scholarly journals Ginkgolide B Maintains Calcium Homeostasis in Hypoxic Hippocampal Neurons by Inhibiting Calcium Influx and Intracellular Calcium Release

2021 ◽  
Vol 14 ◽  
Author(s):  
Li Wang ◽  
Quan Lei ◽  
Shuai Zhao ◽  
WenJuan Xu ◽  
Wei Dong ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Calcium Release ◽  
Calcium Influx ◽  
Brain Slices ◽  
Spontaneous Discharge ◽  
Protective Effects ◽  
Ginkgolide B ◽  
Pre Treatment

Ginkgolide B (GB), a terpene lactone and active ingredient of Ginkgo biloba, shows protective effects in neuronal cells subjected to hypoxia. We investigated whether GB might protect neurons from hypoxic injury through regulation of neuronal Ca2+ homeostasis. Primary hippocampal neurons subjected to chemical hypoxia (0.7 mM CoCl2) in vitro exhibited an increase in cytoplasmic Ca2+ (measured from the fluorescence of fluo-4), but this effect was significantly diminished by pre-treatment with 0.4 mM GB. Electrophysiological recordings from the brain slices of rats exposed to hypoxia in vivo revealed increases in spontaneous discharge frequency, action potential frequency and calcium current magnitude, and all these effects of hypoxia were suppressed by pre-treatment with 12 mg/kg GB. Western blot analysis demonstrated that hypoxia was associated with enhanced mRNA and protein expressions of Cav1.2 (a voltage-gated Ca2+ channel), STIM1 (a regulator of store-operated Ca2+ entry) and RyR2 (isoforms of Ryanodine Receptor which mediates sarcoplasmic reticulum Ca2+ release), and these actions of hypoxia were suppressed by GB. Taken together, our in vitro and in vivo data suggest that GB might protect neurons from hypoxia, in part, by regulating Ca2+ influx and intracellular Ca2+ release to maintain Ca2+ homeostasis.

scholarly journals Protective Effects of Scolopendra Water Extract on Trimethyltin-Induced Hippocampal Neurodegeneration and Seizures in Mice

2019 ◽  
Vol 9 (12) ◽  
pp. 369
Author(s):  
Yun-Soo Seo ◽  
Mary Jasmin Ang ◽  
Byeong Cheol Moon ◽  
Hyo Seon Kim ◽  
Goya Choi ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Primary Cultures ◽  
Water Extract ◽  
Model Systems ◽  
Inflammatory Factor ◽  
Dependent Manner ◽  
Protective Effects ◽  
Cell Degeneration

Trimethyltin (TMT) is an organotin compound with potent neurotoxic action characterized by neuronal degeneration in the hippocampus. This study evaluated the protective effects of a Scolopendra water extract (SWE) against TMT intoxication in hippocampal neurons, using both in vitro and in vivo model systems. Specifically, we examined the actions of SWE on TMT- (5 mM) induced cytotoxicity in primary cultures of mouse hippocampal neurons (7 days in vitro) and the effects of SWE on hippocampal degeneration in adult TMT- (2.6 mg/kg, intraperitoneal) treated C57BL/6 mice. We found that SWE pretreatment (0–100 μg/mL) significantly reduced TMT-induced cytotoxicity in cultured hippocampal neurons in a dose-dependent manner, as determined by lactate dehydrogenase and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assays. Additionally, this study showed that perioral administration of SWE (5 mg/kg), from −6 to 0 days before TMT injection, significantly attenuated hippocampal cell degeneration and seizures in adult mice. Furthermore, quantitative analysis of Iba-1 (Allograft inflammatory factor 1)- and GFAP (Glial fibrillary acidic protein)-immunostained cells revealed a significant reduction in the levels of Iba-1- and GFAP-positive cell bodies in the dentate gyrus (DG) of mice treated with SWE prior to TMT injection. These data indicated that SWE pretreatment significantly protected the hippocampus against the massive activation of microglia and astrocytes elicited by TMT. In addition, our data showed that the SWE-induced reduction of immune cell activation was linked to a significant reduction in cell death and a significant improvement in TMT-induced seizure behavior. Thus, we conclude that SWE ameliorated the detrimental effects of TMT toxicity on hippocampal neurons, both in vivo and in vitro. Altogether, our findings hint at a promising pharmacotherapeutic use of SWE in hippocampal degeneration and dysfunction.

