scholarly journals Quercetin Alleviates the Immunotoxic Impact Mediated by Oxidative Stress and Inflammation Induced by Doxorubicin Expo-Sure in Rats

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1906
Author(s):  
Mayada R. Farag ◽  
Attia A. A. Moselhy ◽  
Amany El-Mleeh ◽  
Samira H. Aljuaydi ◽  
Tamer Ahmed Ismail ◽  
...  
Keyword(s):  
Antioxidant Status ◽  
Fruits And Vegetables ◽  
Caspase 3 ◽  
Chemotherapeutic Agent ◽  
Morphological Changes ◽  
Apoptotic Markers ◽  
Tnf Α ◽  
Chemotherapy Patients ◽  
The Impact ◽  
Cat Gene

Doxorubicin (DOX) is a chemotherapeutic agent against hematogenous and solid tumors with undesirable side effects including immunosuppression. Quercetin (QUR), a natural flavonoid abundant in fruits and vegetables, has a potent antioxidant activity. The aim of the current study was to assess the impact of QUR on DOX-induced hematological and immunological dysfunctions in a rodent model. Randomly grouped rats were treated as follows: control, QUR alone (50 mg/kg for 15 days per os), DOX alone (2.5 mg/kg I/P, three times a week, for two weeks), and co-treated rats with QUR for 15 days prior to and concomitantly with DOX (for two weeks), at the doses intended for groups two and three. DOX alone significantly disrupted the erythrogram and leukogram variables. Serum immunoglobulin (IgG, IgM, and IgE) levels and the activities of catalase (CAT) and superoxide dismutase (SOD) and in spleen were declined. The DNA damage traits in spleen were elevated with an upregulation of the expression of the apoptotic markers (p53 and Caspase-3 genes) and the proinflammatory cytokines (IL-6 and TNF-α genes), while the expression of CAT gene was downregulated. These biochemical changes were accompanied by morphological changes in the spleen of DOX-treated rats. Co-treatment with QUR abated most of the DOX-mediated alterations in hematological variables, serum immunoglobulins, and spleen antioxidant status, pro-inflammatory and apoptotic responses, and histopathological alterations. In essence, these data suggest that QUR alleviated DOX-induced toxicities on the bone marrow, spleen, and antibody-producing cells. Supplementation of chemotherapy patients with QUR could circumvent the DOX-induced inflammation and immunotoxicity, and thus prevent chemotherapy failure.

Smo-Shh signaling activator purmorphamine ameliorates neurobehavioral, molecular, and morphological alterations in an intracerebroventricular propionic acid-induced experimental model of autism

2021 ◽  
pp. 096032712110134
Author(s):  
S Rahi ◽  
R Gupta ◽  
A Sharma ◽  
S Mehan
Keyword(s):  
Propionic Acid ◽  
Developmental Process ◽  
Morphological Changes ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Autism Spectrum ◽  
Neurodevelopmental Disease ◽  
Shh Pathway ◽  
Apoptotic Markers ◽  
The Impact

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disease characterized by cognitive and sensorimotor impairment. Numerous research findings have consistently shown that alteration of Smo-Shh (smoothened-sonic hedgehog) signaling during the developmental process plays a significant role in ASD and triggers neuronal changes by promoting neuroinflammation and apoptotic markers. Purmorphamine (PUR), a small purine-derived agonist of the Smo-Shh pathway, shows resistance to hippocampal neuronal cell oxidation and decreases neuronal cell death. The goal of this study was to investigate the neuroprotective potential of PUR in brain intoxication induced by intracerebroventricular-propionic acid (ICV-PPA) in rats, with a focus on its effect on Smo-Shh regulation in the brain of rats. In addition, we analyze the impact of PUR on myelin basic protein (MBP) and apoptotic markers such as Caspase-3, Bax (pro-apoptotic), and Bcl-2 (anti-apoptotic) in rat brain homogenates. Chronic ICV-PPA infusion was administered consecutively for 11 days to induce autism in rats. In order to investigate behavioral alterations, rats were tested for spatial learning in the Morris Water Maze (MWM), locomotive alterations using actophotometer, and beam crossing task, while Forced Swimming Test (FST) for depressive behavior. PUR treatment with 5 mg/kg and 10 mg/kg (i.p.) was administered from day 12 to 44. Besides cellular, molecular and neuroinflammatory analyses, neurotransmitter levels and oxidative markers have also been studied in brain homogenates. The results of this study have shown that PUR increases the level of Smo-Shh and restores the neurochemical levels, and potentially prevents morphological changes, including demyelination.

