Oxidative Stress-related Signaling Pathways Research Articles

Trillin Protects Against Bleomycin-Induced Pulmonary Fibrosis via Suppressing Oxidative Stress and IL-1β/NLRP3 Inflammasome Positive Cycle

Background Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fibrotic interstitial lung disease. Trillin, an active saponin component isolated from Trillium tschonoskii Maxim, exhibits various pharmacological properties. This study aimed to investigate the preventive effects of Trillin on bleomycin (BLM)-induced IPF and elucidate its underlying mechanisms. Methods BLM was administered via intratracheal injection to C57BL/6J mice to establish an IPF model. Different concentrations of Trillin were then administered as treatments. Network pharmacology and molecular docking approaches were employed to predict potential Trillin targets against IPF. A combination of histopathological examination, immunohistochemical analysis, Western Blotting, and other molecular biological techniques were utilized to assess Trillin's protective effect on BLM-induced IPF and to investigate underlying pathways. Results Trillin effectively inhibited lung tissue injury induced by BLM in mice, moderated inflammation and oxidative stress-related signaling pathways, and reduced the expression of IPF-associated proteins such as TGF-β1 and α-SMA. Network pharmacology analysis identified 18 core Trillin-IPF target genes. Molecular docking analysis suggested that pro-inflammatory cytokines IL-1β, IL-2, and TNF-α have high binding affinity with Trillin, suggesting their potential as anti-IPF targets. Additionally, experimental verification confirmed that Trillin suppressed NLRP3 inflammasome activation by reducing IL-1β release. Conclusions This study demonstrates that Trillin effectively reduces oxidative stress and blocks the IL-1β/NLRP3 inflammasome positive feedback loop, providing protection against BLM-induced IPF. Consequently, our research underscores the potential of Trillin as a promising therapeutic agent for IPF and lays a theoretical foundation for its future clinical development and application in treating BLM-induced IPF.

Gut microbiota-derived trimethylamine N-Oxide: a novel target for the treatment of preeclampsia

ABSTRACT Pre-eclampsia (PE) is the most common complication of pregnancy and seriously threatens the health and safety of the mother and child. Studies have shown that an imbalance in gut microbiota can affect the progression of PE. Trimethylamine N-oxide (TMAO) is an intestinal microbiota-derived metabolite that is thought to be involved in the occurrence of PE; however, its causal relationship and mechanism remain unclear. In this clinical cohort study, including 28 patients with eclampsia and 39 matched healthy controls, fecal samples were collected for 16S rRNA gene sequencing, and serum was collected for targeted metabolomics research. The results showed that the level of TMAO and the abundance of its source bacteria had significantly increased in patients with PE, and were positively correlated with the clinical progression of PE. Fecal microbiota transplantation (FMT) was applied to an antibiotic-depleted-treated mouse model and targeted inhibition of TMAO. The results of the FMT experiment revealed that mice that received fecal microbiota transplantation from patients with PE developed typical PE symptoms and increased oxidative stress and inflammatory damage, both of which were reversed by 3,3-Dimethyl-1-butanol (DMB), a TMAO inhibitor, which also improved pregnancy outcomes in the model mice. Similar results were obtained in the classical NG-Nitroarginine methyl ester (L-NAME) induced PE mouse model. Mechanistically, TMAO promotes the progression of PE by regulating inflammatory and oxidative stress-related signaling pathways, affecting the migration and angiogenesis of vascular endothelial cells, as well as the migration and invasion of trophoblast cells. Our results reveal the role and mechanism of gut microbiota and TMAO in the progression of PE, provides new ideas for exploring the pathogenesis and therapeutic targets of PE, and determines the potential application value of TMAO as a target for PE intervention.