scholarly journals IL-22 ameliorates LPS-induced acute liver injury by autophagy activation through ATF4-ATG7 signaling

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Lujing Shao ◽  
Xi Xiong ◽  
Yucai Zhang ◽  
Huijie Miao ◽  
Yuqian Ren ◽  
...  
Keyword(s):  
Liver Injury ◽  
Inflammatory Responses ◽  
Acute Liver Injury ◽  
Mrna Levels ◽  
Protective Effects ◽  
Activating Transcription Factor 4 ◽  
Pre Treatment ◽  
Underlying Mechanisms

Abstract Uncontrollable inflammatory response acts as a driver of sepsis-associated liver injury (SALI). IL-22 plays an important role in regulating inflammatory responses, but its role in SALI remains unknown. The aim of the study was to assess the association of serum IL-22 with SALI in pediatric patients and to enclose the underlying mechanisms of IL-22 involved in lipopolysaccharide (LPS) - induced acute liver injury (ALI) in mice. Serum IL-22 levels in patients with SALI were significantly lower than in septic patients without liver injury, and the area under receiver operating characteristic (ROC) curve of IL-22 for discriminating SALI was 0.765 (95% CI: 0.593–0.937). Pre-administration of recombinant murine IL-22 alleviated LPS-induced ALI in mice, and serum IL-6 levels and the mRNA levels of TNF-α, IL-1β, and IL-6 in livers were decreased in response to IL-22 pre-treatment in mice. More importantly, IL-22 pre-treatment activated hepatic autophagy mediated by activating transcription factor 4 (ATF4)-autophagy-related gene 7 (ATG7) signaling in vivo and in vitro in response to LPS administration. Moreover, knockdown of ATF4 in mice aggravated LPS-induced ALI, which was associated with suppressed ATG7-related autophagy. In addition, the protective effects of IL-22 on LPS-induced ALI was partially blocked by ATF4 knockdown, which was associated with lower expression of LC3II/I in the livers of ATF4 knockdown (HT or Atf4+/−) mice compared with wild-type mice (WT or Atf4+/+) mice. In conclusion, low serum IL-22 level is associated with SALI occurrence, and IL-22 pre-administration activates autophagy in hepatocytes and protects mice against LPS-induced ALI partially related to ATF4-ATG7 signaling pathway.

scholarly journals Action potentials and amphetamine release antipsychotic drug from dopamine neuron synaptic VMAT vesicles

2015 ◽  
Vol 112 (32) ◽  
pp. E4485-E4494 ◽  
Author(s):  
Kristal R. Tucker ◽  
Ethan R. Block ◽  
Edwin S. Levitan
Keyword(s):  
Action Potentials ◽  
Hippocampal Neurons ◽  
D2 Receptor ◽  
Brain Slices ◽  
Ph Gradients ◽  
Dopaminergic Transmission ◽  
Two Photon Microscopy ◽  
Two Photon

Based on lysotracker red imaging in cultured hippocampal neurons, antipsychotic drugs (APDs) were proposed to accumulate in synaptic vesicles by acidic trapping and to be released in response to action potentials. Because many APDs are dopamine (DA) D2 receptor (D2R) antagonists, such a mechanism would be particularly interesting if it operated in midbrain DA neurons. Here, the APD cyamemazine (CYAM) is visualized directly by two-photon microscopy in substantia nigra and striatum brain slices. CYAM accumulated slowly into puncta based on vacuolar H+-ATPase activity and dispersed rapidly upon dissipating organelle pH gradients. Thus, CYAM is subject to acidic trapping and released upon deprotonation. In the striatum, Ca2+-dependent reduction of the CYAM punctate signal was induced by depolarization or action potentials. Striatal CYAM overlapped with the dopamine transporter (DAT). Furthermore, parachloroamphetamine (pCA), acting via vesicular monoamine transporter (VMAT), and a charged VMAT, substrate 1-methyl-4-phenylpyridinium (MPP+), reduced striatal CYAM. In vivo CYAM administration and in vitro experiments confirmed that clinically relevant CYAM concentrations result in vesicular accumulation and pCA-dependent release. These results show that some CYAM is in DA neuron VMAT vesicles and suggests a new drug interaction in which amphetamine induces CYAM deprotonation and release as a consequence of the H+ countertransport by VMAT that accompanies vesicular uptake, but not by inducing exchange or acting as a weak base. Therefore, in the striatum, APDs are released with DA in response to action potentials and an amphetamine. This synaptic corelease is expected to enhance APD antagonism of D2Rs where and when dopaminergic transmission occurs.