Potential role of the NADPH oxidase NOX1 in the pathogenesis of 5-fluorouracil-induced intestinal mucositis in mice

2012 ◽  
Vol 302 (10) ◽  
pp. G1133-G1142 ◽  
Author(s):  
Masashi Yasuda ◽  
Shinichi Kato ◽  
Naoki Yamanaka ◽  
Maho Iimori ◽  
Daichi Utsumi ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Caspase 3 ◽  
Potential Role ◽  
Chemotherapeutic Agent ◽  
Wild Type ◽  
Villus Height ◽  
Tnf Α ◽  
Nadph Oxidase 1 ◽  
Intestinal Mucositis

Although NADPH oxidase 1 (NOX1) has been shown to be highly expressed in the gastrointestinal tract, the physiological and pathophysiological roles of this enzyme are not yet fully understood. In the present study, we investigated the role of NOX1 in the pathogenesis of intestinal mucositis induced by the cancer chemotherapeutic agent 5-fluorouracil (5-FU) in mice. Intestinal mucositis was induced in Nox1 knockout (Nox1KO) and littermate wild-type (WT) mice via single, daily administration of 5-FU for 5 days. In WT mice, 5-FU caused severe intestinal mucositis characterized by a shortening of villus height, a disruption of crypts, a loss of body weight, and diarrhea. In Nox1KO mice, however, the severity of mucositis was significantly reduced, particularly with respect to crypt disruption. The numbers of apoptotic caspase-3- and caspase-8-activated cells in the intestinal crypt increased 24 h after the first 5-FU administration but were overall significantly lower in Nox1KO than in WT mice. Furthermore, the 5-FU-mediated upregulation of TNF-α, IL-1β, and NOX1 and the production of reactive oxygen species were significantly attenuated in Nox1KO mice compared with that in WT mice. These findings suggest that NOX1 plays an important role in the pathogenesis of 5-FU-induced intestinal mucositis. NOX1-derived ROS production following administration of 5-FU may promote the apoptotic response through upregulation of inflammatory cytokines.

scholarly journals Protective Effects of Astragalus Polysaccharide on Sepsis-Induced Acute Kidney Injury

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Jie Sun ◽  
Shanzhai Wei ◽  
Yilai Zhang ◽  
Jia Li
Keyword(s):  
Caspase 3 ◽  
Morphological Changes ◽  
Kidney Injury ◽  
Cell Counting ◽  
Enzyme Linked Immunosorbent Assay ◽  
In Vitro Experiments ◽  
Caspase 9 ◽  
Astragalus Polysaccharide ◽  
Tnf Α

Objective. To explore the protective roles of Astragalus polysaccharide (APS) on acute renal injury (AKI) induced by sepsis. Methods. Firstly, an animal model of sepsis-induced AKI was established by injecting lipopolysaccharide (LPS) into mice. The mice were pretreated with an intraperitoneal injection of 1, 3, and 5 mg/(kg·d) APS for 3 consecutive days. The severity of kidney injury was then scored by histopathological analysis, and the concentrations of serum urea nitrogen (BUN) and serum creatinine (SCr) and the levels of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) were determined as well. In in vitro experiments, lipopolysaccharide (LPS) was used to induce HK-2 cell injury to establish a sepsis-induced AKI cell model, and the cell counting kit-8 (CCK-8) method was performed to determine the cytotoxicity and appropriate experimental concentration of APS. Then, cells were divided into the control, LPS, and APS+LPS groups. Cell apoptosis and inflammation-related TNF-α, IL-1β, IL-6, and IL-8 were determined by flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. The microscope was used to observe the morphological changes of cells, and the cell migration ability was measured by wound healing assay. RT-qPCR and Western blot assay were used to determine the mRNA and protein levels of apoptosis-related factors including caspase-3, caspase-9, Bax, and Bcl-2; endoplasmic reticulum stress- (ERS-) related biomarkers including C/EBP homologous protein (CHOP) and glucose-regulated protein78 (GRP78); and epithelial-mesenchymal transition- (EMT-) related biomarkers including E-cadherin, Snail, α-smooth muscle actin (α-SMΑ), and Vimentin. Results. In vivo experiments in mice showed that APS can reverse LPS-induced kidney damage in a concentration-dependent manner ( P < 0.05 ); the concentrations of BUN and Scr were increased (all P < 0.05 ); similarly, the levels of TNF-α and IL-1β were increased as well (all P < 0.05 ). In in vitro experiments, the results showed that LPS can significantly cause HK-2 cell damage and induce apoptosis, inflammation, ERS, and EMT. When APS concentration was in the range of 0-200 μg/mL, it had no cytotoxicity in HK-2 cells, and 100 μg/mL APS pretreatment could significantly mitigate the decrease of cell activity induced by LPS ( P < 0.05 ). Compared with the LPS group, APS pretreatment could inhibit the expression of inflammatory factors including TNF-α, IL-1 β, IL-6, and IL-8 (all P < 0.05 ), reducing the number of apoptotic cells ( P < 0.05 ), suppressing the expression of caspase-3, caspase-9, and Bax, but upregulating the expression levels of Bcl-2. In ERS, APS pretreatment inhibited LPS-induced upregulation of CHOP and GRP78. Moreover, in EMT, APS pretreatment could inhibit the morphological changes of cells, downregulate the migration, decrease the expression of EMT biomarkers, and inhibit the process of EMT. Conclusion. APS could alleviate sepsis-induced AKI by regulating inflammation, apoptosis, ERS, and EMT.

