Effects of aluminum oxide (Al2O3) nanoparticles on ECG, myocardial inflammatory cytokines, redox state, and connexin 43 and lipid profile in rats: possible cardioprotective effect of gallic acid

2016 ◽  
Vol 94 (8) ◽  
pp. 868-878 ◽  
Author(s):  
El-Hussainy M.A. El-Hussainy ◽  
Abdelaziz M. Hussein ◽  
Azza Abdel-Aziz ◽  
Ibrahim El-Mehasseb
Keyword(s):  
Aluminum Oxide ◽  
Gallic Acid ◽  
Connexin 43 ◽  
Redox State ◽  
Chronic Administration ◽  
Albino Rats ◽  
Al2o3 Nanoparticles ◽  
Cx43 Expression ◽  
Tnf Α ◽  
Nano Alumina

The objectives of present study were to examine the effects of aluminum oxide (Al2O3) nanoparticles on myocardial functions, electrical activities, morphology, inflammation, redox state, and myocardial expression of connexin 43 (Cx43) and the effect of gallic acid (GA) on these effects in a rat animal model. Forty male albino rats were divided into 4 equal groups: the control (normal) group; the Al2O3group, rats received Al2O3(30 mg·kg–1, i.p.) daily for 14 days; the nano-alumina group, rats received nano-alumina (30 mg·kg–1, i.p.) daily for 14 days; and the nano-alumina + GA group, rats received GA (100 mg·kg–1orally once daily) for 14 days before nano-alumina administration. The results showed disturbed ECG variables and significant increases in serum levels of LDH, creatine phosphokinase (CPK), CK-MB, triglycerides (TGs), cholesterol and LDL, nitric oxide (NO), and TNF-α and myocardial concentrations of NO, TNF-α, and malondialdehyde (MDA), with significant decreases in serum HDL and myocardial GSH, SOD, catalase (CAT), and Cx43 expression in the nano-alumina group. Pretreatment with GA improved significantly all parameters except serum and myocardial NO. We concluded that chronic administration of Al2O3NPs caused myocardial dysfunctions, and pretreatment with GA ameliorates myocardial injury induced by nano-alumina, probably through its hypolipidaemic, anti-inflammatory, and antioxidant effects and upregulation of Cx43 in heart.

Phosphorylation of connexin 43 induced by traumatic brain injury promotes exosome release

2018 ◽  
Vol 119 (1) ◽  
pp. 305-311 ◽  
Author(s):  
Wei Chen ◽  
Yijun Guo ◽  
Wenjin Yang ◽  
Lei Chen ◽  
Dabin Ren ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Gap Junction ◽  
Connexin 43 ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Cx43 Expression ◽  
Term Potentiation ◽  
Junction Protein

Traumatic brain injury (TBI) caused by the external force leads to the neuronal dysfunction and even death. TBI has been reported to significantly increase the phosphorylation of glial gap junction protein connexin 43 (Cx43), which in turn propagates damages into surrounding brain tissues. However, the neuroprotective and anti-apoptosis effects of glia-derived exosomes have also been implicated in recent studies. Therefore, we detected whether TBI-induced phosphorylation of Cx43 would promote exosome release in rat brain. To generate TBI model, adult male Sprague-Dawley rats were subjected to lateral fluid percussion injury. Phosphorylated Cx43 protein levels and exosome activities were quantified using Western blot analysis following TBI. Long-term potentiation (LTP) was also tested in rat hippocampal slices. TBI significantly increased the phosphorylated Cx43 and exosome markers expression in rat ipsilateral hippocampus, but not cortex. Blocking the activity of Cx43 or ERK, but not JNK, significantly suppressed TBI-induced exosome release in hippocampus. Furthermore, TBI significantly inhibited the induction of LTP in hippocampal slices, which could be partially but significantly restored by pretreatment with exosomes. The results imply that TBI-activated Cx43 could mediate a nociceptive effect by propagating the brain damages, as well as a neuroprotective effect by promoting exosome release. NEW & NOTEWORTHY We have demonstrated in rat traumatic brain injury (TBI) models that both phosphorylated connexin 43 (p-Cx43) expression and exosome release were elevated in the hippocampus following TBI. The promoted exosome release depends on the phosphorylation of Cx43 and requires ERK signaling activation. Exosome treatment could partially restore the attenuated long-term potentiation. Our results provide new insight for future therapeutic direction on the functional recovery of TBI by promoting p-Cx43-dependent exosome release but limiting the gap junction-mediated bystander effect.