Unravelling the Antioxidant Potential of Resveratrol and Quercetin in Animal Models: A Comprehensive Review


 Resveratrol and quercetin are naturally occurring polyphenolic compounds widely studied for their potential health benefits, particularly their antioxidant properties. This abstract provides an overview of the extensive research conducted on resveratrol and quercetin as antioxidants in animal models, highlighting their mechanisms of action and therapeutic potential. Animal models, such as rodents, have been instrumental in elucidating the oxidative stress pathway and evaluating the efficacy of various antioxidants. Resveratrol and quercetin have demonstrated significant antioxidant effects in animal models through multiple mechanisms. These include direct scavenging of reactive oxygen species (ROS), upregulation of endogenous antioxidant enzymes, inhibition of lipid peroxidation, and modulation of oxidative stress-related signaling pathways.

Oxidative Stress-Related Signaling Pathways Predict Oocytes' Fertilization In Vitro and Embryo Quality.

Oocyte development and fertilization are largely influenced by the microenvironment of the follicular fluid (FF), and the exploration of its molecular/metabolic composition may help in improving in vitro fertilization (IVF) outcomes. Here, the concentrations of molecules related to oxidative stress/inflammation were measured in FF from follicles at oocyte retrieval during IVF. Here, the FF antioxidant potential was correlated with the number of retrieved/mature oocytes and the number of fertilized ones. FF collected from the follicles of normal fertilized oocytes presented an elevated antioxidant capability, lower levels of pro-inflammatory molecules (i.e., IL-6, IL-8, IL-12, TGF-β, and HIF-1α), and a higher IL-10 concentration. FF samples from follicles at oocyte retrieval that resulted in top-quality embryos displayed a peculiar antioxidant capability and a further decrease in proinflammatory molecules when compared with FF, giving rise to poor-quality embryos. Finally, pro-inflammatory molecules were lower and accompanied by a high antioxidant capability in samples giving rise to successful embryo implantation. The antioxidant capability and IL-10 displayed a good predictive ability for fertilization and embryo quality. Overall, our data showed the great influence of oxidative stress on the oocytes' fertilization, and shed light on the importance of controlling the inflammatory and oxidative status of FF to obtain good-quality embryos with significant implantation potential.

Natural products of traditional Chinese medicine treat atherosclerosis by regulating inflammatory and oxidative stress pathways.

Atherosclerosis (AS) is a prevalent arteriosclerotic vascular disease that forms a pathological basis for coronary heart disease, stroke, and other diseases. Inflammatory and oxidative stress responses occur throughout the development of AS. Treatment for AS over the past few decades has focused on administering high-intensity statins to reduce blood lipid levels, but these inevitably damage liver and kidney function over the long term. Natural medicines are widely used to prevent and treat AS in China because of their wide range of beneficial effects, low toxicity, and minimal side effects. We searched for relevant literature over the past 5 years in databases such as PubMed using the keywords, “atherosclerosis,” “traditional Chinese medicine,” “natural medicines,” “inflammation,” and “oxidative stress.” We found that the PI3K/AKT, TLR4, JAK/STAT, Nrf2, MAPK, and NF-κB are the most relevant inflammatory and oxidative stress pathways in AS. This review summarizes studies of the natural alkaloid, flavonoid, polyphenol, saponin, and quinone pathways through which natural medicines used to treat AS. This study aimed to update and summarize progress in understanding how natural medicines treat AS via inflammatory and oxidative stress-related signaling pathways. We also planned to create an information base for the development of novel drugs for future AS treatment.

High-Fat Diet-Induced Renal Proximal Tubular Inflammatory Injury: Emerging Risk Factor of Chronic Kidney Disease.

Nowadays, with the improvements in living standards and changes in living habits, high-fat diet (HFD) has become much more common in the populations worldwide. Recent studies have shown that HFD could induce lipid accumulation, and structural and functional abnormalities, accompanied by the release of large amounts of pro-inflammatory cytokines, in proximal tubular epithelial cells (PTECs). These findings indicate that, as an emerging risk factor, PTEC injury-induced by HFD may be closely related to inflammation; however, the potential mechanisms underlying this phenomenon is still not well-known, but may involve the several inflammatory pathways, including oxidative stress-related signaling pathways, mitochondrial dysfunction, the myeloid differentiation factor 2/Toll like receptor 4 (MD2/TLR4) signaling pathway, the ERK1/2-kidney injury molecule 1 (KIM-1)-related pathway, and nuclear factor-κB (NF-κB) activation, etc., and the detailed molecular mechanisms underlying these pathways still need further investigated in the future. Based on lipid abnormalities-induced inflammation is closely related to the development and progression of chronic kidney disease (CKD), to summarize the potential mechanisms underlying HFD-induced renal proximal tubular inflammatory injury, may provide novel approaches for CKD treatment.

