- Design and Development of Novel 1,3,5-Triazine-Procaine Derivatives as Protective Agent against Myocardial Ischemia/Reperfusion Injury via Inhibitor of Nuclear Factor-κB. [Journal Article]
- PPharmacology 2019 Jun 18; :1-13
- The aim of the present study was to determine the protective effect of novel 1,3,5-triazine-procaine derivatives against myocardial ischemia/reperfusion (I/R) injury. Initially, the experiment has be…
The aim of the present study was to determine the protective effect of novel 1,3,5-triazine-procaine derivatives against myocardial ischemia/reperfusion (I/R) injury. Initially, the experiment has been started by the synthesis of procaine, which later got substituted with diverse 1,3,5-triazine derivatives to furnish the final compounds. The target compounds were tested for nuclear factor-κB (NF-κB) inhibitory activity in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The antioxidant activity of most potent compound 9i was investigated using hydroxyl radical, DPPH, and superoxide anion scavenging assay. Compound 9i was further evaluated for protective effect against myocardial I/R injury on the basis numerous parameters, for example, hemodynamic parameters (left ventricular developed pressure [LVDP], ±dp/dtmax, coronary flow [CF], and heart rate [HR]), myocardial enzymes (creatine kinase and lactate dehydrogenase), thiobarbituric acid reactive substance (TBARS), oxidative stress (super oxide dismutase [SOD], catalase [CAT], glutathione [GSH], and glutathione peroxidise [GPx]), histopathology, western blots analysis for B-cell lymphoma 2 (Bcl-2), Bcl-2-associated x protein (Bax), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), and NF-κB in cardiac tissues. Compounds showed significant inhibition of NF-ĸB transcriptional activity in LPS-stimulated RAW264.7 cells, revealing compound 9i as a most potent derivative. In vitro results showed efficient reduction of reduced hydroxyl radical, DPPH, and superoxide anion by 9i. The level LVDP, ±dp/dtmax, CF, HR, TBARS, SOD, CAT, GSH, GPx, and damaged cardiac histopathology were completely restored to normal in 9i-treated group, as compared to I/R group. In western blot analysis, the expression of Bax, LOX-1, and NF-ĸB was found to be decreased, while the level of Bcl-2 was found to be increased in 9i-treated group. The procaine-1,3,5-triazine derivatives showed significant cardioprotective action via inhibition of NF-ĸB.
- Responses of catalase and superoxide dismutase to low-dose quantum dots on molecular and cellular levels. [Journal Article]
- EEEcotoxicol Environ Saf 2019 Jun 15; 181:388-394
- With the wider application of cadmium-containing quantum dots (Cd-QDs) in biomedical fields, it is easier for people to be exposed. Studies have suggested that Cd-QDs could release cadmium ion and in…
With the wider application of cadmium-containing quantum dots (Cd-QDs) in biomedical fields, it is easier for people to be exposed. Studies have suggested that Cd-QDs could release cadmium ion and induce oxidative effects due to the disruption of redox equilibrium. Antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD), play an important role in organisms to resist the negative impact of exogenous substances. Molecular mechanisms of antioxidant enzymes with Cd-QDs remain unclear, however. In this study, structural and functional changes of CAT and SOD have been investigated under low dose Cd-QDs exposure. Cell viability, malondialdehyde (MDA) level, CAT and SOD activities were influenced by Cd-QDs in hepatocytes of mice. To further investigate the responses of CAT and SOD to Cd-QDs, multiple spectroscopic, calorimetric and activity measurements were carried out. Similar interaction patterns were observed that result in interaction force, structural and functional changes: Cd-QDs combine with CAT and SOD through hydrophobic forces; Intrinsic fluorescence of proteins was statically quenched by Cd-QDs and new complexes were formed; Also, the skeleton and secondary structure (with α-helix decrease) of CAT and SOD was influenced. Taken together, we suggest that Cd-QDs chosen in this study induce oxidative stress effects to hepatocytes but have not caused serious oxidative stress damage at concentrations below 10 μg/mL. MPA-CdSe/ZnS QDs caused the lowest level of oxidative stress which is associated with the induction of antioxidant proteins. This paper presents responses of CAT and SOD to low-dose Cd-QDs, and provides a reference for evaluating health damages caused by Cd-QDs.
