) and group 7 (VUR + infected urine + Se), were used. 99mTc Dimercaptosuccinic acid renal scan (DMSA), cystogram and urine culture were performed both at the beginning and end of the study. Left VUR was created surgically, and E. coli was inoculated in infected urine groups. NAC and Se were administered daily for 21 days. Malondialdehyde (MDA) measurement, inflammatory response scores (IRSs), and cicatrization response scores (CRSs) in renal tissues were evaluated. ResultsVUR did not reduce left renal uptake values in neither group 2 nor group 5. MDA levels of the left kidney were significantly higher in group 5 compared to group 1 (p = 0.001). There was no significant difference in MDA levels between group 5 and group 6, and between group 5 and group 7. Left kidney IRSs were found to be higher in all other groups except group 2 compared to the control group (p < 0.001). Left kidney CRSs were significantly higher in group 5 compared to group 2 (p = 0.026), group 6 (p < 0.001) and group 7 (p = 0.006). ConclusionA decrease in renal functions was not observed in VUR, even if there was infection. When CRSs were evaluated, NAC and Se had protective effects in terms of scar formation in VUR nephropathy. Type of StudyExperimental animal study. Levels of EvidenceN/A.

Effect of Andrographis Paniculata Aqueous Extract on Hyperammonemia Induced Alteration of Oxidative and Nitrosative Stress Factors in the Liver, Spleen and Kidney of Rats

ABSTRACT Hyperammonemia (HA) can induce oxidative and nitrosative stress in peripheral organs, potentially exacerbating Hepatic Encephalopathy (HE). This study assessed the efficacy of Andrographis paniculata aqueous extract (APAE) in mitigating oxidative and nitrosative stress caused by non-cirrhotic HA in rat livers, spleens, and kidneys. HA was induced via intraperitoneal injection of ammonium acetate, while APAE was administered orally. The study measured malondialdehyde (MDA), superoxide dismutase (SOD), catalase, and glutathione reductase (GR) to gauge oxidative stress, and nitric oxide (NO) levels as a marker of nitrosative stress. Both acute and chronic HA altered the levels of antioxidant enzymes, MDA, and NO in the organs studied. APAE treatment helped restore SOD, catalase, and GR levels, and decreased MDA and NO levels, demonstrating its potential in reducing oxidative stress linked to HA in the liver, spleen, and kidney.

Effects of Functional Pinealectomy on Immunity, Hematopoietic, Gastrointestinal and Urinary Systems in Experimentally Malnutritioned Rats

Objective: The aim of this study was to demonstrate morphological changes in immunity, hematopoietic, gastrointestinal and urinary systems in different melatonin (MEL) release situations in a rat model of protein energy malnutrition (PEM). Methods: A total of 32 adult male Wistar rats were assigned into four equal groups: normal control; PEM light/dark; PEM light, called functional pinealectomy (Px); and PEM dark. PEM was produced with a 50% restricted diet, Px was produced by keeping rats in continuous light environment for 24 hours, and complete blood count and serum albumin level were analyzed at the end of the 6-week experimental period. Measurements of weights of body and some visceral organs were obtained, biochemical and morphological parameters were analyzed in addition to measurements of malondialdehyde (MDA), total glutatione (GSH), tumor necrosis factor (TNF)-α and interleukin-10 (IL-10) in tissue samples. Results: A reduction in the weights of body and visceral organs of animals in the PEM groups was accompanied by hypoalbuminemia, anemia, leukopenia and lymphopenia, and higher MDA, GSH, TNF-α and IL-10 levels in visceral tissues. There was a significant decrease in parenchymal cells of the liver and spleen, duodenal villi, lymphoid structures and kidney glomeruli, but there was an increase in the spleen capsule thickness and renal Bowman’s space, sinusoidal congestion and fat accumulation in the liver. Importantly, these findings were milder in the PEM dark group, while they were prominent in the PEM light group. Conclusions: This study suggests that MEL has a protective role in reducing the negative effects of PEM, making it a potential therapeutic agent for further investigation.

