Malondialdehyde Generation Research Articles

Effects of electroacupuncture with dexmedetomidine on myocardial ischemia/reperfusion injury in rats.

To investigate the protective effect of electroacupuncture combined with dexmedetomidine (EA + Dex) on oxidative stress injury in myocardial ischemia/reperfusion (I/R) rats. A total of 50 male Sprague-Dawley (SD) rats were randomly divided into 5 groups: sham operation (sham group); I/R group; dexmedetomidine group (Dex group); electroacupuncture group (EA group); and EA + Dex group. The myocardial I/R model was established. The EA group received EA at the Neiguan acupoint [pericardium 6 (PC6)] every day for 1 week before modeling. Rats in the EA + Dex group received EA at PC6 every day for 1 week before modeling, and intraperitoneal injection of Dex was performed 15 minutes before modeling. Dex was injected intraperitoneally in the Dex group 15 minutes before modeling. The rats were sacrificed 1 hour after reperfusion, and myocardial tissue was obtained to measure the myocardial infarction area. The myocardial tissue pathologic changes were shown by hematoxylin and eosin (HE) staining, and the superoxide dismutase (SOD), malondialdehyde (MDA), adenosine triphosphate (ATP), and reactive oxygen species (ROS) content in serum was determined. Compared with the sham group, the myocardial infarction area was significantly increased (P<0.01), SOD and ATP content was significantly decreased (P<0.01), and MDA and ROS content was significantly increased (P<0.01) in the I/R group; this change was significantly reduced in the Dex, EA, and EA + Dex groups (P<0.01). The indicators in the EA + Dex group were better than those in the EA and Dex groups (P<0.05). There was no significant change in the above indices in the Dex group compared with the EA group (P>0.05). EA + Dex pretreatment improved the damage of myocardial I/R by increasing SOD and ATP content and reducing the generation of MDA and ROS in an oxygen-free radical system.

Damage prevention effect of milk-derived peptides on UVB irradiated human foreskin fibroblasts and regulation of photoaging related indicators

Long-term exposure to UVB can trigger acute inflammation of the skin and lead to skin photoaging. To scrutinize the anti-photoaging functions of peptides obtained from milk, the physicochemical including molecular weight and amino acid compositions were first analyzed. Totally 267 peptides were screened out and identified by PEAKS X software, and then evaluated through Peptide Ranker and BIOPEP-UMW. Six peptides with the highest antioxidant ability and relative abundance were selected. This study was then conducted in UVB-damaged human foreskin fibroblasts with proadministration of peptides. The results indicated that at concentrations of 0.08–0.10 mg/mL, milk-derived peptides could realize a damage prevention effect through inhibiting the generation of reactive oxygen species (ROS) and lipid peroxidation malondialdehyde (MDA). Also, these peptides were found to promote the photoaging related enzyme activities of superoxide dismutase (SOD) and catalase (CAT), while to block the production of matrix metalloproteinases-1. Through this study, we found that milk-derived peptide mixture is effective in preventing photoaging damage. Milk-derived peptides found in this study could serve as raw materials for future development of antioxidant functional foods.

Isoliquiritigenin attenuates emodin-induced hepatotoxicity in vivo and in vitro through Nrf2 pathway

Emodin (EMO), the main bioactive component of Polygonum multiflorum, Rheum palmatum, Aloe vera and Cassia acutifolia, can cause severe hepatotoxicity. Isoliquiritigenin (ISL), a flavonoid compound from the Glycyrrhiza, has been reported to be the most potent antioxidant response element (ARE)-luciferase inducer among the main components of licorice. But the protective effect and underlying mechanism of ISL on liver injury induced by EMO has not been reported. This study aims to explore the role of nuclear transcription factor 2 (Nrf2) in EMO-induced hepatotoxicity and the protective effect of ISL. EMO treatment caused cytotoxicity in L-02 cells. Combined treatment of EMO with ISL effectively reversed changes in cell viability, reduced reactive oxygen species (ROS) generation and malondialdehyde (MDA) generation, enhanced the levels of glutathione (GSH) and super oxide dismutase (SOD) induced by EMO in L-02 cells. Furthermore, ISL could also phosphorylate mitogen-activated protein kinases (MAPKs) and up-regulate Kelth-like ECH-associated protein (Keap1). The pathways of MAPKs and Keap1 lead to the separation of Keap1 and Nrf2. Free Nrf2 transferred to the nucleus and enhanced the expression of phase II detoxification enzymes. In conclusion, our results are the first to highlight the beneficial role and relevant mechanisms of ISL in EMO-induced liver injury and provide novel insight into its application.