Extracellular Vesicles as Natural Delivery Carriers Regulate Oxidative Stress Under Pathological Conditions.

Extracellular vesicles are cellular secretory particles that can be used as natural drug delivery carriers. They have successfully delivered drugs including chemotherapeutics, proteins, and genes to treat various diseases. Oxidative stress is an abnormal physiological phenomenon, and it is associated with nearly all diseases. In this short review, we summarize the regulation of EVs on oxidative stress. There are direct effects and indirect effects on the regulation of oxidative stress through EVs. On the one hand, they can deliver antioxidant substances or oxides to recipient cells, directly relieving or aggravating oxidative stress. On the other hand, regulate factors of oxidative stress-related signaling pathways can be delivered to recipient cells by the mediation of EVs, realizing the indirect regulation of oxidative stress. To the best of our knowledge, however, only endogenous drugs have been delivered by EVs to regulate oxidative stress till now. And the heterogeneity of EVs may complicate the regulation of oxidative stress. Therefore, this short review aims to draw more attention to the EVs-based regulation of oxidative stress, and we hope excellent EVs-based delivery carriers that can deliver exogenous drugs to regulate oxidative stress can be exploited.

Research advances in monomers of Chinese herbs in treatment of liver fibrosis by regulating oxidative stress

Liver fibrosis, a common pathological process of most types of chronic liver diseases, is caused by the excessive deposition of extracellular matrix proteins after chronic liver injury. An increasing number of evidence has shown that oxidative stress is closely associated with the development and progression of liver fibrosis and is involved in the pathological process of liver fibrosis caused by various factors. With natural constituents and a clear structure, Chinese herbal monomers herbs have achieved a marked clinical effect in the treatment of liver fibrosis. This article reviews the research advances in monomers of Chinese herbs in the treatment of liver fibrosis by regulating oxidative stress-related signaling pathways.

Use of a Systematic Pharmacological Methodology to Explore the Mechanism of Shengmai Powder in Treating Diabetic Cardiomyopathy.

BackgroundCardiovascular complications, such as diabetic cardiomyopathy (DCM), are the leading cause of death in diabetic patients. Shengmai Powder (SMP) was found to have cardioprotective effects.Material/MethodsBased on the systematic pharmacological methodology, this research determined the genes of DCM and the known targets of SMP, predicted potential compounds and targets of SMP, constructed networks for DCM and SMP, and performed network analysis.ResultsFive network were constructed: (1) the DCM gene PPI network; (2) the Compound-compound target network of SMP; (3) the SMP-DCM PPI network; (4) the Compound-known target network of SMP; (5) and the SMP known target-DCM PPI network. Several DCM and treatment related targets, clusters, signaling pathways, and biological processes were found.ConclusionsSMP is able to regulate glycometabolism-related, lipid metabolism-related, inflammatory response-related, oxidative stress-related signaling pathways, and biological processes and targets, which suggests that SMP may have a therapeutic effect on DCM.

Protein Carbonylation in Patients with Myelodysplastic Syndrome: An Opportunity for Deferasirox Therapy.