- Toxic effects of 1-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-4-butanal on the maturation and subsequent development of murine oocyte. [Journal Article]
- EEEcotoxicol Environ Saf 2019 Jun 15; 181:370-380
- Cigarette smoke can cause follicle destruction and oocyte dysfunction and increase the risks of spontaneous abortion, stillbirth, and tubal ectopic pregnancy, affecting female reproductive health. Th…
Cigarette smoke can cause follicle destruction and oocyte dysfunction and increase the risks of spontaneous abortion, stillbirth, and tubal ectopic pregnancy, affecting female reproductive health. Third-hand smoke (THS) is residual tobacco smoke existing in the environment long after cigarettes are extinguished, which can react with other compounds in the environment to produce secondary pollutants. However, the effects of THS on the female reproductive system, particularly the maturation of the oocyte, remain unclear. 1-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-4-butanal (NNA), a component of THS, is a logical biomarker of THS exposure. Thus, this study aims to investigate the toxic effects of NNA on the maturation of murine oocytes and subsequent developmental competence. Herein, murine oocytes were exposed to 0 (control group), 0.1, 1.0, 10, and 50 μM NNA for 24 h. Our results showed that NNA exposure reduced the polar body extrusion rate by causing 8-oxo-deoxyguanosine (8-OHdG) to increase and disrupting the meiotic spindle morphology by inhibiting ERK1/2 activation during in vitro maturation. Additionally, NNA exposure resulted in cleavage and blastocyst rate reduction by altering DNA and histone methylations by reducing 5 mC and H3K4me2 levels and by inducing apoptosis caused by mitochondrial dysfunction and reactive oxygen species accumulation, as shown by the increased superoxide dismutase mRNA level and by the decreased Bcl-x mRNA level. Collectively, our results demonstrate that NNA exposure reduces the maturation and developmental capability of murine oocytes by increasing the risk of DNA damage and abnormal spindle morphology, altering epigenetic modifications, and inducing apoptosis, suggesting the toxic effect of NNA on mammalian productive health.
- Antioxidant enzyme cycling over reproductive lunar cycles in Pocillopora damicornis. [Journal Article]
- PPeerJ 2019; 7:e7020
- The impacts of continued degradation of watersheds on coastal coral reefs world-wide is alarming, and action addressing anthropogenic stressors and subsequent rehabilitation of watersheds and adjacen…
The impacts of continued degradation of watersheds on coastal coral reefs world-wide is alarming, and action addressing anthropogenic stressors and subsequent rehabilitation of watersheds and adjacent reefs is an urgent priority. The aim of this study is to develop and improve the use of antioxidant enzymes as bioindicators of stress in coral species. In order to fully develop such tools, it is necessary to first understand baseline cycling of these enzymes within coral tissues. Due to inherent links between reproduction and oxidative stress, these aims may be facilitated by sampling coral tissues over reproductively-linked lunar cycles to determine variations from baseline. By developing a greater understanding of biochemical markers of stress in corals, specifically antioxidant defense enzymes catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), and superoxide dismutase (SOD) in Hawaiian Pocillopora damicornis, we have provided molecular tools that identify thresholds of stress on coral reefs. Our results suggest that the coral reproductive state is a significant factor affecting the activity of antioxidant enzymes. Specifically, CAT and GR display maximum activity during peak reproductive state. Whereas significant maximal Se-independent GPx and SOD activity was measured during off-peak reproductive cycles. Such insight into the cyclical variation of the activity of these enzymes should be applied towards differentiating the influence of natural biological activity cycling in diagnostic tests identifying the effects of different physical environmental factors and chemical pollutants on coral health. Through the development and application of these molecular biomarkers of stress, we look to improve our ability to identify problems at the sub-lethal level, when action can be taken to mitigate a/biotic impacts.
- Chronic Alcohol Exposure Induced Neuroapoptosis: Diminishing Effect of Ethyl Acetate Fraction from Aralia elata. [Journal Article]
- OMOxid Med Cell Longev 2019; 2019:7849876
- An ethyl acetate fraction from Aralia elata (AEEF) was investigated to confirm its neuronal cell protective effect on ethanol-induced cytotoxicity in MC-IXC cells and its ameliorating effect on neuro…
An ethyl acetate fraction from Aralia elata (AEEF) was investigated to confirm its neuronal cell protective effect on ethanol-induced cytotoxicity in MC-IXC cells and its ameliorating effect on neurodegeneration in chronic alcohol-induced mice. The neuroprotective effect was examined by methylthiazolyldiphenyl-tetrazolium bromide (MTT) and 2',7'-dichlorodihydrofluorescein diacetate (DCF-DA) assays. As a result, AEEF reduced alcohol-induced cytotoxicity and oxidative stress. To evaluate the improvement of learning, memory ability, and spatial cognition, Y-maze, passive avoidance, and Morris water maze tests were conducted. The AEEF groups showed an alleviation of the decrease in cognitive function in alcohol-treated mice. Then, malondialdehyde (MDA) levels and the superoxide dismutase (SOD) content were measured to evaluate the antioxidant effect of AEEF in the brain tissue. Treatment with AEEF showed a considerable ameliorating effect on biomarkers such as SOD and MDA content in alcohol-induced mice. To assess the cerebral cholinergic system involved in neuronal signaling, acetylcholinesterase (AChE) activity and acetylcholine (ACh) content were measured. The AEEF groups showed increased ACh levels and decreased AChE activities. In addition, AEEF prevented alcohol-induced neuronal apoptosis via improvement of mitochondrial activity, including reactive oxygen species levels, mitochondrial membrane potential, and adenosine triphosphate content. AEEF inhibited apoptotic signals by regulating phosphorylated c-Jun N-terminal kinases (p-JNK), phosphorylated protein kinase B (p-Akt), Bcl-2-associated X protein (BAX), and phosphorylated Tau (p-Tau). Finally, the bioactive compounds of AEEF were identified as caffeoylquinic acid (CQA), 3,5-dicaffeoylquinic acid (3,5-diCQA), and chikusetsusaponin IVa using the UPLC-Q-TOF-MS system.