Protective effect and mechanism of SeMet-Pro-Ser on K2Cr2O7-induced toxicity in L-02 hepatocytes

SeMet-Pro-Ser (Se-MPS), identified from selenium-enriched brown rice protein hydrolysates, shows strong free radical scavenging capacities and hexavalent chromium [Cr(VI)] reduction activity. This study explored the protective effect and mechanism of Se-MPS on potassium dichromate (K2Cr2O7)-induced toxicity in L-02 hepatocytes. Exposure of L-02 hepatocytes to K2Cr2O7 drastically decreased the cell viability and caused cell apoptosis, which was effectively suppressed by Se-MPS treatment in a dose-dependent manner. Se-MPS significantly prevented the increase of reactive oxygen species (ROS) and malondialdehyde (MDA) generation, the decrease of antioxidant enzyme activities; and the depletion of reduced glutathione (GSH) induced by K2Cr2O7. In addition, Se-MPS could alleviate K2Cr2O7- induced apoptosis as assessed by mitochondrial membrane potential and caspase family. The expression levels of apoptosis-related proteins Bax and cytochrome C were significantly downregulated, and anti-apoptotic protein Bcl-2 was significantly upregulated in the Se-MPS plus K2Cr2O7 group. This study provided further insights into Se-MPS in resisting K2Cr2O7-induced cytotoxicity.

Gum tragacanth-sodium alginate active coatings containing epigallocatechin gallate reduce hydrogen peroxide content and inhibit lipid and protein oxidations of large yellow croaker (Larimichthys crocea) during superchilling storage

The active coatings supplemented with epigallocatechin gallate (EGCG) (0.16 %, 0.32 %, and 0.64 %, respectively) combined with superchilling storage (−3 ± 0.2 °C) were used to reduce hydrogen peroxide (H2O2) content, and inhibit lipid and protein oxidations of large yellow croaker during 42 days of superchilling storage. EGCG coatings delayed lipid and protein oxidations by inhibiting the generation of H2O2, malondialdehyde (MDA) and carbonyl groups, and maintaining a higher Ca2+-ATPase activity and sulfhydryl content. We also observed that EGCG treatments maintained myofibrillar organized secondary structure by keeping higher α-helix content, and also stabilized tertiary structure during superchilling storage. Low-field nuclear magnetic resonance (LF-NMR) revealed that EGCG treatments might improve the association of water molecules with protein for fixed water. In addition, sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE) and scanning electron microscope (SEM) images both showed that these treatments could delay the myofibrillar degradation of fresh fish. Overall, we report that the active coatings containing EGCG treatments protect the lipid and protein of large yellow croaker during superchilling storage.

Octopus-derived antioxidant peptide protects against hydrogen peroxide-induced oxidative stress in IEC-6 cells.

This study aims to find antioxidant peptides from octopus protein hydrolyzates and verify the protective effects against H2O2-induced oxidative stress in IEC-6 cells. After the alcalase hydrolysate was ultrafiltrated, purified by Sephadex G-25 gel fractionation and semipreparative reversed-phase high-performance liquid chromatography (RP-HPLC), 16 peptides were identified, and chemically synthesized. In particular, the peptides AQNY, AMMLAW, FEGAW, GGAW, VDTVVCVW, and VVCLW showed better oxygen radical absorbance capacity (ORAC) and ABTS radical scavenging capacity. Among them, the smallest-molecular-weight peptide GGAW exhibited the best antioxidant activity. Furthermore, GGAW protected IEC-6 cells from H2O2-induced oxidative damage by significantly reducing the generation of reactive oxygen species (ROS), malondialdehyde (MDA), and lactate dehydrogenase (LDH), and increasing the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), thereby improving cell viability. These results indicated that the peptide GGAW possessed the antioxidant capacity to prevent oxidative stress damage.

Exogenous Melatonin Treatment Induces Disease Resistance against Botrytis cinerea on Post-Harvest Grapes by Activating Defence Responses.

