Oxidative Stress-induced Cell Injury Research Articles

Exploring the Cardiovascular Protective Effects of Baicalin: A Pathway to New Therapeutic Insights.

Cardiovascular disorders develop the highest rates of mortality and morbidity worldwide, emphasizing the need for novel pharmacotherapies. The Chinese medicinal plant S. baicalensis has a number of major active components, one of which is called baicalin. According to emerging research, baicalin reduces chronic inflammation, immunological imbalance, lipid metabolism, apoptosis, and oxidative stress. Baicalin improves endothelial function and protects the cardiovascular system from oxidative stress-induced cell injury by scavenging free radicals and inhibiting xanthine oxidase. Therefore, it helps prevent CVD such as hypertension, atherosclerosis, and cardiac arrest. In this review, the therapeutic effects of baicalein are discussed in relation to both the prevention and management of cardiovascular diseases.

Assessment of Add-On Therapy of N-Acetylcysteine in the Management of Acute Pancreatitis

Abstract Background Acute pancreatitis (AP) is an inflammation of the pancreas. The conservative therapeutic options include enteral nutrition, antibiotics, and/or surgery. Oxidative stress in AP has been pathologically linked with the systemic inflammatory response. N-acetylcysteine (NAC), an antioxidant, attenuates oxidative stress-induced cell injury and other potential pathological events in AP. Objective This article evaluates the treatment outcome of NAC combined with conventional therapy in AP patients and assesses the difference in the duration of hospital stay between the NAC with conventional therapy group and the conventional therapy group. Materials and Methods This observational study was conducted in a tertiary care hospital with 65 AP patients above 18 years of age. The effect of adding NAC with conventional therapy (intravenous hydration 0.9% normal saline, pancreatin, optional antibiotics) was assessed in patients by comparing serum amylase, lipase, Acute Physiology and Chronic Health Examination (APACHE) II score, and Ranson's score, before and after therapy and the difference in duration of hospital stay was assessed using the independent t-test. Results Of the 65 AP patients, 62% (n = 40) were on conventional therapy and 38% (n = 25) were on NAC along with conventional therapy. The difference in mean values of reduced serum amylase between the two treatment groups indicates a significant difference (p = 0.01). However, the variance in mean serum lipase values was statistically insignificant (p = 0.1). The mean scores of Ranson's criteria showed no significant difference between both groups (p = 0.4). There was a significant difference in APACHE II severity scores after 24 (p = 0.04) and 48 hours (p = 0.01), respectively. Similarly, the mean duration of hospital stay in both treatment groups was found to be statistically insignificant (p = 0.4). Conclusion Both treatment options, conventional therapy and NAC combined with conventional therapy, resulted similar treatment outcomes for AP patients, with no additional benefits observed.

LncRNA-SNHG16 Protects Against Oxidative Stress-Induced Vascular Endothelial Cell Injury in Cardiovascular Diseases by Regulating the miR-23a-3p-GLS-Glutamine Metabolism Axis.

Cardiovascular diseases are disorders of the heart and vascular system that cause high mortality rates worldwide. Vascular endothelial cell (VEC) injury caused by oxidative stress (OS) is an important event in the development of various cardiovascular diseases, including ischemic heart disease. This study aimed to investigate the critical roles and molecular mechanisms of long non-coding RNA (lncRNA) SNHG16 in regulating vascular endothelial cell injury under oxidative stress. We demonstrated that SNHG16 was significantly downregulated and miRNA-23a-3p was notably induced in human vascular endothelial cells under OS. Overexpressing SNHG16 or silencing miR-23a-3p effectively mitigated the OS-induced VEC injury. Additionally, glutamine metabolism of VECs was suppressed under OS. SNHG16 protected the OS-suppressed glutamine metabolism, while miR-23a-3p functioned oppositely in VECs. Furthermore, SNHG16 downregulated miR-23a-3p by sponging miR-23a-3p, which direct targeted the glutamine metabolism enzyme, GLS. Finally, restoring miR-23a-3p in SNHG16-overexpressing VECs successfully reversed the protective effect of SNHG16 on vascular endothelial cell injury under OS. In summary, our results revealed the roles and molecular mechanisms of the SNHG16-mediated protection against VEC injury under OS by modulating the miR-23a-3p-GLS pathway.