Alleviating Acute Lung Injury Induced by Lipopolysaccharide: Dayuan Yin Suppresses Inflammation and Oxidative Stress in Elderly Male Rats.

The occurrence of acute lung injury (ALI) caused by lipopolysaccharide (LPS) is prevalent and perilous among older individuals. Inflammation and oxidative stress are vital factors in the progression of ALI in this population. Dayuan Yin (DYY) is a classic Chinese herbal formula used for treating pulmonary diseases. Therefore，this situation can be well simulated by selecting suitable aged rats and induced by LPS, which is helpful to evaluate the role of DYY. The objective of this study is to assess the therapeutic efficacy of DYY in reducing pulmonary inflammation and oxidative stress injury in aged rats induced by LPS. In elderly male Sprague Dawley (SD) rats, the ALI model was induced by injecting LPS into the peritoneal cavity. The therapeutic effect of the DYY group was evaluated after 3 days of oral administration. Lung tissue damage was assessed using hematoxylin-eosin staining and the lung wet/dry (W/D) ratio. Inflammatory reaction in lung tissue was analyzed by counting inflammatory agents, measuring total protein (TP), and examining the concentration of inflammatory components in bronchoalveolar lavage fluid (BALF). Lung oxidative stress was assessed by measuring malondialdehyde (MDA), inducible nitric oxide synthase (iNOS), and superoxide dismutase (SOD) levels in BALF. The impact of DYY on the phosphorylation of PI3K, AKT, and NF-κBp65 protein was analyzed using Western Blot (WB). The administration of DYY exhibited a dose-dependent reduction in the severity of lung injury caused by LPS, leading to a reversal of the LPS-induced lung W/D ratio. Furthermore, DYY treatment resulted in decreased levels of leukocytes, eosinophils, neutrophils, macrophages, lymphocytes, and total protein in BALF. Additionally, DYY significantly inhibited the upregulation of Interleukin -6, Interleukin -10, and Interleukin -1β (IL-6, IL-10, IL-1β) as well as Tumor necrosis factor-α(TNF-α) induced by LPS (P<0.01). The lungs experienced oxidative stress due to LPS, leading to the production of MDA and iNOS, as well as a decrease in SOD activity. DYY reduced oxidative stress in the lungs and inhibited the activation of p-PI3K, p-Akt, and p-NF-κBp65, with a greater effect at higher doses. In a dose-dependent manner, DYY suppresses the inflammatory response and oxidative stress in the lung tissue of elderly rats, thereby reducing ALI caused by LPS. This effect may be attributed to the inhibition of the PI3K/AKT/NF-κB pathway activation.

Sorption Isotherm and Effect of Packaging Materials on Proximate, Organoleptic and Lipid Oxidation Quality of Chicken Nuggets Stored at Two Different Temperatures

The study Investigated sorption isotherm features and the effects of packaging materials of both high-density and low-density polyethylene on sensory properties, proximate composition and lipid oxidation of chicken nuggets in storage. Boneless chicken breast was procured from a reputable source and cut into sizeable weight of 50g each to produce the chicken nuggets used for the studies. The experimental setup for sorption isotherm analysis in this study involved using a gravimetric method to equilibrate the product at various relative humidity levels. Five (5g) grams of oven-dried chicken nugget samples of known moisture content were placed in a controlled humidity chamber, and the weight changes of the samples were monitored until equilibrium was reached. GAB equation was used to evaluate the product ware activity and monolayer moisture. Sensory assessment was evaluated using a 9- point hedonic scale while proximate composition of the chicken nuggets samples was determined according to the methods of the Association of Official Analytical Chemists. Thiobarbituric acid reactive substances (TBARS) assay was used to measure malondialdehyde (MDA) levels as a marker of lipid oxidation. The investigation showed that sensory qualities, proximate composition and lipid oxidation of chicken nuggets were markedly affected by the variance in temperature settings, with distinct disparities seen among different materials for packaging. Chicken nuggets stored at 25 0C caused a significant loss in organoleptic properties and some nutritional composition such as protein and fat. Storage of chicken nugget at 25 0C and 40 C showed a varied values in malondialdehyde as content ranged from 0.52 to 0.81 for chicken nugget stored at 250 C and 0.17 to 0.43 for the product stored at 40 C across the packaging materials investigated. The water activity and monolayer moisture results of sorption analysis revealed that good packaging materials of very low water vapour transmission rate should be used for storage of chicken nuggets as high-density polyethylene offered a promising alternative than low density polyethylene.