Botrytis cinerea seriously affects the value of post-harvest grapes. Melatonin can act as an exogenous regulator in the resistance of exogenous pathogens due to its antioxidant activity. An artificial inoculation trial was conducted to research the induced resistance mechanism of melatonin treatment using the table grape “Muscat Hamburg” (Vitis vinifera L. cv). Grapes were immersed with 0.02, 0.2, and 2 mmol/L melatonin, followed by B. cinerea suspension injections after 48 h. The results showed that the mycelial growth and spore germination of B. cinerea was not significantly inhibited by melatonin at different concentrations (0.02–2 mmol/L). However, post-harvest melatonin treatment inhibited the increase of disease incidence and severity of grey mould, induced the synthesis and accumulation of total phenols and flavonoids, reduced malondialdehyde generation, and inhibited an increase in cell membrane permeability. Meanwhile, defensive enzyme activities, including superoxide dismutase (SOD), peroxidize (POD), catalase (CAT), phenylalanine ammonia-lyase (PAL), polyphenol oxidase (PPO), chitinase (CHI), and β-1,3-glucanase, were significantly increased in fruits treated with exogenous melatonin. These results suggested that exogenous melatonin treatment could activate defence responses to combat the infection of B. cinerea in post-harvest grapes.

CircSCAPER knockdown attenuates IL-1β-induced chondrocyte injury by miR-127-5p/TLR4 axis in osteoarthritis

Purpose Osteoarthritis (OA) is a chronic inflammatory degenerative disease characterized by articular cartilage degradation. Circular RNAs have been shown to play significant roles in OA process. Herein, this work aimed to investigate the potential role and mechanism of circSCAPER in OA progression. Methods Levels of circSCAPER, miR-127-5p and toll-like receptor 4 (TLR4) were detected by qRT-PCR or western blotting. Cell apoptosis was determined by flow cytometry. The expression of Aggrecan and Matrix metallopeptidase was examined using western blot to assess extracellular matrix (ECM) degradation. Inflammatory response and oxidative stress were determined by measuring the release of inflammatory factors, along with the generation of intracellular reactive oxygen species and malondialdehyde. The interaction between miR-127-5p and circSCAPER or TLR4 was determined by dual-luciferase reporter, RNA immunoprecipitation and pull-down assays. Results Chondrocytes were treated with interleukin-1β (IL-1β) to mimic OA condition in vitro. CircSCAPER was increased in OA cartilages and IL-1β-induced chondrocytes. Functionally, knockdown of circSCAPER attenuated IL-1β-evoked apoptosis, ECM degradation, inflammation and oxidative stress in vitro. CircSCAPER up-regulation in OA cartilages was discovered to be accompanied by decreased miR-127-5p and increased TLR4. Mechanistically, circSCAPER acted as a sponge for miR-127-5p to positively regulate TLR4 expression in chondrocytes. IL-1β treatment reduced miR-127-5p expression but up-regulated TLR4 expression, re-expression of miR-127-5p suppressed IL-1β-caused chondrocyte injury, which was abolished by TLR4 overexpression. Moreover, miR-127-5p inhibition reversed the protective action of circSCAPER knockdown on chondrocytes under IL-1β treatment. Conclusion CircSCAPER silencing protected against IL-1β-induced apoptosis, ECM degradation, inflammation and oxidative stress in chondrocytes via miR-127-5p/TLR4 axis.

Procyanidin B2 Alleviates Heat-Induced Oxidative Stress through the Nrf2 Pathway in Bovine Mammary Epithelial Cells.

The objective of this study was to investigate the protective effects and potential molecular mechanisms of procyanidin B2 (PB2) in MAC-T (mammary alveolar cells-large T antigen) cells during heat stress (HS). The MAC-T cells were divided into three treatment groups: control (37 °C), HS (42 °C), and PB2 + HS (42 °C). Compared with MAC-T cells that were consistently cultured at 37 °C, acute HS treatment remarkably decreased cell viability, reduced activities of catalase (CAT), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC), and elevated intracellular levels of malondialdehyde (MDA) and reactive oxygen species (ROS). Additionally, nuclear factor erythroid 2-related factor 2 (Nrf2) was activated and translocated to the nucleus, in accompaniment with upregulation of Nrf2, heme oxygenase 1 (HO-1), thioredoxin reductase 1 (Txnrd1), and heat shock protein 70 (HSP70). In parallel, both mRNA transcript and actual protein secretion of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), were increased by heat stress. Pretreatment of MAC-T cells with 0~25 μM PB2 alleviated the decline of cell viability by HS in a dose-dependent fashion and protected cells against HS-induced oxidative stress, as evidenced by significantly improved CAT, SOD, and T-AOC activity, as well as with decreased MDA and ROS generation. Furthermore, PB2 further activated the Nrf2 signaling pathway and reversed the inflammatory response induced by HS. Silencing of Nrf2 by si-Nrf2 transfection not only exacerbated HS-induced cell death and provoked oxidative stress and the inflammatory response, but also greatly abolished the cytoprotective effects under HS of PB2. In summary, PB2 protected MAC-T cells against HS-induced cell death, oxidative stress, and inflammatory response, partially by operating at the Nrf2 signal pathway.