Preparation and Evaluation of Curcumin Derivatives Nanoemulsion Based on Turmeric Extract and Its Antidepressant Effect.

The early stage of this study verified that a turmeric extract (TUR) including 59% curcumin (CU), 22% demethoxycurcumin (DMC), and 18% bisdemethoxycurcumin (BDMC), could enhance the stability of CU and had greater antidepressant potential in vitro. The objective of the study was to develop a nano-delivery system containing TUR (TUR-NE) to improve the pharmacokinetic behavior of TUR and enhance its antidepressant effect. The antidepressant potential of TUR was explored using ABTS, oxidative stress-induced cell injury, and a high-throughput screening model. TUR-NE was fabricated, optimized and characterized. The pharmacokinetic behaviors of TUR-NE were evaluated following oral administration to normal rats. The antidepressant effect of TUR-NE was assessed within chronic unpredictable mild stress model (CUMS) mice. The behavioral and biochemical indexes of mice were conducted. The results depicted that TUR had 3.18 and 1.62 times higher antioxidant capacity than ascorbic acid and CU, respectively. The inhibition effect of TUR on ASP+ transport was significantly enhanced compared with fluoxetine and CU. TUR-NE displayed a particle size of 116.0 ± 0.31 nm, polydispersity index value of 0.121 ± 0.007, an encapsulation rate of 98.45%, and good release and stability in cold storage. The results of pharmacokinetics indicated the AUC(0-t) of TUR-NE was 8.436 and 4.495 times higher than that of CU and TUR, while the Cmax was 9.012 and 5.452 times higher than that of CU and TUR, respectively. The pharmacodynamic study confirmed that the superior antidepressant effect of TUR-NE by significantly improving the depressant-like behaviors and elevating the content of 5-hydroxytryptamine in plasma and brain in CUMS mice. TUR-NE showed good safety with repeated administration. TUR-NE, which had small and uniform particle size, enhanced the bioavailability and antidepressant effect of TUR. It could be a promising novel oral preparation against depression.

Lycopene alleviates oxidative stress-induced cell injury in human vascular endothelial cells by encouraging the SIRT1/Nrf2/HO-1 pathway

ABSTRACT Background and objective: Epidemiological research have displayed that dietary intake rich in lycopene, an antioxidant, is negatively correlated with the risk of cardiovascular disease (CVD). This study aimed to investigate whether the intervention with different concentrations of lycopene could attenuate H2O2-induced oxidative stress injury in human vascular endothelial cells (VECs). Methods: The human VECs HMEC-1 and ECV-304 were incubated with a final concentration of 300 µmol/L H2O2, followed by they were incubated with lycopene at doses of 0.5, 1, or 2 µm. Subsequently, cell proliferation, cytotoxicity, cell adhesion, reactive oxygen species (ROS) contents, adhesion molecule expression, oxidative stress levels, pro-inflammatory factor production, the apoptosis protein levels, and the silent information regulator-1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway protein levels were tested by CCK-8 kit, lactate dehydrogenase (LDH) kit, immunofluorescence labeling, cell surface enzyme immunoassays (EIA), enzyme-linked immunosorbent assay (ELISA), as well as Western blot assays, respectively. Results: Under H2O2 stimulation, HMEC-1 and ECV-304 cell proliferation and the SIRT1/Nrf2/HO-1 pathway protein expression were significantly reduced, whereas cytotoxicity, apoptosis, cell adhesion molecule expression, pro-inflammatory and oxidative stress factors production were apparently encouraged, which were partially countered by lycopene intervention in a dose-dependent manner. Conclusion: Lycopene alleviates H2O2-induced oxidative damage in human VECs by reducing intracellular ROS levels, inflammatory factor production, cell adhesiveness, and apoptosis rate under oxidative stress conditions through activation of the SIRT1/Nrf2/HO-1 pathway.