Control of oxidative stress in the bone marrow (BM) is key for maintaining the interplay between self-renewal, proliferation, and differentiation of hematopoietic cells. Breakdown of this regulation can lead to diseases characterized by BM failure such as the myelodysplastic syndromes (MDS). To better understand the role of oxidative stress in MDS development, we compared protein carbonylation as an indicator of oxidative stress in the BM of patients with MDS and control subjects, and also patients with MDS under treatment with the iron chelator deferasirox (DFX). As expected, differences in the pattern of protein carbonylation were observed in BM samples between MDS patients and controls, with an increase in protein carbonylation in the former. Strikingly, patients under DFX treatment had lower levels of protein carbonylation in BM with respect to untreated patients. Proteomic analysis identified four proteins with high carbonylation levels in MDS BM cells. Finally, as oxidative stress-related signaling pathways can modulate the cell cycle through p53, we analyzed the expression of the p53 target gene p21 in BM cells, finding that it was significantly upregulated in patients with MDS and was significantly downregulated after DFX treatment. Overall, our results suggest that the fine-tuning of oxidative stress levels in the BM of patients with MDS might control malignant progression.

1-O-Hexyl-2,3,5-Trimethylhydroquinone Ameliorates l-DOPA-Induced Cytotoxicity in PC12 Cells.

1-O-Hexyl-2,3,5-trimethylhydroquinone (HTHQ) has previously been found to have effective anti-oxidant and anti-lipid-peroxidative activity. We aimed to elucidate whether HTHQ can prevent dopaminergic neuronal cell death by investigating the effect on l-DOPA-induced cytotoxicity in PC12 cells. HTHQ protected from both l-DOPA-induced cell death and superoxide dismutase activity reduction. When assessing the effect of HTHQ on oxidative stress-related signaling pathways, HTHQ inhibited l-DOPA-induced phosphorylation of sustained extracellular signal-regulated kinases (ERK1/2), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK1/2). HTHQ also normalized l-DOPA-reduced Bcl-2-associated death protein (Bad) phosphorylation and Bcl-2-associated X protein (Bax) expression, promoting cell survival. Taken together, HTHQ exhibits protective effects against l-DOPA-induced cell death through modulation of the ERK1/2-p38MAPK-JNK1/2-Bad-Bax signaling pathway in PC12 cells. These results suggest that HTHQ may show ameliorative effects against oxidative stress-induced dopaminergic neuronal cell death, although further studies in animal models of Parkinson’s disease are required to confirm this.

The Role of Traditional Chinese Medicine in the Regulation of Oxidative Stress in Treating Coronary Heart Disease.

Oxidative stress has been closely related with coronary artery disease. In coronary heart disease (CHD), an excess of reactive oxygen species (ROS) production generates endothelial cell and smooth muscle functional disorders, leading to a disequilibrium between the antioxidant capacity and prooxidants. ROS also leads to inflammatory signal activation and mitochondria-mediated apoptosis, which can promote and increase the occurrence and development of CHD. There are several kinds of antioxidative and small molecular systems of antioxidants, such as β-carotene, ascorbic acid, α-tocopherol, and reduced glutathione (GSH). Studies have shown that antioxidant treatment was effective and decreased the risk of CHD, but the effect of the treatment varies greatly. Traditional Chinese medicine (TCM) has been utilized for thousands of years in China and is becoming increasingly popular all over the world, especially for the treatments of cardiovascular diseases. This review will concentrate on the evidence of the action mechanism of TCM in preventing CHD by modulating oxidative stress-related signaling pathways.

Effects of Low Salt Diet on Gene Expression in Dog Heart

Low-salt(LS) always be abided as dietary principle by hypertension patients. However, recent studies found that the incidence of cardiopathy and stroke increases in subjects with LS diet(<3g/d), meanwhile, LS can accelerate the development of atherosclerosis. It is essential to study deeply on the relationship between the amount of salt intake and cardiovascular diseases. We performed an analysis to explore the possible molecular mechanism of salt-induced cardiovascular disease. Microarray datasets (GSE17149) of heart tissue from LS diet dogs was obtained from NCBI’s GEO Database. The data was analyzed by QOE, STRING and Genclip 2.0. The protein-protein interactions (PPI) networks of the differentially expressed genes(DEGs, p<0.05, q<0.05, Fold change>2) between the LS group and control group (normal diet) were conducted to screen the key biomarkers between the two groups. Compared with the control group, the gene expression profile of heart tissue from dogs was changed in the LS group(0.05% of sodium chloride, approximately 150 mg/d). 1343 (3.12%) DEGs were found from 43035 genes in total. The results also revealed that NFKBIA and NR1H2 were the cores of the PPI networks, which were mainly related to reduce the function of macrophage-derived foam cells and to promote cholesterol discharge and decomposition. The signaling pathways such as MAPK, PI3K-Akt, NF-kappa B were activated when the dogs received LS diet, which resulted in lower risk of cardiovascular disease through anti-apoptosis, anti-inflammation, anti-oxidative stress, et al. The gene expression of heart tissue in LS diet dogs is significantly changed and LS diet may reduce the risk of cardiovascular disease by up-regulating the expression of NFKBIA, NR1H2 and oxidative stress-related signaling pathways. More rigorous and independent experiments are needed to validate the conclusions of the present study.

