scholarly journals Altered Toxicological Endpoints in Humans with Quaternary Ammonium Compound Exposure

2020 ◽  
Author(s):  
Terry C Hrubec ◽  
Ryan P Seguin ◽  
Libin Xu ◽  
Gino A Cortopassi ◽  
Sandipan Datta ◽  
...  
Keyword(s):  
Mitochondrial Function ◽  
Quaternary Ammonium ◽  
Cholesterol Synthesis ◽  
Cholesterol Homeostasis ◽  
Ammonium Compound ◽  
Dependent Manner ◽  
Markers Of Inflammation ◽  
Compound Exposure ◽  
Study Participants ◽  
Dose Dependent

Humans are extensively exposed to Quaternary Ammonium Compounds (QACs). QACs are ubiquitously used in medical settings, restaurants, and homes as cleaners and disinfectants. They are also used on food and in personal care products as preservatives. Despite their prevalence, nothing is known about the health effects associated with chronic low-level exposure. Chronic QAC toxicity was recently identified in mice and resulted in developmental and reproductive deficits and altered immune function. Cell based studies show that QACs increase inflammation, disrupt cholesterol synthesis, and decrease mitochondria function. If these studies translate to human toxicity, multiple physiological functions could be affected. QAC concentrations in humans have not been monitored previously. This study tested whether QAC concentrations could be detected in the blood of 43 random volunteers, and whether QAC concentrations were associated with markers of inflammation, mitochondrial function, and cholesterol synthesis in a dose dependent manner. QAC concentrations were detected in 80% of study participants, and were associated with decreased mitochondrial function and an increase in inflammatory cytokines in a dose dependent manner. Cholesterol synthesis pathway intermediaries were generally increased, indicating disruption in cholesterol homeostasis. This is the first study to demonstrate that chronic exposure to QACs results in measurable concentrations in human blood, and to also demonstrate significant correlations between QAC level and meaningful biomarkers related to health.

scholarly journals Cannabidiol Modulates Mitochondrial Redox and Dynamics in MCF7 Cancer Cells: A Study Using Fluorescence Lifetime Imaging Microscopy of NAD(P)H

2021 ◽  
Vol 8 ◽  
Author(s):  
Rhys Richard Mould ◽  
Stanley W. Botchway ◽  
James R. C. Parkinson ◽  
Elizabeth Louise Thomas ◽  
Geoffrey W Guy ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Fluorescence Lifetime ◽  
Mitochondrial Function ◽  
Mode Of Action ◽  
Fluorescence Lifetime Imaging Microscopy ◽  
Mitochondrial Morphology ◽  
Fluorescence Lifetime Imaging ◽  
Dependent Manner ◽  
Lifetime Imaging ◽  
Dose Dependent

The cannabinoid, cannabidiol (CBD), is part of the plant's natural defense system that when given to animals has many useful medicinal properties, including activity against cancer cells, modulation of the immune system, and efficacy in epilepsy. Although there is no consensus on its precise mode of action as it affects many cellular targets, CBD does appear to influence mitochondrial function. This would suggest that there is a cross-kingdom ability to modulate stress resistance systems that enhance homeostasis. As NAD(P)H autofluorescence can be used as both a metabolic sensor and mitochondrial imaging modality, we assessed the potential of this technique to study the in vitro effects of CBD using 2-photon excitation and fluorescence lifetime imaging microscopy (2P-FLIM) of NAD(P)H against more traditional markers of mitochondrial morphology and cellular stress in MCF7 breast cancer cells. 2P-FLIM analysis revealed that the addition of CBD induced a dose-dependent decrease in bound NAD(P)H, with 20 µM treatments significantly decreased the contribution of bound NAD(P)H by 14.6% relative to the control (p < 0.001). CBD also increased mitochondrial concentrations of reactive oxygen species (ROS) (160 ± 53 vs. 97.6 ± 4.8%, 20 µM CBD vs. control, respectively, p < 0.001) and Ca2+ (187 ± 78 vs. 105 ± 10%, 20 µM CBD vs. the control, respectively, p < 0.001); this was associated with a significantly decreased mitochondrial branch length and increased fission. These are all suggestive of mitochondrial stress. Our results support the use of NAD(P)H autofluorescence as an investigative tool and provide further evidence that CBD can modulate mitochondrial function and morphology in a dose-dependent manner, with clear evidence of it inducing oxidative stress at higher concentrations. This continues to support emerging data in the literature and may provide further insight into its overall mode of action, not only in cancer, but potentially its function in the plant and why it can act as a medicine.