Downregulation of miR-192 Alleviates Oxidative Stress-Induced Porcine Granulosa Cell Injury by Directly Targeting Acvr2a.

Follicular atresia is primarily caused by breakdown to granulosa cells (GCs) due to oxidative stress (OS). MicroRNAs (miRNAs) elicit a defense response against environmental stresses, such as OS, by acting as gene-expression regulators. However, the association between miRNA expression and OS in porcine GCs (PGCs) is unclear. Here, we examined the impact of H2O2-mediated OS in PGCs through miRNA-Seq. We identified 22 (14 upregulated and 8 downregulated) and 33 (19 upregulated and 14 downregulated) differentially expressed miRNAs (DEmiRNAs) at 100 μM and 300 μM H2O2, respectively, compared with the control group. Among the DEmiRNAs, mi-192 was most induced by H2O2-mediated OS, and the downregulation of miR-192 alleviated PGC oxidative injury. The dual-luciferase reporter assay results revealed that miR-192 directly targeted Acvr2a. The Acvr2a level was found to be remarkably decreased after OS. Furthermore, grape seed procyanidin B2 (GSPB2) treatment significantly reduced the H2O2-induced upregulation of miR-192, and decreased PGC apoptosis and oxidative damage. Meanwhile, GSPB2 prevented an H2O2-induced increase in caspase-3 activity, which was enhanced by the application of the miR-192 inhibitor. These results indicate that GSPB2 protects against PGC oxidative injury via the downregulation of miR-192, the upregulation of Acvr2a expression, and the suppression of the caspase-3 apoptotic signaling pathway.

Puerarin protects against H2O2-induced apoptosis of HTR-8/SVneo cells by regulating the miR-20a-5p/VEGFA/Akt axis

IntroductionPreeclampsia seriously affects the health of pregnant women and fetuses. It has been reported that puerarin has a positive therapeutic effect on the treatment of preeclampsia. In this study, oxidative stress-induced trophoblast cell injury was established to explore the potential interaction between puerarin and preeclampsia. MethodsA CCK-8 assay was performed to investigate the effect of puerarin on the viability of HTR-8/SVneo cells. To mimic oxidative stress-induced trophoblast cell injury, human villous trophoblasts (HTR-8/SVneo) were treated with H2O2. Then, the relationships among MMP2, VEGFA and miR-20a-5p in HTR-8/SVneo cells were confirmed using a dual-luciferase reporter assay. Finally, Western blot assays were performed to measure the expression levels of MMP2, VEGFA, p-Akt, Akt, Bcl-2 and cleaved caspase 3. ResultsIn this study, puerarin eliminated H2O2-induced cytotoxicity of HTR-8/SVneo cells. In addition, puerarin was able to reverse H2O2-induced apoptosis and metastasis inhibition in cells. Meanwhile, puerarin significantly abrogated H2O2-induced mitochondrial membrane potential (MMP) decline in HTR-8/SVneo cells. And, MMP2 and VEGFA were identified as direct targets of miR-20a-5p. Furthermore, puerarin reversed H2O2-induced growth inhibition in HTR-8/SVneo cells by regulating the miR-20a-5p/VEGFA/Akt axis. DiscussionAll these data indicated that puerarin could abolish H2O2-induced growth inhibition in HTR-8/SVneo cells by regulating the miR-20a-5p/VEGFA/AKT axis.

The Use of Quercetin to Improve the Antioxidant and Regenerative Properties of Frozen or Cryopreserved Human Amniotic Membrane.