Enhanced vascular reactivity to various vasoconstrictor agents following pinealectomy in the rat: role of melatonin

1980 ◽  
Vol 58 (3) ◽  
pp. 287-293 ◽  
Author(s):  
Stephen C. Cunnane ◽  
Mehar S. Manku ◽  
Masatsugu Oka ◽  
David F. Horrobin
Keyword(s):  
Vascular Reactivity ◽  
Calcium Release ◽  
Calcium Influx ◽  
Extracellular Fluid ◽  
Heart Weight ◽  
Vasoconstrictor Agents ◽  
Vascular Responsiveness ◽  
Male Wistar Rats

The mesenteric vascular bed preparation of control and pinealectomized (PX) male Wistar rats was used to examine vascular reactivity to two concentrations each of norepinephrine, serotonin, angiotensin, and potassium. Vasoconstrictor responses to 50- and 100-ng injections of norepinephrine and 0.5- and 1.0-μg injections of serotonin were 30–40% higher in preparations from PX rats. Responses to 100 ng but not to 50 ng of angiotensin were also significantly higher in preparations from PX rats. Responses to 1.5- and to 3.0-mg injections of potassium did not differ significantly in either case. In vivo injection of 20 μg of melatonin 3 h prior to dissection of the preparation, or in vitro perfusion of 20 ng melatonin per millilitre of buffer completely reversed the increased vascular response to all vasoconstrictor agents tested in the PX preparations, but had little effect in control preparations. Also observed in PX rats was a significant increase in blood pressure, serum sodium, and increased body and heart weight. Arterial wall sodium was also elevated in PX rats. These changes may be relevant to the increased vascular reactivity of PX rats. The increased vascular responsiveness of PX rats may be specific for agents that stimulate calcium release from intracellular stores (norepinephrine, angiotensin) rather than those that stimulate calcium influx from extracellular fluid (potassium). Melatonin lack may be the cause of the vascular changes in the PX rats as both in vivo and in vitro it lowered the vasoconstrictor effects of the agents tested, but only in PX rats; it had no significant effect in the control rats.

scholarly journals Azithromycin ameliorates sulfur dioxide-induced airway epithelial damage and inflammatory responses

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Jon Petur Joelsson ◽  
Jennifer A. Kricker ◽  
Ari J. Arason ◽  
Snaevar Sigurdsson ◽  
Bryndis Valdimarsdottir ◽  
...  
Keyword(s):  
Sulfur Dioxide ◽  
Airway Epithelium ◽  
Inflammatory Responses ◽  
Protein Composition ◽  
Lavage Fluid ◽  
Protective Effects ◽  
Barrier Dysfunction ◽  
Pre Treatment

Abstract Background The airway epithelium (AE) forms the first line of defence against harmful particles and pathogens. Barrier failure of the airway epithelium contributes to exacerbations of a range of lung diseases that are commonly treated with Azithromycin (AZM). In addition to its anti-bacterial function, AZM has immunomodulatory effects which are proposed to contribute to its clinical effectiveness. In vitro studies have shown the AE barrier-enhancing effects of AZM. The aim of this study was to analyze whether AE damage caused by inhalation of sulfur dioxide (SO2) in a murine model could be reduced by pre-treatment with AZM. Methods The leakiness of the AE barrier was evaluated after SO2 exposure by measuring levels of human serum albumin (HSA) in bronchoalveolar lavage fluid (BALF). Protein composition in BALF was also assessed and lung tissues were evaluated across treatments using histology and gene expression analysis. Results AZM pre-treatment (2 mg/kg p.o. 5 times/week for 2 weeks) resulted in reduced glutathione-S-transferases in BALF of SO2 injured mice compared to control (without AZM treatment). AZM treated mice had increased intracellular vacuolization including lamellar bodies and a reduction in epithelial shedding after injury in addition to a dampened SO2-induced inflammatory response. Conclusions Using a mouse model of AE barrier dysfunction we provide evidence for the protective effects of AZM in vivo, possibly through stabilizing the intracellular microenvironment and reducing inflammatory responses. Our data provide insight into the mechanisms contributing to the efficacy of AZM in the treatment of airway diseases.