Tributyltin exposure at noncytotoxic doses dysregulates pancreatic β-cell function in vitro and in vivo.

Tributyltin (TBT) is an endocrine disruptor. TBT can be found in food and in human tissues and blood. Several animal studies revealed that organotins induced diabetes with decreased insulin secretion. The detailed effect and mechanism of TBT on pancreatic β-cell function still remain unclear. We investigated the effect and mechanism of TBT exposure at noncytotoxic doses relevant to human exposure on β-cell function in vitro and in vivo. The β-cell-derived RIN-m5F cells and pancreatic islets from mouse and human were treated with TBT (0.05-0.2μM) for 0.5-4h. Adult male mice were orally exposed to TBT (25μg/kg/day) with or without antioxidant N-acetylcysteine (NAC) for 1-3 weeks. Assays for insulin secretion and glucose metabolism were carried out. Unlike previous studies, TBT at noncytotoxic concentrations significantly increased glucose-stimulated insulin secretion and intracellular Ca2+ ([Ca2+]i) in β-cells. The reactive oxygen species (ROS) production and phosphorylation of protein kinase C (PKC-pan) and extracellular signal-regulated kinase (ERK)1/2 were also increased. These TBT-triggered effects could be reversed by antiestrogen ICI182780 and inhibitors of ROS, [Ca2+]i, and PKC, but not ERK. Similarly, islets treated with TBT significantly increased glucose-stimulated insulin secretion, which could be reversed by ICI182780, NAC, and PKC inhibitor. Mice exposed to TBT for 3 weeks significantly increased blood glucose and plasma insulin and induced glucose intolerance and insulin resistance, which could be reversed by NAC. These findings suggest that low/noncytotoxic doses of TBT induce insulin dysregulation and disturb glucose homeostasis, which may be mediated through the estrogen receptor-regulated and/or oxidative stress-related signaling pathways.

Puerarin Suppresses Angiotensin II-Induced Cardiac Hypertrophy by Inhibiting NADPH Oxidase Activation and Oxidative Stress-Triggered AP-1 Signaling Pathways.

To examine the effects of puerarin (Pue) on angiotensin II (AngII)-induced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and oxidative stress-related signaling pathways in the hypertrophic response of cardiomyocytes. Primary cardiomyocytes of neonatal C57BL/6J mice were pretreated with Pue (50, 100 μmol/L) and were then stimulated with AngII 1 μmol/L. NADPH oxidase activity and reactive oxygen species (ROS) levels were measured by lucigenin-enhanced chemiluminescence assay and flow cytometry. Western blotting was used to detect the distribution of the oxidase subunits, extracellular signal-regulated kinase (ERK1/2) and c-jun N-terminal kinase (JNK1/2) activation, and an electrophoretic mobility shift assay (EMSA) was performed to analyze the DNA binding activity of activator protein-1 (AP-1). Adult C57BL/6J mice were infused with AngII and were administered with Pue (100, 200 mg·kg-1·d-1) for 15 d. After the treatment, systolic blood pressure (SBP) and left ventricular wall thickness were examined. The ratios of heart weight to body weight (HW/BW) and left ventricular weight to body weight (LVW/BW) were measured, and heart morphometry was assessed. In vitro, Pue dose-dependently blocked the phosphorylation of ERK1/2 and JNK1/2 and eventually abolished AP-1 binding activity through the inhibition of ROS production. Further studies revealed that AngII treatment resulted in increased NADPH oxidase activity, which was suppressed by Pue via the disruption of Rac1 activation and membrane translocation of oxidase subunits. In vivo, Pue attenuated cardiac hypertrophy, as evaluated by decreased HW/BW, LVW/BW, myocyte surface area, and left ventricular wall thickness. The anti-hypertrophic mechanism of Pue occurred by blocking Rac1-dependent NADPH oxidase activation and downstream redox-sensitive AP-1 signaling pathways.

