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Background: Diabetic complications-coronary atherosclerosis is closely related to the increased reactive oxygen species (ROS) induced by hyperglycemia. ROS are reported to induce the abnormal proliferation of vascular smooth muscle cells (VSMCs) under high glucose conditions. Leaf and seed extracts from Moringa oleifera are found to exhibit antioxidant activity. However, few studies are evaluating the antioxidant activities of chemical compounds isolated from the M. oleifera especially in cardiovascular field., Purpose: The aim of this study is to explore the antioxidative effect during hyperglycemia of niazirin from M. oleifera., Study Design: A cell model was applied., Methods: After the taking the in vitro antioxidant experiment including ferric reducing antioxidant power (FRAP), 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) assay and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Cell viability was carried out using high glucose-induced VSMCs model. ROS production was tested by 2',7'-dichlorofluorescein diacetate (DCF-DA) assay. The protein kinase C zeta (PKCζ) and NADPH oxidase 4 (Nox 4) expression in vitro and in vivo were measured by western blot analysis., Results: Niazirin showed good free radical scavenging activity. Niazirin significantly attenuated the proliferation of high glucose-induced VSMCs. Furthermore, it could decrease the ROS and malondialdehyde (MDA) productions, while increased total antioxidant capacity (T-AOC), superoxide dismutase (SOD) as well as glutathione peroxidase (GPx) levels in high glucose-induced VSMCs and streptozotocin-induced mice. In addition, niazirin could eliminate the high glucose-induced PKCζ activation, indicated by Thr410 phosphorylation and inhibition of the Nox4 protein expression in vitro and in vivo., Conclusion: Niazirin from M. oleifera exhibited notably antioxidant activities and could be utilized as a potential natural antioxidant in preventing diabetic atherosclerosis., (Copyright © 2019. Published by Elsevier GmbH.)

This study explores the antioxidative effect of a specific wheat germ-derived peptide on high glucose-induced oxidative stress in vascular smooth muscle cells (VSMCs) and the underlying mechanisms. The peptide ADWGGPLPH was identified by LC-MS/MS. The effects of this peptide on the production of ROS and the expression of oxidative stress signaling proteins in VSMCs were determined. STZ-induced mice were utilized to confirm the anti-oxidative and anti-diabetic cardiovascular disease effects of this peptide in vivo. The results showed that ADWGGPLPH significantly prevented high glucose-induced cell proliferation, decreased intracellular ROS generation, stimulated AMPK activity, inhibited the PKCζ, AKT and Erk1/2 phosphorylation, and suppressed NOX4 protein expression. In addition, ADWGGPLPH enhanced the antioxidant abilities and attenuated inflammatory cytokine generation in STZ-induced diabetic mice. Therefore, ADWGGPLPH prevents high glucose-induced oxidative stress in VSMCs by modulating the PKCζ/AMPK/NOX4 pathway.

Underground drinking water is commonly contaminated with arsenite (As) and fluoride (F) associated with chronic kidney diseases in humans; however, the combined renal toxicity of these pollutants and the underlying mechanisms are still unclear. The aim of the present study was to investigate the interaction between As and F regarding toxic effects on the kidney of rat offspring exposed to pollutants during prenatal and postnatal development. Pregnant rats were randomly divided into four groups that received NaAsO 2 (50 mg/L), NaF (100 mg/L), NaAsO 2 (50 mg/L) and NaF (100 mg/L) in drinking water, or clean water, respectively, during gestation and lactation. After weaning, six male pups were randomly selected from each group and continued on the same treatment as their mothers for up to three months. The results revealed that subchronic exposure to high-dose As and/or F decreased the organ coefficient of the kidneys and disrupted kidney ultrastructure, moreover inhibited the activity of antioxidant enzymes and increased the generation of malondialdehyde in the kidney. As exposure alone or combined with F led to an upregulation of nuclear factor erythroid 2-related factor-2 (Nrf2) and its regulatory targets (Ho-1, Gclc, and Nqo1), whereas the effect of F alone was not significant. These results suggest that the renal toxicity of As and F is associated with the induction of mitochondrial damage and oxidative stress, and alters the expression of Nrf2 and its regulatory targets. Furthermore, variance analysis results showed that an interaction between As and F in the toxicity process., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Our study demonstrates that occupational exposure to nano-CaCO3 could lead to the poor pulmonary function observed among occupational workers. Oxidative stress participate in mechanisms of lung injury induced by nano-CaCO3. Especially, the results can provide information for proposing occupational strategies for reducing the occupational hazards. Objective: The aim of the study is to investigate whether nano–calcium carbonate (nano-CaCO3) occupational exposure could induce adverse health effects in workers. Methods: A cross-sectional study was conducted in a nano-CaCO3 manufacturing plant in China. Then, we have studied the dynamic distribution of nano-CaCO3 in nude mice and examined the oxidative damage biomarkers of subchronic administrated nano-CaCO3 on Sprague-Dawley rats. Results: The forced vital capacity (%) and the ratio of FEV1 to FVC is the rate of one second of workers were significantly decreased than unexposed individuals. Dynamic imaging in mice of fluorescence labeled nano-CaCO3 showed relatively high uptake and slow washout in lung. Similar to population data, the decline in serum glutathione level and elevation in serum MDA were observed in nano-CaCO3–infected Sprague-Dawley rats. Conclusions: We found that nano-CaCO3 exposure may result in the poor pulmonary function in workers and lead to the changes of oxidative stress indexes. [ABSTRACT FROM AUTHOR]