Protective Effects of Tunisian Orange Co-Product Extract and Oleuropein-Hesperidin Combination on Bleomycin-Induced Pulmonary Fibrosis in Rats.

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia that leads to acute lung damage, deterioration of lung function, and increased mortality risk. In this study, we investigated the effects of the orange coproduct extract (OCE) and the combination of pure hesperidin and oleuropein (HO) on an experimental model of pulmonary fibrosis induced by bleomycin (BLM) in Wistar rats. Rats were divided into six groups: the control group (G1), the BLM group (G2), three groups (G3, G4, G5) receiving a single dose of BLM combined with OCE extract at 100, 200, and 300 mg/kg, and group 6 (G6) receiving a single dose of BLM combined with HO: both pure major phenolic compounds of OCE (hesperidin at 50 mg/kg) and olive leaves (oleuropein at 2.5 mg/kg). Oxidative stress in lung tissues was investigated using catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX) assays and the measurement of malondialdehyde (MDA) and lactate dehydrogenase (LDH) levels. Treatment with OCE and HO normalized the disturbance in oxidative markers' levels and showed a significant reduction in fibrosis score with no renal or hepatic toxic effects. In conclusion, OCE and HO exhibit antifibrotic effects on a rat model of pulmonary fibrosis.

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

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

Protective Effect of Resveratrol Combined with Levodopa Against Oxidative Damage in Dopaminergic Neurons.

Levodopa (L-3,4-dihydroxyphenylalanine, L-Dopa) alleviates the symptoms of Parkinson's disease (PD), yet prolonged usage may give rise to severe adverse effects. Resveratrol (RSV) is a potent antioxidant, anticancer and anti-inflammatory agent. And a variety of polyphenol antioxidant compounds derived from RSV combined with levodopa have demonstrated neuroprotective activity against neuronal cell death. The purpose of this study was to examine the impact of this combination of RSV and L-Dopa on the survival rate, growth status, and reactive oxygen species (ROS) of MES23.5 dopamine (DA) neuron cells. In this study, we induced MPP+ in MES23.5 dopamine neuron cells and observed their survival rate, growth status, ROS content, as well as the effect of RSV combined with L-Dopa on cell survival. We also measured malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity levels as indicators of mitochondrial function, oxidative stress, and oxidative damage in the cells. Our results indicated that the MES23.5 dopamine neurons had decreased survival, poor growth status, and increased ROS content after MPP+ induction. Moreover, we found that MDA levels were elevated, and SOD activity levels were decreased, suggesting that the cells experienced abnormal mitochondrial function. However, when RSV was combined with L-Dopa, the cells showed a reduced level of MPP + -induced oxidative damage, with a more significant inhibitory effect observed in the RSV group at a concentration of 50 μmol/L. In conclusion, we found that the effects of co-administration of RSV with L-Dopa (100 μmol/L) was more effective than L-Dopa administered at the high dose. Thus, we found that RSV has the potential to reduce the dose of L-Dopa required to improve PD symptoms.