DOSE-DEPENDENT CHARACTER OF DISTURBANCE OF HEMATOPOIETIC AND IMMUNE SYSTEMS FUNCTION, PRODUCTION OF SOME HORMONES IN EXPERIMENTAL URANIUM ACETATE DIHYDRATE EXPOSURE

2021 ◽  
Vol 1 (1) ◽  
pp. 14-19
Author(s):  
Е. G. Trapeznikova ◽  
V. В. Popov ◽  
A. S. Radilov ◽  
V. V. Shilov
Keyword(s):  
Hematological Parameters ◽  
Chronic Administration ◽  
Absolute Number ◽  
Uranyl Acetate ◽  
The Body ◽  
Acetate Dihydrate ◽  
Functional Changes ◽  
Cd8 Cells ◽  
Tnf Α ◽  
Dose Dependent

The paper presents the results of an experimental study of the dose-dependent nature of functional changes in the body systems under chronic administration of uranyl acetate dihydrate in doses of 0.5 and 5.0 mg/kg per element for 18 weeks. The study was performed on 45 male outbred rats. It has been shown that uranyl acetate dihydrate in a dose of 0.5 mg/kg had no significant effect on hematological parameters. At the same time, activation of bactericidal activity of neutrophils, a decrease in the immunoregulatory index, and an increase in the blood concentration of tumor necrosis factor (TNF-α) have been revealed. The toxicant administered to rats in a dose of 5 mg/kg led to a decrease in the absolute number of erythrocytes, hemoglobin, hematocrit, platelets, the release of myelocytes into the blood, basophilia, monocytosis, the appearance of leukolysis cells and plasmatization of lymphocytes. On the part of the immune system, an increase in the biocidal capacity of neutrophilic granulocytes, TNF-α production, an increase in the number of CD8+ cells, and a reduction in the CD4+/CD8+ ratio have been found. Uranyl acetate dihydrate had a dose-dependent effect only on the number of cytotoxic T-lymphocytes, T-cells with the CD4+CD8+ phenotype, on the immunoregulatory index, and on the level of TNF-α. Hyperglycemia and glucosuria were also dose-dependent. An increase in glucose in the blood and urine indicated a violation of carbohydrate metabolism and kidney function. There was a decrease in the concentration of thyroxine, testosterone and an increase in the level of insulin. Uranyl acetate dihydrate led to the development of insulin resistance. The level of hormones did not depend on the dose of the toxicant administered to the animals.

Antioxidant, anti-inflammatory, and anti-apoptotic effects of zinc supplementation in testes of rats with experimentally induced diabetes

2018 ◽  
Vol 43 (10) ◽  
pp. 1010-1018 ◽  
Author(s):  
Neven M. Aziz ◽  
Maha Y. Kamel ◽  
Manar S. Mohamed ◽  
Sabreen M. Ahmed
Keyword(s):  
Connexin 43 ◽  
Concomitant Administration ◽  
Serum Levels ◽  
Diabetic Rats ◽  
Control Group ◽  
Albino Rats ◽  
Safe Alternative ◽  
Once Daily ◽  
Factor Α ◽  
Percent Area

One of the major obstacles that males with diabetes may confront is subfertility or infertility. Thus, the present study investigated the effect of co-administration of metformin and zinc (Zn) on the testes of streptozotocin-induced diabetic rats. Male albino rats were randomly divided into 4 groups: control group; untreated diabetic group; diabetic + metformin group, in which diabetic rats were treated orally with metformin (250 mg/kg) once daily for 4 weeks; and diabetic + metformin + Zn group, in which diabetic rats were treated orally with metformin in combination with Zn (10 mg/kg) once daily for 4 weeks. Concomitant administration of metformin and Zn produced a significant decrease in serum levels of glucose and insulin and testicular levels of malondialdehyde and tumor necrosis factor α. Additionally, there was a significant increase in serum levels of Zn, testosterone, and follicle-stimulating hormone, as well as testicular total antioxidant capacity and anti-apoptotic protein Bcl-2, when compared with both the diabetic and metformin-treated diabetic groups. Moreover, co-administration of Zn and metformin significantly improved testicular histopathology, with a significant reduction in percent area of collagen fibers and nuclear factor kappa B (p65) immunoreactivity and a significant increase in seminiferous tubule diameter and connexin 43 immunoreactivity as compared with the diabetic and metformin-treated diabetic groups. In conclusion, the combination of Zn and metformin was an efficacious and safe alternative treatment, as it had superior antihyperglycemic efficacy and provided additional benefits over metformin alone in rats with type 2 diabetes.