Effects of a polysaccharide extract from Amomum villosum Lour. on gastric mucosal injury and its potential underlying mechanism

AVLP-2, a novel acidic polysaccharide, was isolated and purified from Amomum villosum Lour. The structural characteristics of the polysaccharides were characterized using monosaccharide composition, methylation, FT-IR, and NMR techniques. Results showed that AVLP-2 comprises galactose and glucose monomers, has a molecular weight of 10.488 kDa, and has backbone structures →4)-α-d-GalAp-(1→3,4)-α-d-GalAp-(1→, →4)-α-d-GalAp-(1→6)-α-d-Galp-(1→, and n→6)-α-d-Galp-(1→4)-β-d-Glcp-(1→, with α-d-Galp-(1→ branches. Furthermore, AVLP-2 had a significant protective effect against oxidative stress in alcohol-induced injury and LPS inflammation models GES-1 cells by regulating the levels of ROS and inflammatory factors. In the animal experiments, AVLP-2 improved the oxidative stress status of the gastric mucosa by increasing SOD activity and GSH levels and inhibiting the excessive generation of malondialdehyde in tissues. The levels of MPO, IL-1β, IL-10, and NF-κB p65 were downregulated, while that of TNF-α was upregulated by AVLP-2 treatment, thereby reducing the alcohol-induced inflammation.

Sevoflurane ameliorates LPS-induced inflammatory injury of HK-2 cells through Sirtuin1/NF-κB pathway.

The anesthetic sevoflurane (SEV) has been shown to protect against organ's injury during sepsis. The present study intended to uncover the protective effects of SEV on sepsis-induced acute kidney injury (SI-AKI) and its possible mechanism. Human renal tubular epithelial cell HK-2 was treated with 10 μg/mL lipopolysaccharide (LPS) to construct SI-AKI cell model. LPS-induced HK-2 cells were pretreated with SEV in the absence or presence of EX527, an inhibitor of Sirtuin 1 (SIRT1), after which were the detection of cell viability, lactate dehydrogenase (LDH) release, apoptosis, inflammation, and oxidative stress. Our results demonstrated that LPS caused decreased cell viability, increased LDH release, improved cell apoptosis along with decreased expression of Bcl2 and enhanced expressions of Bax, cleaved PARP and cleaved caspase, enhanced production, and protein expressions of TNF-α, IL-6, and IL-1β, increased generation of reactive oxygen species (ROS) and malondialdehyde (MDA), but contributed to declined activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). LPS inhibited SIRT1 and IκBα expressions but up-regulated p-NF-κB p65 and acetyl-p53 expressions as well. However, SEV pretreatment abolished all above-mentioned effects of LPS on HK-2 cells, while EX527 significantly reversed the effects of SEV. In conclusion, SEV effectively protected HK-2 cells against LPS-induced apoptosis, inflammation, and oxidative stress, and these effects may depend on the increase of SIRT1 expression, thereby inactivating NF-κB signaling.

Regulation of cellular redox homeostasis in Arabidopsis thaliana seedling by atmospheric pressure cold plasma-generated reactive oxygen/nitrogen species

Atmospheric pressure cold plasma (APCP) holds great potential as an efficient, economical and eco-friendly approach for improving crop production. Although APCP-induced plant growth promotion is undisputedly attributed to the reactive oxygen and nitrogen species (RONS), how these RONS regulate the intracellular redox state and plant growth is still largely unknown. This study systematically investigates the regulation mechanism of APCP-generated RONS on intracellular redox homeostasis in Arabidopsis thaliana seedling by measuring the RONS compositions in APCP-treated solutions and intracellular RONS and antioxidants in Arabidopsis seedlings. The results show that APCP exhibited a dual effect (stimulation or inhibition) on Arabidopsis seedling growth dependent on the treatment time. APCP-generated RONS in liquids increased in a time-dependent manner, leading to an increase of conductivity and oxidation reduction potential (ORP) and decrease of pH. APCP caused an enrichment of intracellular RONS and most of them increased with APCP treatment time. Meanwhile, APCP treatment accelerated malondialdehyde (MDA) generation, and the level of intracellular antioxidants were enhanced by low-dose APCP treatment while decreased at high doses. The results of correlation analysis showed that the extracellular RONS produced by APCP were positively correlated with the intracellular RONS and negatively correlated with the antioxidants. These results demonstrate that the improved antioxidant capacity induced by moderate APCP-generated RONS plays an important role in the growth promotion of Arabidopsis seedlings, which may be a promising alternative for fertilizers in agricultural production.