Protective Effects of Low Dose Vorinostat on Cisplatin-induced Nephrotoxicity in Rats

2020 ◽  
Vol 13 ◽  
Author(s):  
Omnyah M. O. Bashraf ◽  
Ahmed S. Ali ◽  
Hala S. A. Eweis ◽  
Soad S. Ali
Keyword(s):  
Single Dose ◽  
Therapeutic Potential ◽  
Control Group ◽  
Histopathological Analysis ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
In Vivo Models ◽  
Pre Treatment

Background and Aim: Cisplatin (cis-diamminedichloroplatinum [II]; CDDP) is the most widely used drug in cancer chemotherapy. The nephrotoxicity of CDDP is one of its major side effects. Vorinostat (VST) has been reported to have antioxidant and anti-inflammatory effects in both in-vitro and in vivo models. The present study aimed to explore the potential protective effects of VST against CDDP-induced nephrotoxicity in rats. Materials and Methods: The rats were randomly divided into 4 groups; control group, CDDP group (received CDDP 7.5 mg/kg IP single dose 5 days before the end of the experiment), VST group, (received VST 15 mg/kg/day by gastric gavage for 28 days), and CDDP + VST group (received CDDP + VST as above). Blood and kidney samples were collected on the 28th day for biochemical and histopathological examinations. Results : Administration of CDDP single dose (7.5 mg/kg IP) 5 days before the end of the experiment (at day 23) produced a significant decrease in renal glutathione levels and a significant increase in serum urea nitrogen, creatinine, renal malondialdehyde, tumor necrosis factor-alpha, tumor suppressor protein (p53) and nuclear factor kappa B levels compared to the control group. Pre-treatment with VST for 28 days significantly attenuated all unfavorable changes of these parameters. Histopathological analysis showed that VST significantly decreased kidney inflammatory and degenerative changes induced by CDDP. VST also significantly increased Bcl-2 and decreased Caspas-3 immunoexpression in renal tissues. Conclusion: These results suggest that VST alleviates CDDP-induced nephrotoxicity in rats showing a novel therapeutic potential for the management of nephrotoxicity induced by CDDP.

scholarly journals A Herbal Mixture Formula of OCD20015-V009 Prophylactic Administration to Enhance Interferon-Mediated Antiviral Activity Against Influenza A Virus

2021 ◽  
Vol 12 ◽  
Author(s):  
Eun-Bin Kwon ◽  
You-Chang Oh ◽  
Youn-Hwan Hwang ◽  
Wei Li ◽  
Seok-Man Park ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Influenza A Virus ◽  
Influenza A ◽  
Type I ◽  
Protective Effects ◽  
Murine Macrophages ◽  
Prophylactic Administration ◽  
Pre Treatment

OCD20015-V009 is an herbal mix of water-extracted Ginseng Radix, Poria (Hoelen), Rehmanniae Radix, Adenophorae Radix, Platycodi Radix, Crataegii Fructus, and Astragali Radix. In this study, its in vitro and in vivo antiviral activity and mechanisms against the influenza A virus were evaluated using a GFP-tagged influenza A virus (A/PR/8/34-GFP) to infect murine macrophages. We found that OCD20015-V009 pre-treatment substantially reduced A/PR/8/34-GFP replication. Also, OCD20015-V009 pre-treatment increased the phosphorylation of type-I IFN-related proteins TBK-1 and STAT1 and the secretion of pro-inflammatory cytokines TNF-α and IL-6 by murine macrophages. Moreover, OCD20015-V009 prophylactic administration increased IFN-stimulated genes-related 15, 20, and 56 and IFN-β mRNA in vitro. Thus, OCD20015-V009 likely modulates murine innate immune response via macrophages. This finding is potentially useful for developing prophylactics or therapeutics against the influenza A virus. Furthermore, pre-treatment with OCD20015-V009 decreased the mortality of the mice exposed to A/PR/8/34-GFP by 20% compared to that in the untreated animals. Thus, OCD20015-V009 stimulates the antiviral response in murine macrophages and mice to viral infections. Additionally, we identified chlorogenic acid and ginsenoside Rd as the antiviral components in OCD20015-V009. Further investigations are needed to elucidate the protective effects of active components of OCD20015-V009 against influenza A viruses.