Background: Astaxanthin is a red lipophilic carotenoid that is often undetectable in human plasma due to the limited supply in typical Western diets. Despite its presence at lower than detectable concentrations, previous clinical feeding studies have reported that astaxanthin exhibits potent antioxidant properties.Objective: We examined astaxanthin accumulation and its effects on gut microbiota, inflammation, and whole-body metabolic homeostasis in wild-type C57BL/6 J (WT) and β-carotene oxygenase 2 (BCO2) knockout (KO) mice.Methods: Six-wk-old male and female BCO2 KO and WT mice were provided with either nonpurified AIN93M (e.g., control diet) or the control diet supplemented with 0.04% astaxanthin (wt/wt) ad libitum for 8 wk. Whole-body energy expenditure was measured by indirect calorimetry. Feces were collected from individual mice for short-chain fatty acid assessment. Hepatic astaxanthin concentrations and liver metabolic markers, cecal gut microbiota profiling, inflammation markers in colonic lamina propria, and plasma samples were assessed. Data were analyzed by 3-way ANOVA followed by Tukey's post hoc analysis.Results: BCO2 KO but not WT mice fed astaxanthin had ∼10-fold more of this compound in liver than controls (P < 0.05). In terms of the microbiota composition, deletion of BCO2 was associated with a significantly increased abundance of Mucispirillum schaedleri in mice regardless of gender. In addition to more liver astaxanthin in male KO compared with WT mice fed astaxanthin, the abundance of gut Akkermansia muciniphila was 385% greater, plasma glucagon-like peptide 1 was 27% greater, plasma glucagon and IL-1β were 53% and 30% lower, respectively, and colon NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation was 23% lower (all P < 0.05) in male KO mice than the WT mice.Conclusions: Astaxanthin affects the gut microbiota composition in both genders, but the association with reductions in local and systemic inflammation, oxidative stress, and improvement of metabolic homeostasis only occurs in male mice. [ABSTRACT FROM AUTHOR]

β,β-Carotene-9',10'-oxygenase 2 (BCO2) is a protein localized to the inner membrane of mitochondria. It was initially discovered as an enzyme that catalyzes the asymmetric cleavage of carotenoids. Systemic depletion of BCO2 causes increased food intake and impaired hepatic lipid metabolism in mice. The aim of this current study was to determine the extent to which BCO2 exerts its role in hypothalamic nutrient metabolism and feeding behavior through remodeling the hypothalamic metabolome in mice. Male BCO2 knockout (KO) and the isogenic wild-type 129S6 (WT) mice at 6 weeks of age were used for metabolic and cytokine and hypothalamic metabolomics and biochemical analysis. Compared to the WT, BCO2 KO mice exhibited widespread disruptions in metabolism and metabolite homeostasis, an increase in fasting blood glucose, a decrease in circulating glucagon and leptin, an elevation of plasma interleukin 1 beta and tumor necrosis factor alpha, and impaired AMP-activated protein kinase signaling. The global hypothalamic metabolomic results revealed that depletion of BCO2 resulted in striking metabolic changes, including suppression of long-chain fatty acids transport into mitochondria, inhibition of the metabolism of dipeptides and sulfur-containing amino acids, and stimulation of local oxidative stress and inflammation in the hypothalamus of BCO2 KO mice. These findings suggest that BCO2 regulates hypothalamic mitochondrial function, nutrient metabolism, and local oxidative stress and inflammation. Complex interplay between the hormone signaling and impaired lipid and glucose metabolism could account for initiation of oxidative stress, inflammation and eventual metabolic disorders in BCO2 KO mice. [ABSTRACT FROM AUTHOR]