Effects of ferulic acid on oxidative stress, heat shock protein 70, connexin 43, and monoamines in the hippocampus of pentylenetetrazole-kindled rats

2017 ◽  
Vol 95 (6) ◽  
pp. 732-742 ◽  
Author(s):  
Abdelaziz M. Hussein ◽  
Khaled M. Abbas ◽  
Osama A. Abulseoud ◽  
El-Hussainy M.A. El-Hussainy
Keyword(s):  
Oxidative Stress ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Ferulic Acid ◽  
Group Treatment ◽  
Heat Shock Protein 70 ◽  
Connexin 43 ◽  
Hsp70 Expression ◽  
Neuroprotective Effects ◽  
Cx43 Expression

The present study investigated the effects of ferulic acid (FA) on pentylenetetrazole (PTZ)-induced seizures, oxidative stress markers (malondialdehyde (MDA), catalase, and reduced glutathione (GSH)), connexin (Cx) 43, heat shock protein 70 (Hsp 70), and monoamines (serotonin (5-HT) and norepinephrine (NE)) levels in a rat model of PTZ-induced kindling. Sixty Sprague Dawley rats were divided into 5 equal groups: (a) normal group; (b) FA group: normal rats received FA at a dose of 40 mg/kg daily; (c) PTZ group: normal rats received PTZ at a dose of 50 mg/kg i.p. on alternate days for 15 days; (d) FA-before group: treatment was the same as for the PTZ group, except rats received FA; and (e) FA-after group: rats received FA from sixth dose of PTZ. PTZ caused a significant increase in MDA, Cx43, and Hsp70 along with a significant decrease in GSH, 5-HT, and NE levels and CAT activity in the hippocampus (p < 0.05). Pre- and post-treatment with FA caused significant improvement in behavioral parameters, MDA, CAT, GSH, 5-HT, NE, Cx43 expression, and Hsp70 expression in the hippocampal region (p < 0.05). We conclude that FA has neuroprotective effects in PTZ-induced epilepsy, which might be due to attenuation of oxidative stress and Cx43 expression and upregulation of neuroprotective Hsp70 and neurotransmitters (5-HT and NE).

scholarly journals Transforming growth factor-β1 up-regulates connexin43 expression in osteocytes via canonical Smad-dependent signaling pathway

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Wenjing Liu ◽  
Yujia Cui ◽  
Jianxun Sun ◽  
Linyi Cai ◽  
Jing Xie ◽  
...  
Keyword(s):  
Growth Factor ◽  
Connexin 43 ◽  
Transforming Growth Factor ◽  
Bone Cells ◽  
Underlying Mechanism ◽  
Transforming Growth Factor Β1 ◽  
Type I ◽  
Gap Junctional Intercellular Communication ◽  
Cx43 Expression ◽  
Tgf Β1

Connexin 43 (Cx43)-mediated gap junctional intercellular communication (GJIC) has been shown to be important in regulating multiple functions of bone cells. Transforming growth factor-β1 (TGF-β1) exhibited controversial effects on the expression of Cx43 in different cell types. To date, the effect of TGF-β1 on the Cx43 expression of osteocytes is still unknown. In the present study, we detected the expression of TGF-β1 in osteocytes and bone tissue, and then used recombinant mouse TGF-β1 to elucidate its effect on gap junctions (GJs) of osteocytes. Our data indicated that TGF-β1 up-regulated both mRNA and protein expression of Cx43 in osteocytes. Together with down-regulation of Cx43 expression after being treated with TGF-β type I receptor inhibitor Repsox, we deduced that TGF-β1 can positively regulate Cx43 expression in osteocytes. Thus we next focussed on the downstream signals of TGF-β and found that TGF-β1-mediated smads, Smad3 and Smad4, to translocate into nucleus. These translocated signal proteins bind to the promoter of Gja1 which was responsible for the changed expression of Cx43. The present study provides evidence that TGF-β1 can enhance GJIC between osteocytes through up-regulating Cx43 expression and the underlying mechanism involved in the activation of Smad-dependent pathway.