Biochemical and yield response of sugar beet to drought stress and foliar application of vermicompost tea

Vermicompost tea (VCT) possess plant growth regulator properties and could play significant role in mitigating drought stress (DS) effects when applied as fertilizer. Current study was planned to assess the effects of VCT levels (0, 27 and 54 L ha−1) applications on physiological, biochemical and yield of sugar beet when plants were grown under field conditions with DS (100%, 75% and 50% irrigation water requirement (IWR)). The results showed that severe DS reduced root growth and sugar yield by reducing relative water content (RWC) and chlorophyll contents through increased generation of hydrogen peroxide (H2O2) and malondialdehyde (MDA). However, VCT significantly increased root yield by 20% and sugar yield by 33% under 50% IWR. Vermicompost tea could partly alleviate the effects of DS on sugar beet by up-regulation of the antioxidant system and leaf soluble sugars and simultaneous decreasing of H2O2 and MDA.

Betulinic acid attenuates cognitive dysfunction, oxidative stress, and inflammation in a model of T-2 toxin-induced brain damage.

T-2 toxin is a mycotoxin that has harmful effects on the immune system and cognitive function. Betulinic acid (BA) is a plant-derived pentacyclic lupane-type triterpenoid which possesses a wide spectrum of bioactivities. The study was aimed to explore whether BA has a protective effect on cognitive impairment and oxidative stress caused by T-2 toxin. BA was suspended in 1% soluble starch by continuous intragastric administration for 14days, then the brain damage in mice was induced by a single intraperitoneal injection of T-2 toxin (4mg/kg). It was found that BA alleviated the reduction of discrimination index in T-2 toxin-treated mice, and enhanced dopamine (DA), 5-hydroxytryptamine (5-HT), and acetylcholine (ACH) levels of brain neurotransmitter. Meanwhile, BA pretreatment ameliorated oxidative stress through increase of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione (GSH) levels, and inhibition of the generation of reactive oxygen species (ROS) and malondialdehyde (MDA) in the brain of mice exposed to T-2 toxin. Moreover, BA reduced brain hemorrhage and ecchymosis, improved the mitochondrial morphology, enriched the number of organelles, and inhibited cell apoptosis in brain challenged with T-2 toxin. Furthermore, BA inhibited mRNA expression of pro-inflammatory cytokines such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) as well as enhanced mRNA expression of anti-inflammatory cytokine such as IL-10 in the brain of T-2 toxin-triggered mice. Therefore, BA could improve the cognitive function, enhance the antioxidant capacity, and inhibit the secretion of proinflammatory cytokines in brain, thereby playing a preventive and protective role against brain damage caused by T-2 toxin.

Maternal exposure to polystyrene nanoplastics during gestation and lactation induces hepatic and testicular toxicity in male mouse offspring

Nanoplastics have raised considerable concerns since their ubiquity in the environment and potential hazard to health. It has been proven that polystyrene nanoparticles (PS-NPs) can be maternally transferred to the offspring. In this study, mice were exposed gestationally and lactationally to PS-NPs (size 100 nm) at different doses (0.1, 1 and 10 mg/L) to investigate the trans-generational poisonousness. Our data illustrated that maternal PS-NPs exposure in pregnancy and lactation resulted in a decline in birth and postnatal body weight in offspring mice. Furthermore, high-dose PS-NPs reduced liver weight, triggered oxidative stress, caused inflammatory cell infiltration, up-regulated proinflammatory cytokine expression, and disturbed glycometabolism in the liver of male offspring mice. In addition, pre- and postnatal PS-NPs exposure diminished testis weight, disrupted seminiferous epithelium and decreased sperm count in mouse offspring. Moreover, PS-NPs induced testicular oxidative injury, as presented by increased malondialdehyde generation and altered superoxide dismutase and catalase activities in the testis of offspring mice. These findings declared that maternal exposure to PS-NPs in pregnancy and lactation can cause hepatic and testicular toxicity in male mouse pups, which put forward new understanding into the detrimental effects of nanoplastics on mammalian offspring.