Anti-inflammatory, anti-oxidant and anti-lipaemic effects of daily dietary coenzyme-Q10 supplement in a mouse model of metabolic syndrome

2021 ◽  
Vol 20 ◽  
Author(s):  
Olakunle J. Onaolapo ◽  
Sarafa A. Omotoso ◽  
Anthony T. Olofinnade ◽  
Adejoke Y. Onaolapo
Keyword(s):  
Metabolic Syndrome ◽  
Lipid Peroxidation ◽  
Mouse Model ◽  
Lipid Profile ◽  
Antioxidant Status ◽  
Management Interventions ◽  
Tnf Α ◽  
Anti Oxidant ◽  
Anti Inflammatory ◽  
The Impact

Background: The dietary model of metabolic syndrome has continued to aid our understanding of its pathogenesis and possible management interventions. However, despite progress in research, therapy continues to be challenging in humans; hence, the search for newer treatment and prevention options. Objective: To evaluate the impact of dietary CQ10 supplementation on metabolic, oxidative and inflammatory markers in a diet-induced mouse model of metabolic syndrome. Methods: Mouse groups were fed standard diet (SD), high-fat high-sugar (HFHS) diet, and SD or HFHS diet (with incorporated CQ10) at 60 and 120 mg/kg of feed respectively. At the completion of the study (8 weeks), blood glucose levels, superoxide dismutase (SOD) activity, plasma insulin, leptin, adiponectin, TNF-α, IL-10, serum lipid profile, and lipid peroxidation (LPO) levels were assessed. The liver was either homogenised for the assessment of antioxidant status or processed for general histology. Results: Dietary CQ10 mitigated HFHS diet-induced weight gain, decreased glucose, insulin and leptin levels; and increased adiponectin levels in mice. Coenzyme-Q10 improved the antioxidant status of the liver and blood in HFHS diet fed mice, while also decreasing lipid peroxidation. Lipid profile improved, level of TNF-α decreased and IL-10 increased following CQ10 diet. A mitigation of HFHS diet-induced alteration in liver morphology was also observed with CQ10. Conclusion: Dietary CQ10 supplementation mitigates HFHS diet-induced changes in mice possibly through its anti-oxidant, anti-lipaemic and anti-inflammatory potential.

scholarly journals Impact of Spatial and Temporal Stability of Aneurismal Flow Vortices on Vascular Endothelial Cells

2021 ◽  
Author(s):  
Kevin Sunderland ◽  
Wenkai Jia ◽  
Weilue He ◽  
Jingfeng Jiang ◽  
Feng Zhao
Keyword(s):  
Cell Adhesion ◽  
Caspase 3 ◽  
Morphological Changes ◽  
Vascular Endothelial Cell ◽  
Temporal Stability ◽  
Vortical Flow ◽  
Vascular Endothelial ◽  
Vortex Stability ◽  
The Impact ◽  
Cell Cell

