scholarly journals Protective Role of a Donepezil-Huprine Hybrid against the β-Amyloid (1-42) Effect on Human Erythrocytes

2021 ◽  
Vol 22 (17) ◽  
pp. 9563
Author(s):  
Pablo Zambrano ◽  
Mario Suwalsky ◽  
Malgorzata Jemiola-Rzeminska ◽  
María José Gallardo-Nelson ◽  
Kazimierz Strzalka ◽  
...  

Aβ(1-42) peptide is a neurotoxic agent strongly associated with the etiology of Alzheimer’s disease (AD). Current treatments are still of very low effectiveness, and deaths from AD are increasing worldwide. Huprine-derived molecules have a high affinity towards the enzyme acetylcholinesterase (AChE), act as potent Aβ(1-42) peptide aggregation inhibitors, and improve the behavior of experimental animals. AVCRI104P4 is a multitarget donepezil-huprine hybrid that improves short-term memory in a mouse model of AD and exerts protective effects in transgenic Caenorhabditis elegans that express Aβ(1-42) peptide. At present, there is no information about the effects of this compound on human erythrocytes. Thus, we considered it important to study its effects on the cell membrane and erythrocyte models, and to examine its protective effect against the toxic insult induced by Aβ(1-42) peptide in this cell and models. This research was developed using X-ray diffraction and differential scanning calorimetry (DSC) on molecular models of the human erythrocyte membrane constituted by lipid bilayers built of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE). They correspond to phospholipids representative of those present in the external and internal monolayers, respectively, of most plasma and neuronal membranes. The effect of AVCRI104P4 on human erythrocyte morphology was studied by scanning electron microscopy (SEM). The experimental results showed a protective effect of AVCRI104P4 against the toxicity induced by Aβ(1-42) peptide in human erythrocytes and molecular models.

Author(s):  
S. A. Livesey ◽  
A. A. del Campo ◽  
E. S. Griffey ◽  
D. Ohlmer ◽  
T. Schifani ◽  
...  

The aim of this study is to compare methods of sample preparation for elemental analysis. The model system which is used is the human erythrocyte. Energy dispersive spectroscopic analysis has been previously reported for cryofixed and cryosectioned erythrocytes. Such work represents the reference point for this study. The use of plastic embedded samples for elemental analysis has also been documented. The work which is presented here is based on human erythrocytes which have been either chemically fixed and embedded or cryofixed and subsequently processed by a variety of techniques which culminated in plastic embedded samples.Heparinized and washed erythrocytes were prepared by the following methods for this study :(1). Chemical fixation in 4% paraformaldehyde/0.25% glutaraldehyde/0.2 M sucrose in 0.1 M Na cacodylate, pH 7.3 for 30 min, followed by ethanol dehydration, infiltration and embedding in Lowicryl K4M at -20° C.


2020 ◽  
Vol 26 ◽  
Author(s):  
Abdulqader Fadhil Abed ◽  
Yazun Bashir Jarrar ◽  
Hamzeh J Al-Ameer ◽  
Wajdy Al-Awaida ◽  
Su-Jun Lee

Background: Oxandrolone is a synthetic testosterone analogue that is widely used among bodybuilders and athletes. However, oxandrolone causes male infertility. Recently, it was found that metformin reduces the risk of infertility associated with diabetes mellitus. Aim: This study aimed to investigate the protective effects of metformin against oxandrolone-induced infertility in male rats. Methods: Rats continuously received one of four treatments (n=7) over 14 days: control DMSO administration, oxandrolone administration, metformin administration, or co-administration of oxandrolone and metformin. Doses were equivalent to those used for human treatment. Subsequently, testicular and blood samples were collected for morphological, biochemical, and histological examination. In addition, gene expression of the testosterone synthesizing enzyme CYP11A1 was analyzed in the testes using RT-PCR. Results: Oxandrolone administration induced male infertility by significantly reducing relative weights of testes by 48%, sperm count by 82%, and serum testosterone levels by 96% (ANOVA, P value < 0.05). In addition, histological examination determined that oxandrolone caused spermatogenic arrest which was associated with 2-fold downregulation of testicular CYP11A1 gene expression. However, co-administration of metformin with oxandrolone significantly ameliorated toxicological alterations induced by oxandrolone exposure (ANOVA, P value < 0.05). Conclusion: Metformin administration protected against oxandrolone-induced infertility in male rats. Further clinical studies are needed to confirm the protective effect of metformin against oxandrolone-induced infertility among athletes.


Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 479
Author(s):  
Seong Hoon Kim ◽  
Hye-Won Yum ◽  
Seung Hyeon Kim ◽  
Wonki Kim ◽  
Su-Jung Kim ◽  
...  

Taurine chloramine (TauCl) is an endogenous anti-inflammatory substance which is derived from taurine, a semi-essential sulfur-containing β-amino acid found in some foods including meat, fish, eggs and milk. In general, TauCl as well as its parent compound taurine downregulates production of tissue-damaging proinflammatory mediators, such as chemokines and cytokines in many different types of cells. In the present study, we investigated the protective effects of TauCl on experimentally induced colon inflammation. Oral administration of TauCl protected against mouse colitis caused by 2,4,6-trinitrobenzene sulfonic acid (TNBS). TauCl administration attenuated apoptosis in the colonic mucosa of TNBS-treated mice. This was accompanied by reduced expression of an oxidative stress marker, 4-hydroxy-2-nonenal and proinflammatory molecules including tumor necrosis factor-α, interleukin-6 and cyclooxygenase-2 in mouse colon. TauCl also inhibited activation of NFκB and STAT3, two key transcription factors mediating proinflammatory signaling. Notably, the protective effect of TauCl on oxidative stress and inflammation in the colon of TNBS-treated mice was associated with elevated activation of Nrf2 and upregulation of its target genes encoding heme oxygenase-1, NAD(P)H:quinone oxidoreductase, glutamate cysteine ligase catalytic subunit, and glutathione S-transferase. Taken together, these results suggest that TauCl exerts the protective effect against colitis through upregulation of Nrf2-dependent cytoprotective gene expression while blocking the proinflammatory signaling mediated by NFκB and STAT3.


1999 ◽  
Vol 18 (5) ◽  
pp. 327-332 ◽  
Author(s):  
J V Calderón-Salinas ◽  
M A Quintanar-Escorcia ◽  
M T González-Martínez ◽  
C E Hernández-Luna

In this paper we report the lead (Pb) and calcium (Ca) uptake by erythrocyte ghosts. In both cases the transport was carried out by a passive transport system with two kinetic components (Michaelis-Menten and Hill). Pb and Ca were capable of inhibiting the transport of the other metal in a non-competitive way. Under hyperpolarization, the uptakes of Ca and Pb were enhanced and the Michaelis-Menten component prevailed. Both Ca and Pb uptakes were inhibited by N-ethyl-maleimide to the same extent. These results indicate that Pb and Ca share the same permeability pathway in human erythrocytes and that this transport system is electrogenic.


1977 ◽  
Vol 165 (1) ◽  
pp. 157-161 ◽  
Author(s):  
M J A Tanner ◽  
D J Anstee ◽  
P A Judson

1. We investigated the membranes of human erythrocytes which completely lack the blood-group antigens S and s (denoted as S-s-) as part of a study of the structure and function of the surface glycoproteins of the human erythrocyte. 2. The S-s-erythrocyte-membrane glycoprotein PAS-3 band was much less intensely stained in comparison with that of the glycoprotein from normal erythrocyte membranes. The S-s-membrane glycoprotein PAS-4 band also showed decreased staining. 3. Examination with the lectins from Maclura aurantiaca (Osage orange) and Arachis hypogaea (groundnut) showed that the PAS-3 glycoprotein of S-s-erythrocyte membranes lacked the receptors for these lectins that are present on glycoprotein PAS-3 from normal erythrocytes. 4. Radioiodination with lactoperoxidase showed the presence of the polypeptide of glycoprotein PAS-3 in S-s-cells, although it was more weakly labelled than the protein in the normal erythrocyte. 5. Our results show that the PAS-3 glycoprotein of S-s-erythrocytes is deficient in some of the carbohydrates present in the protein from normal erythrocytes. Glycoprotein PAS-4 of normal erythrocytes is shown to be a complex containing both glycoproteins PAS-1 and PAS-3.


Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Ahmed A Elmarakby ◽  
Jessica Faulkner ◽  
Chelsey Pye ◽  
Babak Baban ◽  
Katelyn Rouch ◽  
...  

We previously showed that inhibition of soluble epoxide hydrolase (sEH) increased epoxyeicosatrienoic acids (EETs) levels and reduced renal injury in diabetic mice and these changes were associated with induction of hemeoxygenase-1 (HO-1). The present study determines whether the inhibition of HO negates the reno-protective effect of sEH inhibition in diabetic spontaneously hypertensive rats as a model of diabetic nephropathy in which hypertension coexists with diabetes. After six weeks of induction of diabetes with streptozotocin, SHR were divided into the following groups: untreated, treated with the sEH inhibitor, trans -4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (AUCB), treated with the HO inhibitor, stannous mesoporphyrin (SnMP), and treated with both inhibitors for four more weeks; non diabetic SHR served as a control group. Although inhibition of sEH increased renal EETs/DHETEs ratio and HO-1 activity in diabetic SHR, it did not significantly alter blood pressure (plasma EETs/DHETEs ratio was 0.5± 0.1 in AUCB-treated vs. 0.1± 0.01 in untreated diabetic SHR, P<0.05). Treatment of diabetic SHR with AUCB reduced the elevation in urinary albumin and nephrin excretion (albuminuria was 6.5± 0.5 in AUCB-treated diabetic SHR vs. 9± 1.7 mg/day in untreated diabetic SHR and nephrinuria was 70±11 in AUCB-treated diabetic SHR vs. 111± 9 μg/day in untreated diabetic SHR, P<0.05) whereas co-administration of SnMP with AUCB prevented these changes (albuminuria was 10.6± 0.6 mg/day and nephrinuria was 91±11 μg/day). Immunohistochemical analysis revealed elevations in renal fibrosis and apoptosis as evidenced by increased renal TGF-β, fibronectin and annexin V expression in diabetic SHR and these changes were reduced with sEH inhibition. Co-administration of SnMP with AUCB prevented its ability to reduce renal fibrosis and apoptosis in diabetic SHR. In addition, SnMP treatment also prevented AUCB-induced decreases in renal macrophage infiltration and renal TGF-β, NFκB and MCP-1 levels in diabetic SHR. These data suggest that HO-1 induction is involved in the protective effect of sEH inhibition against diabetic renal injury.


2019 ◽  
Vol 1861 (1) ◽  
pp. 17-25 ◽  
Author(s):  
Karla Petit ◽  
Mario Suwalsky ◽  
José R. Colina ◽  
Luis F. Aguilar ◽  
Malgorzata Jemiola-Rzeminska ◽  
...  

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Sheng-Yong Luo ◽  
Qing-Hua Xu ◽  
Gong Peng ◽  
Zhi-Wu Chen

Objectives. Total flavones from Rhododendron simsii Planch. (TFR) are the effective part extracted from the flowers of Rhododendron simsii Planch. and have obvious protective effects against cerebral ischemic or myocardial injuries in rabbits and rats. However, their mechanism of cardioprotection is still unrevealed. Therefore, the present study was designed to investigate the effect of TFR on myocardial I/R injury and the underlying mechanism. Methods. TFR groups were treated by gavage once a day for 3 days at a dose of 20, 40, and 80 mg/kg, respectively, and then the model of myocardial I/R injury was established. Myocardial infarction, ST-segment elevation, and the expression of UTR, ROCK1, ROCK2, and p-MLC protein in rat myocardium were determined at 90 min after reperfusion. UTR siRNA in vivo transfection and competition binding assay method were used to study the relationship between the protective effect of TFR and UTR. Results. The expression of UTR protein markedly decreased in myocardium of UTR siRNA transfection group rats. TFR could significantly reduce the infarct size and inhibit the increase of RhoA activity and ROCK1, ROCK2, and p-MLC protein expressions both in WT and UTR knockdown rats. The reducing rate of TFR in myocardial infarction area, RhoA activity, and ROCK1, ROCK2, and p-MLC protein expressions in UTR knockdown rats decreased markedly compared with that in WT rats. In addition, TFR had no obvious effect on the increase of ΣST in UTR knockdown rats in comparison with that in model group. In particular, TFR could significantly inhibit the combination of [I125]-hu-II and UTR, and IC50 was 0.854 mg/l. Conclusions. The results indicate that the protective effect of TFR on I/R injury may be correlated with its blocking UTR and the subsequent inhibition of RhoA/ROCK signaling pathway.