The biological properties of the human amniotic membrane (HAM) and its characteristic ability to be a reservoir of growth factors promoting wound healing make it an ideal biological dressing for the treatment of different clinical conditions, such as burns and non-healing wounds. However, the application of a preservation method on the HAM is required during banking to maintain biological tissue properties and to ensure the release overtime of protein content for its final clinical effectiveness after application on the wound bed. Although cryopreservation and freezing are methods widely used to maintain tissue properties, reactive oxygen species (ROS) are produced within tissue cellular components during their switching from frozen to thawed state. Consequently, these methods can lead to oxidative stress-induced cell injury, affecting tissue regenerative properties and its final clinical effectiveness. Taking advantage of the antioxidant activity of the natural compound quercetin, we used it to improve the antioxidant and regenerative properties of frozen or cryopreserved HAM tissues. In particular, we evaluated the oxidative damage (lipid peroxidation, malondialdehyde) as well as the regenerative/biological properties (bFGF growth factor release, wound healing closure, structure, and viability) of HAM tissue after its application. We identified the effectiveness of quercetin on both preservation methods to reduce oxidative damage, as well as its ability to enhance regenerative properties, while maintaining the unaltered structure and viability of HAM tissue. The use of quercetin described in this study appears able to counteract the side effects of cryopreservation and freezing methods related to oxidative stress, enhancing the regenerative properties of HAM. However, further investigations will need to be performed, starting from these promising results, to identify its beneficial effect when applied on burns or non-healing wounds.

Ginsenoside Rb1 inhibits oxidative stress-induced ovarian granulosa cell injury through Akt-FoxO1 interaction

Ginsenoside Rb1 shows a strong antioxidant effect and has potential activation effects on Akt. The aim of the present study was to investigate the protective effect of Rb1 on age-related ovarian granulosa cell injury. Ovarian granulosa cells (GCs) were obtained from 50 young women (≤30 years) and 50 aged women (≥38 years) at an IVF center. Young and aged ICR mice were administered with or without Rb1 (10 mg kg-1, i.p.) for 2 weeks. The protective effects of Rb1 were investigated and the role of Rb1 on the modulation of Akt-FoxO1 interaction was determined with immunofluorescence, Western blotting, immunoprecipitation, siRNA silencing and pharmacological inhibitor. Rb1 effectively decreased LDH and MDA, and reversed the apoptotic-related protein levels in hGL cells from old patients. Similar results were found in mice. In addition, the mitochondrial membrane potential was restored and the overaccumulation of ROS was reversed by Rb1. Rb1 preserved peroxide-impaired Akt activation, to some extent, by increasing phosphorylation at Ser473. Rb1 also facilitated p-Akt binding to FoxO1 and promoted the phosphorylation of FoxO1. SiRNA silencing of Akt, Akt inhibitor LY294002, and FoxO1 inhibitor AS1842856 attenuated the effects of Rb1. Ginsenoside Rb1 inhibits age-related GCs oxidative damage by activating Akt phosphorylation at Ser473 and by further interaction with FoxO1.

Uterine prolactin and IGFBP1 in the offspring of diabetic rats: Effects of a maternal diet enriched in olive oil