- Preliminary Findings of Platelet-Rich Plasma-Induced Ameliorative Effect on Polycystic Ovarian Syndrome. [Journal Article]
- CJCell J 2019; 21(3):243-252
- CONCLUSIONS: PRP is able to regulate hormonal interaction, improve the ovarian antioxidant potential as well as folliculogenesis and its auto-location could be considered as a novel method to prevent/ameliorate PCOS-induced pathogenesis.
- Metformin with propofol enhances the scavenging ability of free radicals and inhibits lipid peroxidation in mice. [Journal Article]
- EREur Rev Med Pharmacol Sci 2019; 23(11):4980-4987
- CONCLUSIONS: Metformin improves the anesthetic effect of a single dose or continuous intraperitoneal injection of propofol in mice. The compatibility of a certain dose of metformin with propofol can enhance the scavenging ability of free radicals and their metabolites. Furthermore, this inhibits lipid peroxidation in mice via NF-κB inhibition and Nrf2 activation.
- Rutin attenuates vancomycin-induced renal tubular cell apoptosis via suppression of apoptosis, mitochondrial dysfunction, and oxidative stress. [Journal Article]
- PRPhytother Res 2019 Jun 17
- Vancomycin is a glycopeptide antibiotic widely used to treat infections caused by methicillin-resistant Staphylococcus aureus. However, nephrotoxicity is a major adverse side effect, and the developm…
Vancomycin is a glycopeptide antibiotic widely used to treat infections caused by methicillin-resistant Staphylococcus aureus. However, nephrotoxicity is a major adverse side effect, and the development of effective nephroprotective agents remains a priority in antimicrobial chemotherapy. In this study, we investigated the cell protective effects of the flavonol glycoside rutin against vancomycin-induced toxicity. Vancomycin added to porcine renal tubular LLC-PK1 cells caused an increase of production of intracellular reactive oxygen species and subsequent apoptotic cell death. Pretreatment of LLC-PK1 cells with rutin at 5, 10, and 20 μM for 2 hr prior to 2-mM vancomycin exposure for 24 hr significantly decreased intracellular reactive oxygen species and increased superoxide dismutase and catalase activities. Rutin pretreatment also protected cells from vancomycin-induced caspase activation, mitochondrial membrane depolarization, and subsequent apoptosis. This study demonstrates a protective effect of rutin and suggests that rutin coadministration is an alternative therapy for treatment of vancomycin-induced nephrotoxicity.
- Evaluation of urinary 8-hydroxy-2-deoxyguanosine level in experimental Alzheimer's disease: Impact of carvacrol nanoparticles. [Journal Article]
- MBMol Biol Rep 2019 Jun 17
- The present study aimed to compare the effect of carvacrol essential oil and carvacrol nanoemulsion against experimental Alzheimer's (AD). Forty male albino rats were used and divided into four group…
The present study aimed to compare the effect of carvacrol essential oil and carvacrol nanoemulsion against experimental Alzheimer's (AD). Forty male albino rats were used and divided into four groups as follow: control, AlCl3 induced AD, carvacrol oil treated and carvacrol nanoemulsion treated groups. Brain nor-epinephrine, serotonin and dopamine were analyzed by high performance liquid chromatography (HPLC). Levels of brain Thiobarbituric acid-reactive substances (TBARS), Superoxide dismutase (SOD), reduced glutathione (GSH), cholinesterase, and advanced oxidation protein product (AOPP) were evaluated. Urinary 8-hydroxyguanosine (8-OHdG) level was evaluated by HPLC. Brain Cyclooxygenase 1 and 2 (COX 1and 2) were analyzed by immunohistochemistry. AD induced by AlCl3 in rats was depicted by the significant increase in the neurotransmitters levels which is accompanied with high degree of oxidative stress that was revealed in the elevated level of urinary 8-OHdG along with significant elevation in AOPP, TBARS, and cholinesterase levels and a significant decrease in SOD and GSH; these results are confirmed by immunohistochemistry analysis of COX 1 and 2. On the other hand, the treatment with carvacrol oil and carvacrol nanoemulsion were capable of mitigate effects mediated by AlCl3 administration in treated rats. While the treatment with both approached succeeded to retract the negative impact of AlCl3; but the effect of carvacrol nanoemulsion was more notable than the essential oil. Carvacrol oil and carvacrol nanoemulsion were eminent to overturn AlCl3 induced brain AD which could be imputed to antioxidant and anti-inflammatory capabilities of carvacrol to alter oxidative stress effect. In extension; carvacrol nanoemulsion were evident to give more effective and efficient way in carvacrol delivery to pass through blood brain barriers and ameliorate brain changes.
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- Isovitexin reduces carcinogenicity and stemness in hepatic carcinoma stem-like cells by modulating MnSOD and FoxM1. [Journal Article]
- JEJ Exp Clin Cancer Res 2019 Jun 17; 38(1):264
- CONCLUSIONS: Isovitexin inhibits carcinogenicity and stemness in HCSLCs by downregulating FoxM1via inhibition of MnSOD.