Xinyang tablet alleviated cardiac dysfunction in a cardiac pressure overload model by regulating the receptor-interacting serum/three-protein kinase 3/FUN14 domain containing 1-mediated mitochondrial unfolded protein response and mitophagy

Ethnopharmacological relevanceXinyang tablet (XYT) has been used for heart failure (HF) for over twenty years in clinical practice, but the underlying molecular mechanism remains poorly understood. Aims of the studyIn the present study, we aimed to explore the protective effects of XYT in HF in vivo and in vitro. Materials and methodsTransverse aortic constriction was performed in vivo to establish a mouse model of cardiac pressure overload. Echocardiography, tissue staining, and real-time quantitative PCR (qPCR) were examined to evaluate the protective effects of XYT on cardiac function and structure. Adenosine 5′-triphosphate production, reactive oxygen species staining, and measurement of malondialdehyde and superoxide dismutase was used to detect mitochondrial damage. Mitochondrial ultrastructure was observed by transmission electron microscope. Immunofluorescence staining, qPCR, and Western blotting were performed to evaluate the effect of XYT on the mitochondrial unfolded protein response and mitophagy, and to identify its potential pharmacological mechanism. In vitro, HL-1 cells and neonatal mouse cardiomyocytes were stimulated with Angiotensin II to establish the cell model. Western blotting, qPCR, immunofluorescence staining, and flow cytometry were utilized to determine the effects of XYT on cardiomyocytes. HL-1 cells overexpressing receptor-interacting serum/three-protein kinase 3 (RIPK3) were generated by transfection of RIPK3-overexpressing lentiviral vectors. Cells were then co-treated with XYT to determine the molecular mechanisms. ResultsIn the present study, XYT was found to exerta protective effect on cardiac function and structure in the pressure overload mice. And it was also found XYT reduced mitochondrial damage by enhancing mitochondrial unfolded protein response and restoring mitophagy. Further studies showed that XYT achieved its cardioprotective role through regulating the RIPK3/FUN14 domain containing 1 (FUNDC1) signaling. Moreover, the overexpression of RIPK3 successfully reversed the XYT-induced protective effects and significantly attenuated the positive effects on the mitochondrial unfolded protein response and mitophagy. ConclusionsOur findings indicated that XYT prevented pressure overload-induced HF through regulating the RIPK3/FUNDC1-mediated mitochondrial unfolded protein response and mitophagy. The information gained from this study provides a potential strategy for attenuating mitochondrial damage in the context of pressure overload-induced heart failure using XYT.

Evaluation of In Vitro and In Vivo Antioxidant Potential of the Ethyl Acetate Fraction of Cyperus Pangorei Rhizome

Background and Aim: Antioxidants derived from natural sources, particularly those rich in flavonoids and phenolic compounds, have attracted considerable interest for their potential health benefits in combating oxidative stress-related diseases. This study aimed to evaluate the antioxidant potential of the ethyl acetate (EtAc) fraction obtained from Cyperus pangorei rhizome, focusing on both in vitro and in vivo assessments. Methods: The EtAc fraction was subjected to RP-HPLC analysis to identify and quantify phenolic compounds and flavonoids. Acute toxicity testing was performed to assess the safety profile of the EtAc fraction. In vitro antioxidant activity was determined using DPPH and ABTS+ radical scavenging assays. In vivo evaluation of antioxidant activity was conducted in Triton X-100-induced oxidative stress model in mice, measuring malondialdehyde (MDA) content, glutathione (GSH) levels, and superoxide dismutase (SOD) activity in liver tissues. Results: RP-HPLC analysis confirmed the presence of quercetin, luteolin, and apigenin in the EtAc fraction. The fraction exhibited significant dose-dependent antioxidant activity in both DPPH and ABTS+ assays, with IC50 values indicating potent scavenging effects. In the Triton X-100-induced stress model, administration of the EtAc fraction led to a reduction in MDA levels, restoration of GSH levels, and enhancement of SOD activity in mouse liver tissues. Conclusion: The findings suggest that the EtAc fraction from C. pangorei possesses promising antioxidant properties, as evidenced by its ability to mitigate oxidative stress-related damage both in vitro and in vivo.