Preeclampsia seriously affects the health of pregnant women and fetuses. It has been reported that puerarin has a positive therapeutic effect on the treatment of preeclampsia. In this study, oxidative stress-induced trophoblast cell injury was established to explore the potential interaction between puerarin and preeclampsia.A CCK-8 assay was performed to investigate the effect of puerarin on the viability of HTR-8/SVneo cells. To mimic oxidative stress-induced trophoblast cell injury, human villous trophoblasts (HTR-8/SVneo) were treated with H2O2. Then, the relationships among MMP2, VEGFA and miR-20a-5p in HTR-8/SVneo cells were confirmed using a dual-luciferase reporter assay. Finally, Western blot assays were performed to measure the expression levels of MMP2, VEGFA, p-Akt, Akt, Bcl-2 and cleaved caspase 3.In this study, puerarin eliminated H2O2-induced cytotoxicity of HTR-8/SVneo cells. In addition, puerarin was able to reverse H2O2-induced apoptosis and metastasis inhibition in cells. Meanwhile, puerarin significantly abrogated H2O2-induced mitochondrial membrane potential (MMP) decline in HTR-8/SVneo cells. And, MMP2 and VEGFA were identified as direct targets of miR-20a-5p. Furthermore, puerarin reversed H2O2-induced growth inhibition in HTR-8/SVneo cells by regulating the miR-20a-5p/VEGFA/Akt axis.All these data indicated that puerarin could abolish H2O2-induced growth inhibition in HTR-8/SVneo cells by regulating the miR-20a-5p/VEGFA/AKT axis.

The heart as a target for deltamethrin toxicity: Inhibition of Nrf2/HO-1 pathway induces oxidative stress and results in inflammation and apoptosis

As a synthetic pyrethroid pesticide, deltamethrin (DLM) is widely employed in veterinary medicine and farming, and DLM-triggered oxidative stress largely causes serious harm to the organism. It is well-known that nuclear factor erythroid-2-related factor 2/heme oxygenase-1 (Nrf2/HO-1), a pivotal endogenous anti-oxidative pathway, acts on inhibiting oxidative stress-induced cell injury under the activated state. The purpose of this research was to observe the impact and molecular mechanism of DLM on inflammation and apoptosis in quail cardiomyocytes based on the Nrf2/HO-1 signaling route. In this research, quails were established as a cardiac injury model through gastric infusion of various doses of DLM (0, 15, 30, and 45 mg/kg b. w.) for 12 weeks. Our results showed that DLM could induced cardiomyocyte injury in a dose-dependent manner though weakening antioxidant defense via down-regulating Nrf2 and its downstream protein HO-1. Furthermore, DLM stimulation induced apoptosis in quail heart by decreasing the protein expressions of B-cell lymphoma-extra large and B-cell lymphoma gene 2 (Bcl-2), as well as increasing P53, caspase 3, and Bcl-2-associated X protein levels. Meanwhile, relative levels of nuclear factor-kappa B and interleukin-1β in quail hearts were up-regulated under DLM intervention progressively. Collectively, our study demonstrates that chronic exposure to DLM can induce quail cardiomyocyte inflammation and apoptosis by mediating Nrf2/HO-1 signaling pathway-related oxidative stress.

WD-40 repeat protein 26 protects against oxidative stress-induced injury in astrocytes via Nrf2/HO-1 pathways.

Stroke is the leading cause of disability and the third leading cause of death in the world, and no effective treatment has been developed. Oxidative stress-induced cell injury and genomic instability is implicated in the pathogenesis of stroke, whose prognosis remains poor. A model of cerebral ischemic/reperfusion injury model was established through four artery occlusions. This study was carried out using western blot, flow cytometry and RT-PCR on cell line U251-MG. The cytotoxic effect of H2O2 and expression of LDH, caspase-3, MDA and SOD was analyzed by assay kit. We found that the expression of WDR26 was induced in cerebral ischemia-reperfusion injury in vivo and the expression of WDR26 was induced by H2O2 in a dose- and time-dependent manner in vitro. WDR26 over-expression significantly suppressed H2O2-induced cell death and caspase-3-mediated apoptosis in U251-MG cells. In contrast, inhibition of WDR26 markedly enhanced cell death in U251-MG cells. In addition, WDR26 regulated oxidative stress response and induced Nrf2/HO-1 pathway. These findings suggest that WDR26 mediates H2O2-induced oxidative stress and cell injury, possibly by reducing the intrinsic apoptotic pathway and activating Nrf2 and HO-1 in astrocytes.