2019 ◽  
Vol 64 (3) ◽  
pp. 132-139
Author(s):  
P. S. Usoltseva ◽  
A. V. Alimov ◽  
A. V. Rezaykin ◽  
A. G. Sergeev ◽  
A. V. Novoselov

The aim of this study was to determine the role of the human neonatal receptor for the Fc fragment of IgG (hFcRn) as a common uncoating cellular receptor for echoviruses and coxsackievirus A9 during infection of human rhabdomyosarcoma (RD) cells. Material and methods. The protective effect of the human serum albumin, purified from globulins, (HSA-GF) and antibodies to hFcRn was studied in RD cells infected with several strains and clones of species B enteroviruses possessing different receptor specificity (echoviruses 3, 9, 11, 30 and coxsackieviruses A9, B4, B5). Results. It was shown that HSA-GF at concentrations of 4% or less protected RD cells from infection with echoviruses 3, 9, 11 and coxsackievirus A9. The antibodies to hFcRn at concentrations of 2.5 ug/mL or less demonstrated the similar spectrum of protective activity in RD cells against infection with echoviruses 3, 9, 11, 30 and coxsackievirus A9. The protective effect of HSA-GF or the antibodies to hFcRn was not observed in RD cells infected with coxsackieviruses B4 and B5 that need coxsackievirus-adenovirus receptor for uncoating. Discussion. The usage of the previously characterized echovirus 11 clonal variants with different receptor specificity allowed us to define the function of hFcRn as a canyon-binding uncoating receptor in RD cells. The kinetics and magnitude of the observed protective effects correlated with receptor specificity of the enteroviruses used in this work supporting the two-step interaction of DAF-dependent echoviruses with the cellular receptors. Conclusions. In this study, the function of hFcRn was defined in RD cells as a canyon-binding and uncoating receptor for echoviruses and coxsackievirus A9. The two-step interaction of DAF-dependent echoviruses during entry into the cells was confirmed: initially with the binding receptor DAF and subsequently with the uncoating receptor hFcRn.


Author(s):  
Zhidan Li ◽  
Wei Zhang ◽  
Fang Luo ◽  
Jian Li ◽  
Wenbin Yang ◽  
...  

Schistosoma japonicum infection showed protective effects against allergic airway inflammation (AAI). However, controversial findings exist especially regarding the timing of the helminth infection and the underlying mechanisms. Most previous studies focused on understanding the preventive effect of S. japonicum infection on asthma (infection before allergen sensitization), whereas the protective effects of S. japonicum infection (allergen sensitization before infection) on asthma were rarely investigated. In this study, we investigated the protective effects of S. japonicum infection on AAI using a mouse model of OVA-induced asthma. To explore how the timing of S. japonicum infection influences its protective effect, the mice were percutaneously infected with cercaria of S. japonicum at either 1 day (infection at lung-stage during AAI) or 14 days before ovalbumin (OVA) challenge (infection at post–lung-stage during AAI). We found that lung-stage S. japonicum infection significantly ameliorated OVA-induced AAI, whereas post–lung-stage infection did not. Mechanistically, lung-stage S. japonicum infection significantly upregulated the frequency of regulatory T cells (Treg cells), especially OVA-specific Treg cells, in lung tissue, which negatively correlated with the level of OVA-specific immunoglobulin E (IgE). Depletion of Treg cells in vivo partially counteracted the protective effect of lung-stage S. japonicum infection on asthma. Furthermore, transcriptomic analysis of lung tissue showed that lung-stage S. japonicum infection during AAI shaped the microenvironment to favor Treg induction. In conclusion, our data showed that lung-stage S. japonicum infection could relieve OVA-induced asthma in a mouse model. The protective effect was mediated by the upregulated OVA-specific Treg cells, which suppressed IgE production. Our results may facilitate the discovery of a novel therapy for AAI.


Sign in / Sign up

Export Citation Format

Share Document