Disturbed flow vortices are linked with altered vascular endothelial cell (EC) morphology and protein expression indicative of intracranial aneurysms (IA). Unfortunately, lesser known is the impact of vortex spatial and temporal stability on EC changes. In this study, the interplay between vortex stability and EC changes was investigated by a novel combination of parallel plate flow chamber (PPFC) design and computational analysis. ECs were exposed to laminar (7.5 dynes/cm wall shear stress) or low (<1 dynes/cm) stress vortical flow using PPFCs. Immunofluorescent imaging analyzed EC morphology, while ELISA tests quantified VE-cadherin (cell-cell adhesion), VCAM-1 (macrophage-EC adhesion), and cleaved caspase-3 (apoptotic signal) expression. PPFC flow was simulated, then vortex stability calculated via the temporally averaged degree of (volume) overlap (TA-DVO) of vortices within a given area. EC morphological changes were independent of vortex stability. Increased stability promoted VE-cadherin degradation (correlation coefficient r = -0.84) and 5-fold increased cleaved caspase-3 post 24-hrs in stable (TA-DVO 0.736+0.05) vs unstable (TA-DVO 0.606+0.2) vortices. ECs in stable vortices displayed a 4.5-fold increase in VCAM-1 than unstable counterparts after 12-hrs flow. Flow vortices of greater spatial and temporal stability impart greater degrees of EC changes related to inflammation, cell-cell adhesion, and apoptosis, than unstable vortices.

Artemisia Annua Ethanolic Extract Mitigated Small Intestinal Lesions in Hamsters Infected With Giardia Lamblia Possibly Through Modulation of Mucosal Immunity

2020 ◽  
Author(s):  
Tarek Hamdy Abd-Elhamid ◽  
Iman A. M. Abdel-Rahman ◽  
Amany Refaat Mahmoud ◽  
Samer S. Fouad ◽  
Osama H. Abdella ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mucosal Immunity ◽  
Giardia Lamblia ◽  
Caspase 3 ◽  
Artemisia Annua ◽  
Morphological Changes ◽  
Ethanolic Extract ◽  
Intraepithelial Lymphocytes ◽  
Tnf Α ◽  
Small Intestinal

Abstract Giardiasis is a worldwide health problem caused by Giardia lamblia. Unfortunately, G. lamblia developed drug resistance against commonly used therapeutic agents. Artemisia annua (A. annua) derivatives showed therapeutic efficacy against a number of parasitic infestations. Here, we aimed to elucidate the effect of A. annua on giardiasis-induced small intestinal changes in hamsters. Thirty-two hamsters were divided into 4 groups. GI: Uninfected, GII: infected with G. lamblia cysts and untreated, GIII: infected and treated with metronidazole, served as a positive control, and GIV: infected and treated with the A. annua ethanolic extract. The efficacy of the extract was assessed by trophozoite counts, serum cytokine levels and histopathology. Infection of gerbils with G. lamblia cysts significantly decreased serum nitrite, while increased serum IL-6, INF-γ and TNF-α. Additionally, G. lamblia increased intraepithelial lymphocytes (IEL) while reduced villus heights, goblet cell (GC) number and muscularis externa (ME) thickness. Immunohistochemical analysis showed that G. lamblia increased inducible nitric oxide synthase (iNOS) and caspase-3 expression. In contrast, treating infected animals with A. annua significantly reduced the mean trophozoite counts, serum nitrite, IL-6, INF-γ, TNF-α levels and IEL numbers while increased villus heights, GC numbers and ME thickness. Moreover, A. annua reversed giardiasis-induced changes in iNOS and caspase-3 expression. In conclusion; we showed clearly that A. annua extract reduced the severity and morphological changes of giardiasis possibly through modulation of nitric oxide production and mucosal immunity. These effects were comparable to effects of metronidazole. Therefore, we assume that A. annua extracts could be used as adjuvant therapy during treatment of giardiasis.

scholarly journals ADP and Other Metabolites Released from Acanthamoeba castellanii Lead to Human Monocytic Cell Death through Apoptosis and Stimulate the Secretion of Proinflammatory Cytokines

2002 ◽  
Vol 70 (8) ◽  
pp. 4424-4432 ◽  
Author(s):  
A. Mattana ◽  
V. Cappai ◽  
L. Alberti ◽  
C. Serra ◽  
P. L. Fiori ◽  
...  
Keyword(s):  
Cell Death ◽  
Proinflammatory Cytokines ◽  
Caspase 3 ◽  
Morphological Changes ◽  
Cell Damage ◽  
Acanthamoeba Castellanii ◽  
Monocytic Cell ◽  
Tnf Α ◽  
Human Monocytic Cell ◽  
Molecular Masses