Induction of Sirtuin1 Activity in SH-SY5Y Cells by Cyanidin-3-O-Glucocide Induced

An increase in oxidative stress plays a key role in neurotoxicity induction and cell death, which leads to neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. Cyanidin-3-glucoside (C3G) is a common anthocyanin and shows antioxidant activity in neuronal cells. Silent information regulator 2-related protein 1 (Sirt1) regulates antioxidant and anti-inflammatory effects. However, the effects of C3G on Sirt1 in neuronal cells remain unclear. This study evaluated the effect of C3G on Sirt1 expression and activity in human neuroblastoma (SH-SY5Y) cells. In the study, C3G increased the expression of Sirt1 and Sirt1 activity in SH-SY5Y cells. Additionally, C3G increased the expression of nuclear factor erythroid 2-related factor 2, a vital transcription factor for regulating the expression of antioxidant genes, as well as antioxidant enzymes such as superoxide dismutase and catalase. Moreover, C3G protected SH-SY5Y cells from oxidative stress. These results suggest that C3G decreased oxidative stress-induced cell injury by increasing the expression of Sirt1 and other antioxidant factors. Therefore, C3G might merit further investigation for use in attenuating the progress of neurodegenerative diseases.

The regulatory role of MiR-203 in oxidative stress induced cell injury through the CBS/H2S pathway

Hydrogen Sulfide (H2S) mediates biological effects in a variety of ways. Due to its strong reducing potential, H2S has been recognized to have an important role in oxidative stress induced hypoxia. It has been reported that H2S production and miRNA can mutually regulate each other. H2S is produced by the catalytic activity of cystathionine-β-synthase (CBS), which is under the regulation of miRNAs. In this study, we used target gene prediction software, and identified miR-203 as a potential regulator of CBS. We verified this finding using an oxygen and glucose deprivation (OGD) hypoxia cell model in SH-SY5Y cells and pMIR-REPORT™ luciferase miRNA expression reporter vector. Furthermore, transfecting SH-SY5Y cells with miRNA agomir (agonist) and antagomir (antagonist) by lipofectamin RNAiMAX, we further validated miR-203 as a direct regulator of CBS. We also found that miR-203 protects from cell injury by regulating lipid peroxidation, cell apoptosis, and mitochondrial membrane potential. These findings suggest that while over-expression of miR-203 can aggravate OGD induced cell injury, inhibition of miR-203 can protect against OGD induced cell injury. Based on our data and that of others, we propose that miR-203 may regulate oxidative stress induced cell injury by regulating CBS expression and adjusting the levels of H2S production.

Alpha-lipoic acid protects human dopaminergic neuronal cells against hydrogen peroxide-induced cell injury by inhibiting autophagy and apoptosis

Alpha-lipoic acid (ALA) is a naturally occurring antioxidant and has been previously used to treat diabetes and cardiovascular disease. However, the autophagy effects of ALA against oxidative stress-induced dopaminergic neuronal cell injury remain unclear. The aim of this study was to investigate the role of ALA in autophagy and apoptosis against oxidative stress in the SH-SY5Y human dopaminergic neuronal cell line. We examined SH-SY5Y phenotypes using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay (cell viability/proliferation), 4′,6-diamidino-2-phenylindole dihydrochloride nuclear staining, Live/Dead cell assay, cellular reactive oxygen species (ROS) assay, immunoblotting, and immunocytochemistry. Our data showed ALA attenuated hydrogen peroxide (H2O2)-induced ROS generation and cell death. ALA effectively suppressed Bax up-regulation and Bcl-2 and BclxL down-regulation. Furthermore, ALA increased the expression of the antioxidant enzyme, heme oxygenase-1. Moreover, the expression of Beclin-1 and LC-3 autophagy biomarkers was decreased by ALA in our cell model. Combined, these data suggest ALA protects human dopaminergic neuronal cells against H2O2-induced cell injury by inhibiting autophagy and apoptosis.