Antioxidant production promotes defense mechanism and different gene expression level in Zeamays under abiotic stress

The growth and productivity of maize are severely affected by soil salinity. The crucial determinants for the future performance of plants are productive for seed germination and seedling establishment; however, both stages are liable to soil salinity. For grain, maize is an economically significant crop sensitive to abiotic stresses. However, little is known about defense responses by the salinity-induced antioxidant and oxidative stress in maize. In our work, the commercially available maize variety Raka-Poshi was grown in pots for 30 days under greenhouse conditions. To evaluate the salt-induced oxidative/antioxidant responses in maize for salt stress 0, 25, 50, 75, 100 and 150 mM concentrations, treatments were provided using sodium chloride (NaCl). All the biochemical indices were calculated under all NaCl concentrations, while drought was induced by up to 50% irrigation water. After 30 days of seed germination, the maize leaves were collected for the measurement of lipid peroxidase or malondialdehyde (MDA), glutathione reductase (GR), guaiacol peroxidase (GPOD), hydrogen peroxide (H2O2), superoxide dismutase (SOD), lipoxygenase (LOX), catalase (CAT), ascorbate peroxidase (APOD) and glutathione-S-transferase (GST). The results revealed a 47% reduction under 150 mM NaCl and 50% drought stress conditions. The results have shown that the successive increase of NaCl concentrations and drought caused an increase in catalase production. With successive increase in NaCl concentration and drought stress, lower levels of H2O2, SOD, and MDA were detected in maize leaves. The results regarding the morphology of maize seedlings indicated a successive reduction in the root length and shoot length under applications of salt and drought stress, while root-to-shoot weights were found to be increased under drought stress and decreased under salt stress conditions During gene expression analysis collectively indicate that, under drought stress conditions, the expression levels of all nine mentioned enzyme-related genes were consistently downregulated.

Quercetin promotes ATG5-mediating autophagy-dependent ferroptosis in gastric cancer.

Quercetin has been documented to possess a multitude of pharmacological effects, encompassing antioxidant, antiviral, antimicrobial, and anti-inflammatory properties. Nevertheless, the exact molecular mechanisms responsible for the anti-tumor properties of quercetin remain to be fully explicated. To this end, quercetin was administered to gastric cancer cells (in vitro) AGS and MKN45, as well as BALB/c mice (in vivo). The proliferation ability of cells was evaluated using cholecystokinin octapeptide (CCK-8) and colony formation assays. The evaluation of ferroptosis involved the measurement of iron, malondialdehyde (MDA), and lipid reactive oxygen species. Autophagy and apoptosis were evaluated using immunofluorescence staining, western blotting, and flow cytometry analysis. Our findings indicate that quercetin significantly inhibited cell viability and tumor volume compared to the control group. Additionally, quercetin was found to decrease glutathione (GSH), malondialdehyde, and reactive oxygen species (ROS) levels while suppressing beclin1 and LC3B levels in cancer cells. Remarkably, the utilization of siATG5 was found to reverse all the aforementioned effects of quercetin. Ultimately, the effects of quercetin on gastric cancer were validated. In summary, our findings provide evidence that quercetin facilitates autophagy-mediated ferroptosis in gastric cancer.

Ovarian ferroptosis induced by androgen is involved in pathogenesis of PCOS.