Tanshinone IIA protected against lipopolysaccharide-induced brain injury through the protective effect of the blood-brain barrier and the suppression of oxidant stress and inflammatory response.

Brain microvascular endothelial cells are essential components of the blood-brain barrier (BBB) that acts as a selective physical barrier and plays protective roles in maintaining brain homeostasis. Tanshinone IIA (Tan IIA), isolated from Salvia miltiorrhiza Bunge, exhibited healthy effects such as antioxidant effects, anti-inflammatory effects, and cardiovascular protective effects. Here, we tried to investigate the positive effect and the potential mechanism of Tan IIA on the lipopolysaccharide (LPS)-induced brain injury in mice and brain microvascular endothelial cells in vitro. In vivo, Tan IIA inhibited the brain injury, and the enhancement of blood-brain barrier permeability in the LPS-induced brain injury in mice. Moreover, Tan IIA suppressed inflammatory response and oxidant response in LPS-treated mice evidenced by low levels of serum TNF-α and IL-1β, high superoxide dismutase (SOD) activity and low malondialdehyde (MDA) in the brain. In vitro, Tan IIA suppressed the generation of reactive oxygen species (ROS) and MDA, and promoted SOD activity in LPS-stimulated brain microvascular endothelial cells. Moreover, Tan IIA promoted the expression of Claudin5, ZO-1, Nrf2, HO-1 and NQO1 in LPS-stimulated brain microvascular endothelial cells. In conclusion, Tan IIA protected against the LPS-induced brain injury via the suppression of oxidant stress and inflammatory response and protective effect of the BBB through activating Nrf2 signaling pathways and rescue of the tight junction proteins in microvascular endothelial cells, supporting the application of Tan IIA and Salvia miltiorrhiza Bunge as food supplements for the treatment of brain disease.

Оксидантно-антиоксидантна система крові при експериментальній емфіземі легень

Abstract. Bronchial asthma ( BA) is one of the most common diseases of the human respiratory organs and occupies one of the leading places both in the terms of the prevalence and the severity of manifestations. With a long duration of BA, concomitant smoking, the irreversible bronchial obstruction formation, some patients develop pulmonary emphysema. The pathogenesis of pulmonary emphysema is multifactorial and consists in the mechanisms of oxidative stress, imbalance of the protease/antiprotease system, activation of inflammatory cells and production of inflammatory mediators. Oxidative stress is one of the main processes in the formation of pulmonary emphysema, but its exact mechanisms, which could be targeted by pathogenetic therapy, have not yet been studied. The study of pulmonary emphysema pathogenesis in patients is often complicated due to the influence of a large number of random combinations of the various factors. One way to avoid such influence is experiment. The aim is to study the nature of changes in the oxidant-antioxidant system of the blood in the experimental pulmonary emphysema. Methods. Experimental studies were carried out on 24 mature, outbred white rats weighing 180-200 g, which were kept on a standard vivarium diet. To assess the intensity of lipid peroxidation in the animal blood, the content of its final product, malondialdehyde, was determined. The the antioxidant system activity was assessed by the content of ceruloplasmin and catalase activity in the blood. Results. The results of the conducted studies indicate a significant increase in the level of malondialdehyde in the blood in conditions of experimental pulmonary emphysema by 30 %. At the same time, a decrease in the content of ceruloplasmin in the blood by 20 % and catalase activity by 29 % was revealed. Conclusions. In experimental pulmonary emphysema, enhanced generation of malondialdehyde leads to the development of oxidative stress and intoxication, disruption of the functions of the antioxidant and antiperoxide defense systems of the body, as evidenced by the significant decrease in the level of ceruloplasmin and catalase activity in the blood.

Chemical inducer of regucalcin attenuates lipopolysaccharide-induced inflammatory responses in pancreatic MIN6 β-cells and RAW264.7 macrophages.