CircRNA expression profile and functional analysis in retinal ischemia-reperfusion injury

Retinal ischemia-reperfusion (I/R) is involved in the pathogenesis of many vision-threatening diseases. circRNAs act as key players in gene regulation and human diseases. However, the global circRNA expression profile in retinal I/R injury has not been fully uncovered. Herein, we established a murine model of retinal I/R injury and performed circRNA microarrays to identify I/R-related circRNAs. 1265 differentially expressed circRNAs were identified between I/R retinas and normal retinas. Notably, the detection of cWDR37 level in aqueous humor could discriminate glaucoma patients from cataract patients (AUC = 0.9367). cWdr37 silencing protected against hypoxic stress- or oxidative stress-induced retinal ganglion cell (RGC) injury. cWdr37 silencing alleviated IR-induced retinal neurodegeneration as shown by increased NeuN staining, reduced retinal reactive gliosis, and decreased retinal apoptosis. Collectively, this study provides a novel insight into the pathogenesis of retinal I/R injury. cWdr37 is a promising target for the diagnosis or treatment of I/R-related ocular diseases.

Protective effects of dapagliflozin against oxidative stress-induced cell injury in human proximal tubular cells.

Elevated reactive oxygen species (ROS) in type 2 diabetes cause cellular damage in many organs. Recently, the new class of glucose-lowering agents, SGLT-2 inhibitors, have been shown to reduce the risk of developing diabetic complications; however, the mechanisms of such beneficial effect are largely unknown. Here we aimed to investigate the effects of dapagliflozin on cell proliferation and cell death under oxidative stress conditions and explore its underlying mechanisms. Human proximal tubular cells (HK-2) were used. Cell growth and death were monitored by cell counting, water-soluble tetrazolium-1 (WST-1) and lactate dehydrogenase (LDH) assays, and flow cytometry. The cytosolic and mitochondrial (ROS) production was measured using fluorescent probes (H2DCFDA and MitoSOX) under normal and oxidative stress conditions mimicked by addition of H2O2. Intracellular Ca2+ dynamics was monitored by FlexStation 3 using cell-permeable Ca2+ dye Fura-PE3/AM. Dapagliflozin (0.1-10 μM) had no effect on HK-2 cell proliferation under normal conditions, but an inhibitory effect was seen at an extreme high concentration (100 μM). However, dapagliflozin at 0.1 to 5 μM showed remarkable protective effects against H2O2-induced cell injury via increasing the viable cell number at phase G0/G1. The elevated cytosolic and mitochondrial ROS under oxidative stress was significantly decreased by dapagliflozin. Dapagliflozin increased the basal intracellular [Ca2+]i in proximal tubular cells, but did not affect calcium release from endoplasmic reticulum and store-operated Ca2+ entry. The H2O2-sensitive TRPM2 channel seemed to be involved in the Ca2+ dynamics regulated by dapagliflozin. However, dapagliflozin had no direct effects on ORAI1, ORAI3, TRPC4 and TRPC5 channels. Our results suggest that dapagliflozin shows anti-oxidative properties by reducing cytosolic and mitochondrial ROS production and altering Ca2+ dynamics, and thus exerts its protective effects against cell damage under oxidative stress environment.

A glutathione-triggered precision explosive system for improving tumor chemosensitivity