Radiation persistently promoted oxidative stress, activated mTOR via PI3K/Akt, and downregulated autophagy pathway in mouse intestine

While acute effects of toxic radiation doses on intestine are well established, we are yet to acquire a complete spectrum of sub-lethal radiation-induced chronic intestinal perturbations at the molecular level. We investigated persistent effects of a radiation dose (2Gy) commonly used as a daily fraction in radiotherapy on oxidants and anti-oxidants, and autophagy pathways, which are interlinked processes affecting intestinal homeostasis. Six to eight weeks old C57BL/6J mice (n=10) were exposed to 2Gy γ-ray. Mice were euthanized two or twelve months after radiation, intestine surgically removed, and flushed using sterile PBS. Parts of the intestine from jejunal–ilial region were fixed, frozen, or used for intestinal epithelial cell (IEC) isolation. While oxidant levels and mitochondrial status were assessed in isolated IEC, autophagy and oxidative stress related signaling pathways were probed in frozen and fixed samples using PCR-based expression arrays and immunoprobing. Radiation exposure caused significant alterations in the expression level of 26 autophagy and 17 oxidative stress related genes. Immunoblot results showed decreased Beclin1 and LC3-II and increased p62, PI3K/Akt, and mTOR. Flow cytometry data showed increased oxidant production and compromised mitochondrial integrity in irradiated samples. Immunoprobing of intestinal sections showed increased 8-oxo-dG and nuclear PCNA, and decreased autophagosome marker LC3-II in IEC after irradiation. We show that sub-lethal radiation could persistently downregulate anti-oxidants and autophagy signaling, and upregulate oxidant production and proliferative signaling. Radiation-induced promotion of oxidative stress and downregulation of autophagy could work in tandem to alter intestinal functions and have implications for post-radiation chronic gastrointestinal diseases.

Peroxisomal metabolism and oxidative stress

Peroxisomes are ubiquitous and multifunctional organelles that are primarily known for their role in cellular lipid metabolism. As many peroxisomal enzymes catalyze redox reactions as part of their normal function, these organelles are also increasingly recognized as potential regulators of oxidative stress-related signaling pathways. This in turn suggests that peroxisome dysfunction is not only associated with rare inborn errors of peroxisomal metabolism, but also with more common age-related diseases such as neurodegeneration, type 2 diabetes, and cancer. This review intends to provide a comprehensive picture of the complex role of mammalian peroxisomes in cellular redox metabolism. We highlight how peroxisomal metabolism may contribute to the bioavailability of important mediators of oxidative stress, with particular emphasis on reactive oxygen species. In addition, we review the biological properties of peroxisome-derived signaling messengers and discuss how these molecules may mediate various biological responses. Furthermore, we explore the emerging concepts that peroxisomes and mitochondria share an intricate redox-sensitive relationship and cooperate in cell fate decisions. This is particularly relevant to the observed demise of peroxisome function which accompanies cellular senescence, organismal aging, and age-related diseases.