Studies have shown that PM 2.5 exposure can induce neuronal apoptosis and neurobehavioral changes in animal experiments due partly to the mitochondria-mediated oxidative damage. How does it affect the mitochondrial energy metabolism as well as the neuronal damage, however, remain unclear. This study aimed to investigate the molecular processes of energy metabolism and oxidative damage induced by ambient PM 2.5 exposure in SH-SY5Y cells. SH-SY5Y cells were treated with PM 2.5 to establish a cytotoxicity model. A Seahorse Extracellular Flux Analyzer (XFp) was performed to evaluate the cellular mitochondrial respiratory and glycolysis after exposure to PM 2.5. The dose- and time-dependent effects of PM 2.5 on oxidative damage and apoptosis were analyzed. To further explore the relationship among oxidative damage, energy metabolism and apoptosis, SH-SY5Y cells were co-cultured with BHA and PM 2.5 for 24 h. The results demonstrated that the basic respiration and ATP production, the typical index of mitochondrial respiration as well as glycolysis, significantly reduced in SH-SY5Y cells with dose and time dependent. At the same time, the PM 2.5 could significantly decrease the cell viability and Mn-SOD activity, and increase the ROS levels and apoptosis rate as the escalation of dose and the extension of time. Importantly, the application of BHA could synchronously recover the PM 2.5 induced cell energy metabolism disorder, oxidative damage, and apoptosis. It seems that the abnormal cellular energy metabolism may be caused by oxidative damage following fine particles exposure, and further led to apoptosis. • The alteration of the molecular processes of energy metabolism induced by ambient PM 2.5 is proposed. • Cellular mitochondrial respiration is more sensitive to PM 2.5 treatment, while glycolysis only shows damage at high doses and prolonged treatment time. • BHA significantly recovered the effects of PM 2.5 on mitochondrial respiration. [ABSTRACT FROM AUTHOR]

Low-grade inflammation is a critical pathological factor contributing to the development of metabolic disorders. β-carotene oxygenase 2 (BCO2) was initially identified as an enzyme catalyzing carotenoids in the inner mitochondrial membrane. Mutations in BCO2 are associated with inflammation and metabolic disorders in humans, yet the underlying mechanisms remain unknown. Here, we used loss-of-function approaches in mice and cell culture models to investigate the role of BCO2 in inflammation and metabolic dysfunction. We demonstrated decreases in BCO2 mRNA and protein levels and suppression of mitochondrial respiratory complex I proteins and mitochondrial superoxide dismutase levels in the liver of type 2 diabetic human subjects. Deficiency of BCO2 caused disruption of assembly of the mitochondrial respiratory supercomplexes, such as supercomplex III 2 +IV in mice, and overproduction of superoxide radicals in primary mouse embryonic fibroblasts. Further, deficiency of BCO2 increased protein carbonylation and populations of natural killer cells and M1 macrophages, and decreased populations of T cells, including CD4+ and/or CD8+ in the bone marrow and white adipose tissues. Elevation of plasma inflammatory cytokines and adipose tissue hypertrophy and inflammation were also characterized in BCO2 deficient mice. Moreover, BCO2 deficient mice were more susceptible to high-fat diet-induced obesity and hyperglycemia. Double knockout of BCO2 and leptin receptor genes caused a significantly greater elevation of the fasting blood glucose level in mice at 4 weeks of age, compared to the age- and sex-matched leptin receptor knockout. Finally, administration of Mito-TEMPO, a mitochondrial specific antioxidant attenuated systemic low-grade inflammation induced by BCO2 deficiency. Collectively, these findings suggest that BCO2 is essential for mitochondrial respiration and metabolic homeostasis in mammals. Loss or decreased expression of BCO2 leads to mitochondrial oxidative stress, low-grade inflammation, and the subsequent development of metabolic disorders. Image 1 • BCO2 mRNA and protein levels are decreased in liver of type 2 diabetic human subjects. • BCO2 deficient mice are more susceptible to diet-induced obesity and type 2 diabetes. • Deficiency of BCO2 impairs mitochondrial respiratory supercomplex assembly. • Deficiency of BCO2 stimulates superoxide overproduction in mitochondria. • Mito-TEMPO attenuates BCO2 deficiency-induced low-grade inflammation in mice. [ABSTRACT FROM AUTHOR]