Stimuli-responsive delivery systems hold promise in cancer treatments. However, their application potential has been limited due to undesirable drug leaking during blood circulation and inefficient therapeutic efficacy in tumors, resulting in undesirable therapeutic outcomes. Herein, we have developed a novel redox-sensitive pegylated phospholipid, termed as DOPE-SS-PEG, which can form a glutathione (GSH)-triggered precision explosive system (GPS) for simultaneously improving circulation stability, tumor specificity, and chemosensitivity, leading to explosive anticancer effects. GPS is constructed of liposomal doxorubicin (DOX) functionalized with DOPE-SS-PEG and MnO2 nanoparticles, which can protect liposome structure in the presence of serum GSH (20 pM), whereas converts to cationic liposome in response to intracellular GSH (10 mM), thereby enhancing circulation stability, tumor specificity, endosomal escape, and cytoplasmic delivery. Importantly, GPS can not only generate oxygen to relieve hypoxia and consequently enhance chemosensitivity, but quench GSH antioxidability to elevate the accruement of intracellular reactive oxygen species (ROS), leading to an explosion of oxidative stress induced cell injury. Particularly, in vivo studies show that GPS selectively accumulates in tumor tissues, effectively inhibits tumor growth, exhibits minimal systemic adverse effects, and consequently prolongs the survival time of tumor-bearing mice. Therefore, GPS is a unique stimuli-responsive treatment with programmed and on-demand drug delivery, as well as explosive therapeutic efficacy, and provides an intelligent anticancer treatment.

Effect of Nardostachys jatamansi DC. on Apoptosis, Inflammation and Oxidative Stress Induced by Doxorubicin in Wistar Rats.

The study aimed to investigate the protective action of jatamansi (Nardostachys jatamansi DC.) against doxorubicin cardiotoxicity. Methanolic extract of jatamansi (MEJ) was prepared and standardized using HPTLC fingerprinting, GC-MS chemoprofiling, total phenolic content, and antioxidant activity in vitro. Further in vivo activity was evaluated using rodent model. Animals were divided into five groups (n = 6) namely control (CNT) (Normal saline), toxicant (TOX, without any treatment), MEJ at low dose (JAT1), MEJ at high dose (JAT2), and standard desferrioxamine (STD). All groups except control received doxorubicin 2.5 mg per Kg intra-peritoneally for 3 weeks in twice a week regimen. After 3 weeks, the blood samples and cardiac tissues were collected from all groups for biochemical and histopathological evaluation. Treatment with MEJ at both dose levels exhibited significant reduction (p < 0.001 vs. toxicant) of serum CK-MB (heart creatine kinase), LDH (Lactate dehydrogenase) & HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) levels, and tissue MDA (melondialdehyde) level; insignificant difference was observed (p > 0.05) in TNF-alpha (tumour necrosis factor), IL-6 (interleukine-6) levels and caspase activity as compared to TOX. Histopathological evaluation of cardiac tissues of different treatment groups further reinforced the findings of biochemical estimation. This study concludes that jatamansi can protect cardiac tissues from oxidative stress-induced cell injury and lipid peroxidation as well as against inflammatory and apoptotic effects on cardiac tissues.

Mangiferin protect oxidative stress against deoxynivalenol induced damages through Nrf2 signalling pathways in endothelial cells.

Several cereal grains contain a mycotoxin food contaminant called deoxynivalenol (DON), which presents a significant health risk as it is one of the most commonly found mycotoxins. The current paper examines the ameliorative effect of mangiferin (MAN) in vascular endothelial cells induced through activating the Nrf2 signalling pathway on dietary DON-induced oxidative changes. The study infers that the intercellular reactive oxygen species (ROS) levels and malondialdehyde decrease due to MAN. Other effects include in human umbilical vein endothelial cells (HUVECs), the oxidative stress-induced cell damage is reduced due to protective effects and superoxide dismutase (SOD), and catalase (CAT) activities also reveal an improvement. In HUVECs, the Nrf2-regulated antioxidant enzyme genes' expression is activated by Nrf2 nuclear translocation induction and this activity suppresses the oxidative stress damage. The genes in HUVECs include HO-1 and NQO1. Moreover, in HUVECs, the nucleus translocation of Nrf2 reduces the Nrf2, HO-1, whereas NQO1 expression decreases the cytoprotective effects against oxidative stress reduce with the rejection of Nrf2 with siRNA. This paper pioneers in inferring that oxidative stress-induced HUVECs' cell injury is suppressed by MAN through Nrf2, signalling pathway activation.