scholarly journals Damaging Effects of Bisphenol A on the Kidney and the Protection by Melatonin: Emerging Evidences from In Vivo and In Vitro Studies

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Anongporn Kobroob ◽  
Wachirasek Peerapanyasut ◽  
Nipon Chattipakorn ◽  
Orawan Wongmekiat
Keyword(s):  
Oxidative Stress ◽  
Bisphenol A ◽  
Mitochondrial Function ◽  
Dependent Manner ◽  
Redox Equilibrium ◽  
Membrane Potential Change ◽  
Kidney Mitochondria ◽  
Dose Dependent

This study investigates the effects of bisphenol A (BPA) contamination on the kidney and the possible protection by melatonin in experimental rats and isolated mitochondrial models. Rats exposed to BPA (50, 100, and 150 mg/kg, i.p.) for 5 weeks demonstrated renal damages as evident by increased serum urea and creatinine and decreased creatinine clearance, together with the presence of proteinuria and glomerular injuries in a dose-dependent manner. These changes were associated with increased lipid peroxidation and decreased antioxidant glutathione and superoxide dismutase. Mitochondrial dysfunction was also evident as indicated by increased reactive oxygen species production, decreased membrane potential change, and mitochondrial swelling. Coadministration of melatonin resulted in the reversal of all the changes caused by BPA. Studies using isolated mitochondria showed that BPA incubation produced dose-dependent impairment in mitochondrial function. Preincubation with melatonin was able to sustain mitochondrial function and architecture and decreases oxidative stress upon exposure to BPA. The findings indicated that BPA is capable of acting directly on the kidney mitochondria, causing mitochondrial oxidative stress, dysfunction, and subsequently, leading to whole organ damage. Emerging evidence further suggests the protective benefits of melatonin against BPA nephrotoxicity, which may be mediated, in part, by its ability to diminish oxidative stress and maintain redox equilibrium within the mitochondria.

scholarly journals Dehydroepiandrosterone Reduced Lipid Droplet Accumulation via Inhibiting Cell Proliferation and Improving Mitochondrial Function in Primary Chicken Hepatocytes

2018 ◽  
pp. 443-456
Author(s):  
L.-L. LI ◽  
D. WANG ◽  
C.-Y. GE ◽  
L. YU ◽  
J.-L. ZHAO ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lipid Droplet ◽  
Mitochondrial Function ◽  
Mitochondrial Membrane ◽  
Lipid Droplets ◽  
Dependent Manner ◽  
Mitochondrial Membrane Permeability ◽  
Cyclin Dependent Kinases ◽  
Dhea Treatment ◽  
Dose Dependent

Dehydroepiandrosterone (DHEA) possesses fat-reducing effect, while little information is available on whether DHEA regulates cell proliferation and mitochondrial function, which would, in turn, affect lipid droplet accumulation in the broiler. In the present study, the lipid droplet accumulation, cell proliferation, cell cycle and mitochondrial membrane potential were analysis in primary chicken hepatocytes after DHEA treated. The results showed that total area and counts of lipid droplets were significantly decreased in hepatocytes treated with DHEA. The cell viability was significantly increased, while cell proliferation was significantly inhibited in a dose dependent manner in primary chicken hepatocytes after DHEA treated. DHEA treatment significantly increased the cell population in S phase and decreased the population in G2/M in primary chicken hepatocytes. Meanwhile, the cyclin A and cyclin-dependent kinases 2 (CDK2) mRNA abundance were significantly decreased in hepatocytes after DHEA treated. No significant differences were observed in the number of mitochondria, while the mitochondrial membrane permeability and succinate dehydrogenase (SDH) activity were significantly increased in hepatocytes after DHEA treated. In conclusion, our results demonstrated that DHEA reduced lipid droplet accumulation by inhibiting hepatocytes proliferation and enhancing mitochondrial function in primary chicken hepatocytes.

scholarly journals Cobalt Chloride Alters Mitochondrial Function in a Dose Dependent Manner

2021 ◽  
Vol 37 (3) ◽  
Author(s):  
Pham Thi Bich ◽  
Vu Thi Thu
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Function ◽  
Mitochondrial Membrane ◽  
Cobalt Chloride ◽  
Dose Dependence ◽  
Cell Counting ◽  
Dependent Manner ◽  
Mitochondrial Oxidative Stress ◽  
H9c2 Cardiomyocytes ◽  
Dose Dependent