Taurine ameliorates alloxan-induced diabetic renal injury, oxidative stress-related signaling pathways and apoptosis in rats

Hyperglycemia-induced oxidative stress plays a vital role in the progression of diabetic nephropathy. The renoprotective nature of taurine has also been reported earlier; but little is known about the mechanism of this beneficial action. The present study has, therefore, been carried out to explore in detail the mechanism of the renoprotective effect of taurine under diabetic conditions. Diabetes was induced in rats by alloxan (single i.p. dose of 120 mg/kg body weight) administration. Taurine was administered orally for 3 weeks (1% w/v in drinking water) either from the day on which alloxan was injected or after the onset of diabetes. Alloxan-induced diabetic rats showed a significant increase in plasma glucose, enhanced the levels of renal damage markers, plasma creatinine, urea nitrogen and urinary albumin. Diabetic renal injury was associated with increased kidney weight to body weight ratio and glomerular hypertrophy. Moreover, it increased the productions of reactive oxygen species, enhanced lipid peroxidation and protein carbonylation in association with decreased intracellular antioxidant defense in the kidney tissue. In addition, hyperglycemia enhanced the levels of proinflammatory cytokins (TNF-α, IL-6, IL-1β) and Na(+)--K(+)-ATPase activity with a concomitant reduction in NO content and eNOS expression in diabetic kidney. Investigation of the oxidative stress-responsive signaling cascades showed the upregulation of PKCα, PKCβ, PKCε and MAPkinases in the renal tissue of the diabetic animals. However, taurine administration decreased the elevated blood glucose and proinflammatory cytokine levels, reduced renal oxidative stress (via decrease in xanthine oxidase activity, AGEs formation and inhibition of p47phox/CYP2E1 pathways), improved renal function and protected renal tissue from alloxan-induced apoptosis via the regulation of Bcl-2 family and caspase-9/3 proteins. Taurine supplementation in regular diet could, therefore, be beneficial to regulate diabetes-associated renal complications.

Differential Inhibitory Effects of Salvianolic Acids on Activation of Rat Hepatic Stellate Cells by Platelet-Derived Growth Factor

Platelet-derived growth factor (PDGF) induces cell proliferation together with oxidative stress. The present study investigated the effects of salvianolic acid A (Sal A) and B (Sal B) on the PDGF-induced signaling cascades in hepatic stellate cells (HSCs). HSC-T6, a rat hepatic stellate cell line, was stimulated with PDGF (10 ng/mL). The inhibitory effects of Sal A and B on oxidative stress-related signaling pathways were assessed in vitro. The protein levels were measured by Western blotting. FACS analysis was applied to detect the thioredoxin (Trx) level. Sal A and B showed different inhibitory abilities on the PDGF-related pathway. Sal A inhibited 70-kDa ribosomal S6 kinase (p70(s6k)) and associated proteins. Sal B attenuated PDGF-induced c-jun-N-terminal kinase (JNK), p38, and PKC- δ phosphorylations. Both Sal A and B diminished the activation of PKD, Trx, heme-oxygenase (HO)-1, and Nrf2. Taken together, our results showed that Sal A and B attenuated PDGF-induced ROS formation in HSCs, possibly through different signaling pathways.

α-pinene triggers oxidative stress and related signaling pathways in A549 and HepG2 cells

The volatile organic compounds (VOCs) -dlimonene, α-pinene, and isoprene-are widely used in scented products including food flavorings, air fresheners, and cosmetics. The effects of these VOCs on cell viability, oxidative stress generation, and the related molecular events were investigated in A549 and HepG2 cells. α-Pinene induced cell death, reactive oxygen species (ROS) generation, and reporter gene activities of antioxidant response element (ARE), activator protein 1 (AP-1), and nuclear factor (NF)-κB. α-Pinene stimulated the redoxsensitive transcription factors such as nuclear factor E2-related factor 2 (Nrf2) and NF-κB. Their down stream targets including heme oxygenase 1, inducible nitric oxide synthase, and cyclooxygenase 2 also increased after treatment with α-pinene. Moreover, α-pinene-induced oxidative stress-related signaling pathways could be connected by mitogen-activated protein kinases. Conversely, α-pinene-mediated cell death, ROS formation, and AP-1 induction were inhibited by an antioxidant, N-acetyl-l-cysteine. Thus, α-pinene can induce the cell death possibly by modulating oxidative stress-related signaling pathways which can be reversed by an antioxidant treatment.