Does ovarian ferroptosis play an active role in the development of polycystic ovary syndrome (PCOS)? Increased ovarian ferroptosis was present in PCOS ovaries and the inhibition of ferroptosis with ferrostatin-1 (Fer-1) ameliorated polycystic ovary morphology and anovulation. Programmed cell death plays a fundamental role in ovarian follicle development. However, the types and mechanisms of cell death involved in the ovary are yet to be elucidated. Ferroptosis is a recently discovered iron-dependent programmed cell death. Impaired iron metabolism and cell death have been observed in women with PCOS, the main cause of anovulatory infertility. Additionally, previous studies reported that an abnormal expression of noncoding RNA may promote ferroptosis in immortalized ovarian granulosa cell lines. However, little is known about whether ovarian ferroptosis is increased in PCOS, and there is insufficient direct evidence for a role of ferroptosis in PCOS, and the underlying mechanism. Moreover, the effect of the inhibition of ferroptosis with Fer-1 in PCOS remains unclear. Ferroptosis was evaluated in human granulosa cells (hGCs) from non-PCOS (n = 6-16) and PCOS (n = 7-18) patients. The experimental study was completed in vitro using primary hGCs from women undergoing IVF. Improvements in PCOS indicators following ferroptosis inhibition with Fer-1 were investigated in a dehydroepiandrosterone (DHEA)-induced PCOS rat model (n = 8 per group). Ovarian ferroptosis was evaluated in the following ways: by detecting iron concentrations via ELISA and fluorescent probes; measuring malondialdehyde (MDA) concentrations via ELISA; assessing ferroptosis-related protein abundance with western blotting; observing mitochondrial morphology with transmission electron microscopy; and determining cell viability. Primary hGCs were collected from women undergoing IVF. They were treated with dihydrotestosterone (DHT) for 24 h. The effect of DHT on ferroptosis was examined in the presence or absence of small interfering RNA-mediated knockdown of the putative receptor coregulator for signaling molecules. The role of ovarian ferroptosis in PCOS progression was explored in vivo in rats. The DHEA-induced PCOS rat model was treated with the ferroptosis inhibitor, Fer-1, and the oocytes and metaphase II oocytes were counted after ovarian stimulation. Additionally, rats were treated with the ferroptosis inducer, RSL3, to further explore the effect of ferroptosis. The concentrations of testosterone, FSH, and LH were assessed. Increased ferroptosis was detected in the ovaries of patients with PCOS and in rats with DHEA-induced PCOS. Increased concentrations of Fe2+ (P < 0.05) and MDA (P < 0.05), and upregulated nuclear receptor coactivator 4 protein levels, and downregulated ferritin heavy chain 1 (FTH1) and glutathione peroxidase 4 (GPX4) proteins were observed in the hGCs in patients with PCOS and ovaries of PCOS rats (P < 0.05 versus control). DHT was shown to induce ferroptosis via activation of NOCA4-dependent ferritinophagy. The inhibition of ferroptosis with Fer-1 in rats ameliorated a cluster of PCOS traits including impaired glucose tolerance, irregular estrous cycles, reproductive hormone dysfunction, hyperandrogenism, polycystic ovaries, anovulation, and oocyte quality (P < 0.05). Treating rats with RSL3 resulted in polycystic ovaries and hyperandrogenism (P < 0.05). N/A. Although ovarian-targeted ferroptosis inhibition may be a more targeted treatment for PCOS, the underlying mechanisms in the cycle between ferroptosis and hyperandrogenism require further exploration. Additionally, since PCOS shows high heterogeneity, it is important to investigate whether ferroptosis increases are present in all patients with PCOS. Androgen-induced ovarian ferroptosis appears to play a role in the pathogenesis of PCOS, which potentially makes it a promising treatment target in PCOS. This study was supported by the National Key R&D Program of China (2023YFC2705500, 2023YFC2705505, 2019YFA0802604), National Natural Science Foundation of China (No. 82130046, 82320108009, 82101708, 82101747, and 82001517), Shanghai leading talent program, Innovative research team of high-level local universities in Shanghai (No. SHSMU-ZLCX20210201, No. SSMU-ZLCX20180401), Shanghai Jiaotong University School of Medicine, Affiliated Renji Hospital Clinical Research Innovation Cultivation Fund Program (RJPY-DZX-003) and Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (No. 20161413), Shanghai's Top Priority Research Center Construction Project (2023ZZ02002), and Three-Year Action Plan for Strengthening the Construction of the Public Health System in Shanghai (GWVI-11.1-36). The authors report no competing interests.