We previously isolated derrisfolin A, a novel rotenoid derivative, from the stems of Derris trifoliata Lour. (Leguminosae). Here, we report that derrisfolin A induces the expression of endogenous regucalcin (RGN) protein in both pancreatic MIN6 β‐cells and RAW264.7 macrophages. Induction of RGN expression by derrisfolin A or retrovirus‐mediated gene transfer in MIN6 cells and RAW264.7 macrophages significantly decreased lipopolysaccharide (LPS)‐induced mRNA expression of Nos2, Il1b, and Tnf via nuclear factor‐κB activation; reduced LPS‐induced apoptosis in MIN6 cells, accompanied by decreased production of nitric oxide, interleukin‐1β, and tumor necrosis factor‐α; and attenuated generation of LPS‐induced reactive oxygen species, malondialdehyde, and 3‐nitrotyrosine in MIN6 cells. Additionally, in co‐cultures of MIN6 cells with RAW264.7 macrophages in the presence of LPS, induction of RGN expression by derrisfolin A or retrovirus‐mediated gene transfer in RAW264.7 macrophages attenuated apoptosis and oxidative/nitrosative stress in MIN6 cells. These results suggest that the induction of RGN expression in MIN6 cells was effective in suppressing LPS‐induced inflammatory cytotoxicity and that in co‐culture conditions, the induction of RGN expression in RAW264.7 macrophages blocked LPS‐induced paracrine effects of RAW264.7 macrophages on inflammatory cytotoxicity in MIN6 cells. Our findings suggest that derrisfolin A, a chemical inducer of RGN, might be useful for developing a new drug against macrophage‐associated β‐cell inflammation in type 2 diabetes.

Oleuropein Enhances Stress Resistance and Extends Lifespan via Insulin/IGF-1 and SKN-1/Nrf2 Signaling Pathway in Caenorhabditis elegans.

Oleuropein (OLE) is a secoiridoid glycoside that mainly exists in olives with multifaceted health benefits. The present study aimed to investigate the stress resistance and lifespan extension effects of OLE in Caenorhabditis elegans. The results showed that OLE could significantly prolong the lifespan of C. elegans by 22.29%. Treatment with OLE also significantly increased the survival rates of worms against lethal heat shock and oxidative stress. Meanwhile, OLE supplementation increased the expression and activity of antioxidant enzymes and suppressed the generation of malondialdehyde in nematodes. In addition, the results from mutants implied that OLE might mediate longevity and stress resistance via DAF-16/FoxO, which played a vital role in the insulin/IGF-1 signaling (IIS) pathway. To further identify the molecular targets of OLE, mRNA level and loss-of-function mutants of IIS-associated genes were investigated. The data revealed that OLE activated IIS by down-regulating the upstream components, daf-2 and age-1. Furthermore, another stress response and longevity pathway in parallel to DAF-16, SKN-1/Nrf2, was also shown to involve in OLE-induced beneficial effects. Collectively, these results provide the theoretical basis that OLE could enhance the stress resistance and increase the lifespan of C. elegans through the IIS and SKN-1/Nrf2 signaling pathways.

In vitro genotoxicity of dibutyl phthalate on A549 lung cells at air-liquid interface in exposure concentrations relevant at workplaces.

The ubiquitous use of phthalates in various materials and the knowledge about their potential adverse effects is of great concern for human health. Several studies have uncovered their role in carcinogenic events and suggest various phthalate-associated adverse health effects that include pulmonary diseases. However, only limited information on pulmonary toxicity is available considering inhalation of phthalates as the route of exposure. While in vitro studies are often based on submerged exposures, this study aimed to expose A549 alveolar epithelial cells at the air-liquid interface (ALI) to unravel the genotoxic and oxidative stress-inducing potential of dibutyl phthalate (DBP) with concentrations relevant at occupational settings. Within this scope, a computer modeling approach calculating alveolar deposition of DBP particles in the human lung was used to define in vitro ALI exposure conditions comparable to potential occupational DBP exposures. The deposited mass of DBP ranged from 0.03 to 20 ng/cm2 , which was comparable to results of a human lung particle deposition model using an 8h workplace threshold limit value of 580 μg/m3 proposed by the Scientific Committee on Occupational Exposure Limits for the European Union. Comet and Micronucleus assay revealed that DBP induced genotoxicity at DNA and chromosome level in sub-cytotoxic conditions. Since genomic instability was accompanied by increased generation of the lipid peroxidation marker malondialdehyde, oxidative stress might play an important role in phthalate-induced genotoxicity. The results highlight the importance of adapting in vitro studies to exposure scenarios relevant at occupational settings and reconsidering occupational exposure limits for DBP.