scholarly journals Ameliorative effect of Aerva lanata against nephrolithiasis following chronic administration of Ethylene glycol in male wistar Albino rats

2021 ◽  
Author(s):  
Ankul Singh S ◽  
Gowri K ◽  
Chitra V
Keyword(s):  
Ethylene Glycol ◽  
Urine Volume ◽  
Chronic Administration ◽  
Negative Control ◽  
Albino Rats ◽  
Standard Group ◽  
Alcoholic Extract ◽  
Health Crisis ◽  
Group I ◽  
Wistar Albino Rats

Abstract Nephrolithiasis appear to be a major health crisis among the population with serious medical related consequences throughout the lifetime of patient. The aim of the study was to evaluate the preventive effect of the hydro-alcoholic extract of A. lanata roots on Urolithiasis rats. Thirty adults male wistar Albino rats weighing 200 – 250 g were divided into five groups comprising 6 rats in each. Group I Served as positive control with water ad libitum. Group II as negative control which is disease treated group receiving 0.75% ethylene glycol mixed with drinking water for 28 days. Group III chosen as standard group receiving ethylene glycol for first 14 days and Cystone 750 mg/Kg from day 15 till day 28. Group IV and V received ethylene glycol for first 14 days and treatment regimen of LD (400 mg/Kg) and HD 800 mg/Kg orally from day 15 till day 28. Invitro studies like Nucleation, Aggregation and Growth assays were performed. Urine volume and pH was collected and observed for change in appearance, pH, odour and turbidity. Extract was given by preparing suspension and stability was observed by measuring its parameters. On Day 29, the kidneys were dissected and histopathology was done to check tubular injury. There was Increase in urine volume, enhanced excretion of urinary constituents like citrate, oxalate etc. and improving clearance rate. Improvement in pH and antioxidant activity was observed in treated groups. The extract showed that it has prominent effect on nephrolithiasis and has better safety profile in the dose given.

CX43 expression, phosphorylation, and distribution in the normal and autoimmune orchitic testis with a look at gap junctions joining germ cell to germ cell

2011 ◽  
Vol 300 (1) ◽  
pp. R121-R139 ◽  
Author(s):  
R.-Marc Pelletier ◽  
Casimir D. Akpovi ◽  
Li Chen ◽  
Robert Day ◽  
María L. Vitale
Keyword(s):  
Cell Differentiation ◽  
Gap Junctions ◽  
Germ Cell ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Seminiferous Tubule ◽  
Connexin 43 ◽  
Cx43 Expression ◽  
Cx43 Protein ◽  
Cx43 Mrna

Spermatogenesis requires connexin 43 (Cx43).This study examines normal gene transcription, translation, and phosphorylation of Cx43 to define its role on germ cell growth and Sertoli cell's differentiation, and identifies abnormalities arising from spontaneous autoimmune orchitis (AIO) in mink, a seasonal breeder and a natural model for autoimmunity. Northern blot analysis detected 2.8- and a 3.7-kb Cx43 mRNA bands in seminiferous tubule-enriched fractions. Cx43 mRNA increased in seminiferous tubule-enriched fractions throughout development and then seasonally with the completion of spermatogenesis. Cx43 protein levels increased transiently during the colonization of the tubules by the early-stage spermatocytes. Cx43 phosphorylated (PCx43) and nonphosphorylated (NPCx43) in Ser368 decreased during the periods of completion of meiosis and Sertoli cell differentiation, while Cx43 mRNA remained elevated throughout. PCx43 labeled chiefly the plasma membrane except by stage VII when vesicles were also labeled in Sertoli cells. Vesicles and lysosomes in Sertoli cells and the Golgi apparatus in the round spermatids were NPCx43 positive. A decrease in Cx43 gene expression was matched by a Cx43 protein increase in the early, not the late, phase of AIO. Total Cx43 and PCx43 decreased with the advance of orchitis. The study makes a novel finding of gap junctions connecting germ cells. The data indicate that Cx43 protein expression and phosphorylation in Ser368 are stage-specific events that may locally influence the acquisition of meiotic competence and the Sertoli cell differentiation in normal testis. AIO modifies Cx43 levels, suggesting changes in Cx43-mediated intercommunication and spermatogenic activity in response to cytokines imbalances in Sertoli cells.

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