Aim: This study was carried to evaluates of Cobalt chloride (CoCl2) on cardiac mitochondrial function. Methods: H9C2 cardiomyocytes were cultured in medium containing different concentrations of CoCl2. Cell viability, cardiolipin content, mitochondrial function, and mitochondrial oxidative stress were assessed by using Cell Counting Kit-8 and suitable fluorescence kits. Results: The obtained data showed that CoCl2 (200÷400 µM) induced cell death and decreased mitochondrial function of H9C2 cardiomyocytes in dose dependence. Especially, CoCl2 at dose of 300 µM significantly altered values of mitochondrial membrane potential, H2O2 and O2- to 63.79±2.15%, 145.81±5.83% and 143.10±3.07% (of 100% control), respectively. Conclusion: CoCl2 strongly induced cardiomyocyte death via altering mitochondrial function in a dose-dependent manner.

scholarly journals Metformin Impairs Mitochondrial Function in Skeletal Muscle of Both Lean and Diabetic Rats in a Dose-Dependent Manner

PLoS ONE ◽  
2014 ◽  
Vol 9 (6) ◽  
pp. e100525 ◽  
Author(s):  
Bart Wessels ◽  
Jolita Ciapaite ◽  
Nicole M. A. van den Broek ◽  
Klaas Nicolay ◽  
Jeanine J. Prompers
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Function ◽  
Diabetic Rats ◽  
Dependent Manner ◽  
Dose Dependent

scholarly journals A Study of C2C12 Myoblast Bioenergetics in Response to the CCG-1423 Rho A Inhibitor

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 689-689
Author(s):  
Bachkhoa Nguyen ◽  
Fathima Ameer ◽  
Jasmine Crane ◽  
Gohar Azhar ◽  
Xiaomin Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Oxygen Consumption ◽  
Mitochondrial Function ◽  
Consumption Rate ◽  
C2c12 Cells ◽  
C2c12 Myoblast ◽  
Dependent Manner ◽  
Mitochondrial Oxygen Consumption ◽  
Myoblast Cells ◽  
Dose Dependent

Abstract CCG-1423 is a Rho A pathway inhibitor which has been reported to inhibit Rho/SRF-mediated transcriptional regulation. SRF and SRF cofactors, which include ternary complex factors (TCFs) and myocardin-related transcription factor (MRTF), regulate various cellular functions. The Rho/SRF signaling pathway also regulates the sirtuin 2 (SIRT2) gene that contains a classic serum response element (SRE) sequence. Current research on CCG-1423 focuses on gene expression levels of SRF in response to CCG-1423 and how SRF levels affect the cells; the studies are focused on cell morphology, migration, viability/reproduction, and overall function. The pathways of this inhibitor have yet to be fully elucidated, but several have been suggested with good evidence. Our goal is to study the effect of CCG-1423 on mitochondrial function and gene expression of cells. In this work C2C12 myoblast cells have been used as an in-vitro model to study cellular bioenergetics and variations in gene expressions induced by CCG-1423. The effect of CCG-1423 on mitochondrial function was determined by measuring the mitochondrial oxygen consumption rate and glycolysis rate after treating C2C12 cells with varying concentrations of CCG-1423 overnight. In C2C12 myoblast cells, CCG-1423 treatment significantly reduced mitochondrial oxygen consumption rate (OCR) in a dose-dependent manner. However, treatment of C2C12 cells with CCG-1423 overnight increased the extracellular acidification rate (ECAR) in a dose-dependent manner. By indicating that CCG-1423 represses mitochondrial respiration via the Rho-SRF signaling pathway, the results of this study may enable a better understanding of the bioenergetics of the cell in the aging body.

Effects of Low Molecular Weight Heparin and Unfragmented Heparin on Induction of Osteoporosis in Rats

1990 ◽  
Vol 63 (03) ◽  
pp. 505-509 ◽  
Author(s):  
Thomas Mätzsch ◽  
David Bergqvist ◽  
Ulla Hedner ◽  
Bo Nilsson ◽  
Per Østergaar
Keyword(s):  
Molecular Weight ◽  
Bone Mineral ◽  
Low Molecular Weight Heparin ◽  
Zinc Content ◽  
Low Molecular Weight ◽  
Dependent Manner ◽  
Bone Mineral Mass ◽  
Bone Ash ◽  
Dose Dependent ◽  
Mineral Mass