Phenethyl isothiocyanate (PEITC), a kind of isothiocyanate available in cruciferous vegetables, exhibits inhibitory effects on cancers. PEITC has been extensively recorded for its effect on regulation of redox status in cancer cells. Our previous studies revealed that PEITC induced ROS-dependent cell death in osteosarcoma. Mitochondria are the main sites for ROS generation and play significant role in deciding cell fate. To dissect the mechanism of PEITC's action on osteosarcoma cells, we detected the changes on mitochondrial network, function and metabolism in K7M2 and 143B cells. Here, PEITC induced cytosolic, lipid and mitochondrial ROS production in osteosarcoma cells. It changed mitochondrial morphology from elongated to punctate network and decreased mitochondrial mass. Meantime, PEITC increased mitochondrial transmembrane potential in short time, decreased it with time prolonged, and later collapsed it in K7M2 cells, and reduced it in 143B cells. PEITC inhibited proliferation potential of osteosarcoma cells with damage on mitochondrial respiratory chain complexes. Further, PEITC-treated osteosarcoma cells experienced a sudden increase in ATP level, and later its content was decreased. Moreover, PEITC downregulated the expressions of mitochondrial respiratory chain complexes including COX IV, UQCR, SDHA and NDUFA9 in 143B cells and COX IV in K7M2 cells. At last, by using ρ0 cells derived from K7M2 and 143B cells, we found that osteosarcoma cells that depleted mtDNA were less sensitive to PEITC-induced changes on cellular morphology, cytoskeleton filament, mitochondrial transmembrane potential and ROS generation. In conclusion, our study demonstrated that mitochondria may play important role in PEITC-induced oxidative cell death in osteosarcoma cells. [Display omitted] • PEITC-induced alteration of lipid and mitochondrial ROS was consistent with changes in cytosolic ROS in PEITC-treated K7M2 and 143B cells over time. • PEITC changed mitochondrial morphology from elongated to punctate network and decreased mitochondrial mass in K7M2 and 143B cells. • PEITC increased mitochondrial membrane potential in short treatment time, then decreased it with time prolonged, and later collapsed it in K7M2 cells, and reduced it in 143B cells. • PEITC altered ATP metabolism and affected the expression of mitochondrial proteins in K7M2 and 143B cells. • ρ0 K7M2 cells and ρ0 143B cells were much less sensitive to PEITC-induced changes on cellular morphology, filament, mitochondrial transmembrane potential and ROS generation. [ABSTRACT FROM AUTHOR]

In this work, a novel isophorone-derived fluorescent probe, ISOP-SFT , was developed for the detection of sulfite, and, for the first time, it was applied into monitoring the state of hybridoma cells. ISOP-SFT could exhibit a red-emission response to sulfite with the excitation at 455 nm. It also indicated practical advantages such as wide pH tolerance within 6.0–9.0 and high storage steadiness within at least one week. The linear range was relatively long (0–20 Eq) and reliable (Pearson's correlation coefficient: 0.9989), while Limit of Detection was determined as 0.0095 Eq (95 nM). For the selectivity, ISOP-SFT could distinguish sulfite from other analytes, and the response of ISOP-SFT towards sulfite was not seriously interfered in co-existence system. With low cytotoxicity, ISOP-SFT achieved monitoring both the exogenous and endogenous sulfite in living MCF-7 cells. As a novel attempt, ISOP-SFT was applied into monitoring the state of hybridoma cells, and associated with the quality control of producing antibodies. The result preliminarily inferred the positive correlation between the production efficiency of antibodies in hybridoma cells and the intracellular sulfite level, including the conditions of serum starvation, oxidative stress, severe hypoxia and endogenous induction. We hope that the information in this work could lead to new applications of fluorescent probes in biological industry in future. A novel isophorone-derived fluorescent probe, ISOP-SFT , was developed for the detection of sulfite, and, for the first time, it was applied into monitoring the state of hybridoma cells. It also indicated practical advantages such as red emission, wide pH tolerance and high storage steadiness. The linear range was relatively long and reliable, while Limit of Detection was determined as 0.0095 Eq (95 nM). ISOP-SFT could distinguish sulfite from other analytes with on interference in co-existence system. With low cytotoxicity, ISOP-SFT achieved monitoring both the exogenous and endogenous sulfite in living MCF-7 cells. As a novel attempt, ISOP-SFT was applied into monitoring the state of hybridoma cells, and associated with the quality control of producing antibodies. [Display omitted] • For the first time, applying a novel fluorescent probe, ISOP-SFT , into monitoring the state of hybridoma cells. • Introducing advantages including red emission, wide pH tolerance, high storage steadiness, high sensitivity and selectivity. • Revealing the positive correlation between the production efficiency of antibodies and the intracellular sulfite level. • Investigating the conditions of serum starvation, oxidative stress, severe hypoxia and endogenous induction. [ABSTRACT FROM AUTHOR]