scholarly journals Mechanisms of Dendritic Calcium Signaling in Fly Neurons

2001 ◽  
Vol 85 (1) ◽  
pp. 439-447 ◽  
Author(s):  
Thomas G. Oertner ◽  
Tilmann M. Brotz ◽  
Alexander Borst
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Calcium Release ◽  
Visual Stimulation ◽  
Calcium Influx ◽  
Calcium Signal ◽  
Lobula Plate ◽  
Calcium Accumulation

We examined the mechanisms underlying dendritic calcium accumulation in lobula plate tangential cells of the fly visual system using an in vitro preparation of the fly brain. Local visual stimulation evokes a localized calcium signal in the dendrites of these cells in vivo. Here we show that a similar localized calcium accumulation can be elicited in vitro by focal iontophoretic application of the cholinergic agonist carbachol. The calcium signal had at least two sources: first, voltage-dependent calcium channels contributed to the carbachol-induced signal and were concentrated on the dendrite, the soma, and the terminal ramification of the axon. However, the dendritic calcium signal induced by carbachol stimulation was only weakly dependent on membrane depolarization. The most likely explanation for the second, voltage-independent part of the dendritic calcium signal is calcium entry through nicotinic acetylcholine receptors. We found no indication of second-messenger or calcium-mediated calcium release from intracellular stores. In summary, the characteristic spatiotemporal calcium signals in the dendrites of lobula plate tangential cells can be reproduced in vitro, and result from a combination of voltage- and ligand-gated calcium influx.

scholarly journals Montelukast Protects Against Renal Damage Due to Cadmium Toxicity: In vivo and In vitro Experiments

2021 ◽  
Vol 15 (4) ◽  
pp. 223-232
Author(s):  
Farnoosh Kaviani ◽  
◽  
Missagh Jalali ◽  
Elham Hoveizi ◽  
Javad Jamshidian ◽  
...  
Keyword(s):  
Vitamin E ◽  
Cell Damage ◽  
Cadmium Toxicity ◽  
Antioxidant Properties ◽  
Protective Effects ◽  
Human Embryonic Kidney Cells ◽  
Pre Treatment ◽  
Gpx Activity

Background: The protective effects of Montelukast (Mont), as an anti-inflammatory drug, against cadmium-induced kidney cell damage have already been studied and identified. Since the significant part of cadmium nephrotoxicity is caused by oxidative stress, this in vivo and in vitro study was conducted to investigate the possible role of Montelukast antioxidant properties in the protection. Methods: In the in vivo section, 42 rats were treated in seven groups of six rats as follows: Control; Cadmium Chloride (CdCl2) control; Montelukast control; CdCl2 plus Montelukast treatment; CdCl2 with Montelukast pre-treatment; Vitamin E control; CdCl2 plus Vitamin E treatment. In the in vitro section, human embryonic kidney cells (HEK293) were treated with CdCl2; Montelukast; Combined CdCl2 and Montelukast; Vitamin E; Combined CdCl2 and Vitamin E. Results: Montelukast, in both treatment and pretreatment forms, reduced serum urea, creatinine, and potassium levels compared to CdCl2 group, in vivo. Similar to vitamin E, the pre-treatment with Montelukast was associated with a significant decrease in Nitric Oxide (NO) and Total Antioxidant Capacity (TAC) in serum and renal tissue, and a significant increase in Glutathione Peroxidase (GPX) activity in serum compared those in the CdCl2 group. In the in vitro section of the study, Montelukast significantly reduced Malondialdehyde (MDA) and NO while the TAC level, Superoxide Dismutase (SOD), and the GPX activity increased significantly. Conclusion: Overall, the antioxidant effects of Montelukast appear to play a prominent role in preventing the renal toxicity due to cadmium exposure.

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