SummaryA comparison between the effect of low molecular weight heparin (LMWH) and unfragmented heparin (UH) on induction of osteoporosis was made in 60 rats treated with either UH (2 IU/ g b w), LMWH in 2 doses (2 Xal U/g or 0.4 Xal U/g) or placebo (saline) for 34 days. Studied variables were: bone mineral mass in femora; fragility of humera; zinc and calcium levels in serum and bone ash and albumin in plasma. A significant reduction in bone mineral mass was found in all heparin-treated rats. There was no difference between UH and LMWH in this respect. The effect was dose-dependent in LMWH-treated animals. The zinc contents in bone ash were decreased in all heparin-treated rats as compared with controls. No recognizable pattern was seen in alterations of zinc or calcium in serum. The fragility of the humera, tested as breaking strength did not differ between treatment groups and controls. In conclusion, if dosed according to similar factor Xa inhibitory activities, LMWH induces osteoporosis to the same extent as UH and in a dose-dependent manner. The zinc content in bone ash was decreased after heparin treatment, irrespective of type of heparin given.

Effects of NO-Donors on Thrombus Formation and Microcirculation in Cerebral Vessels of the Rat

1996 ◽  
Vol 76 (01) ◽  
pp. 111-117 ◽  
Author(s):  
Yasuto Sasaki ◽  
Junji Seki ◽  
John C Giddings ◽  
Junichiro Yamamoto
Keyword(s):  
Blood Flow ◽  
Thrombus Formation ◽  
Dependent Manner ◽  
Red Cell ◽  
Cell Velocity ◽  
Red Cell Velocity ◽  
The Mean ◽  
Wall Shear ◽  
Dose Dependent

SummarySodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1), are known to liberate nitric oxide (NO). In this study the effects of SNP and SIN-1 on thrombus formation in rat cerebral arterioles and venules in vivo were assessed using a helium-neon (He-Ne) laser. SNP infused at doses from 10 Μg/kg/h significantly inhibited thrombus formation in a dose dependent manner. This inhibition of thrombus formation was suppressed by methylene blue. SIN-1 at a dose of 100 Μg/kg/h also demonstrated a significant antithrombotic effect. Moreover, treatment with SNP increased vessel diameter in a dose dependent manner and enhanced the mean red cell velocity measured with a fiber-optic laser-Doppler anemometer microscope (FLDAM). Blood flow, calculated from the mean red cell velocity and vessel diameters was increased significantly during infusion. In contrast, mean wall shear rates in the arterioles and venules were not changed by SNP infusion. The results indicated that SNP and SIN-1 possessed potent antithrombotic activities, whilst SNP increased cerebral blood flow without changing wall shear rate. The findings suggest that the NO released by SNP and SIN-1 may be beneficial for the treatment and protection of cerebral infarction

Melatonin actions in the heart; more than a hormone

2018 ◽  
Vol 1 (1) ◽  
pp. 21-26 ◽  
Author(s):  
Darío Acuña-Castroviejo ◽  
Maria T Noguiera-Navarro ◽  
Russel J Reiter ◽  
Germaine Escames
Keyword(s):  
Cell Membranes ◽  
Myocardial Cell ◽  
Rat Tissues ◽  
Dependent Manner ◽  
Broad Distribution ◽  
Multiple Organs ◽  
High Doses ◽  
Extrapineal Melatonin ◽  
Dose Dependent ◽  
Different Doses

Due to the broad distribution of extrapineal melatonin in multiple organs and tissues, we analyzed the presence and subcellular distribution of the indoleamine in the heart of rats. Groups of sham-operated and pinealectomized rats were sacrificed at different times along the day, and the melatonin content in myocardial cell membranes, cytosol, nuclei and mitochondria, were measured. Other groups of control animals were treated with different doses of melatonin to monitor its intracellular distribution. The results show that melatonin levels in the cell membrane, cytosol, nucleus, and mitochondria vary along the day, without showing a circadian rhythm. Pinealectomized animals trend to show higher values than sham-operated rats. Exogenous administration of melatonin yields its accumulation in a dose-dependent manner in all subcellular compartments analyzed, with maximal concentrations found in cell membranes at doses of 200 mg/kg bw melatonin. Interestingly, at dose of 40 mg/kg b.w, maximal concentration of melatonin was reached in the nucleus and mitochondrion. The results confirm previous data in other rat tissues including liver and brain, and support that melatonin is not uniformly distributed in the cell, whereas high doses of melatonin may be required for therapeutic purposes.

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