ABSTRACT Monocytes/macrophages are thought to be involved in Acanthamoeba infections. The aim of this work was to study whether soluble metabolites (ADP and other compounds) released by Acanthamoeba castellanii trophozoites could induce morphological and biochemical changes in human monocytic cells in vitro. We demonstrate here that ADP constitutively released in the medium by A. castellanii, interacting with specific P2y2 purinoceptors expressed on the monocytic cell membrane, caused a biphasic rise in [Ca2+]i, morphological changes characteristics of cells undergoing apoptosis, caspase-3 activation, and secretion of tumor necrosis factor alpha (TNF-α). The same results were found in monocytes exposed to purified ADP. Cell damage and TNF-α release induced by amoebic ADP were blocked by the P2y2 inhibitor suramin. Other metabolites contained in amoebic cell-free supernatants, with molecular masses of, respectively, >30 kDa and between 30 and 10 kDa, also caused morphological modifications and activation of intracellular caspase-3, characteristics of programmed cell death. Nevertheless, mechanisms by which these molecules trigger cell damage appeared to differ from that of ADP. In addition, other amoebic thermolable metabolites with molecular masses of <10 kDa caused the secretion of interleukin-1β. These findings suggest that pathogenic free-living A. castellanii by release of ADP and other metabolites lead to human monocytic cell death through apoptosis and stimulate the secretion of proinflammatory cytokines.

scholarly journals The Effects And Possible Mechanisms of Vortioxetine on Pentylenetetrazole-Induced Seizures In Rats

2021 ◽  
Author(s):  
Ahmet Sevki Taskiran ◽  
Ahmet Kemal Filiz
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Memory Impairment ◽  
Caspase 3 ◽  
Epileptic Seizures ◽  
Guanosine Monophosphate ◽  
Control Group ◽  
Caspase 9 ◽  
Tnf Α ◽  
The Impact

Abstract Antidepressants are known to demonstrate various effects on the nervous system. As a new antidepressant, vortioxetine is used for major depression in adult patients, with no clear indication of epileptic seizures. Therefore, the aim here was to examine the impact of vortioxetine on pentylenetetrazole-induced epileptic seizures in rats. The rats were randomly divided into 5 groups, each with 6 rats. Group 1 was control, Group 2 was administered saline (1 mL/kg/day serum physiologic), Group 3 was given (1 mg/kg/day diazepam), and Groups 4 and 5 were administered vortioxetine (2.5 and 5 mg/kg/day). The experimental groups (Groups 2-5) were given the drugs for a total of 7 days. Pentylenetetrazole (45 mg/kg) was administered on day 7 to all but the control group. Behavioral testing was performed using the passive avoidance and open field tasks. Total antioxidant status (TAS), total oxidant status (TOS), tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1 β), neuronal nitric oxide synthase (nNOS), nitric oxide (NO), soluble guanylate cyclase (sGC), cyclic guanosine monophosphate (cGMP) caspase-3, and caspase-9 levels were measured using a commercial kit. The groups receiving vortioxetine (2.5 mg/kg and 5 mg/kg) were found to have delayed epileptic seizure onset times and reduced seizure stages with improved memory impairment after seizures. These groups also had increased TAS levels and decreased TOS levels in the cortex and hippocampus. Additionally, TNF-α, IL-1 β, nNOS, sGC, cGMP, caspase-3, and caspase-9 levels in the cortex and hippocampus were statistically significantly lower for these groups. Vortioxetine was determined to have protective effects on pentylenetetrazole-induced seizures in rats, with alleviated seizures and improved memory impairment, oxidative stress, inflammation, and apoptosis. The mechanisms of vortioxetine may involve the inhibition of oxidative stress, inflammation, and the nNOS/sGC/cGMP signalling pathway.

The impact of increased consumption of fruits and vegetables on cortisol and cortisone excretion in 24-h urine of children

2015 ◽  
Vol 122 (03) ◽  
Author(s):  
J Esche ◽  
L Shi ◽  
A Sánchez-Guijo ◽  
MF Hartmann ◽  
S Wudy ◽  
...  
Keyword(s):  
Fruits And Vegetables ◽  
The Impact

Comparative assessment of morphological mechanisms of maintaining structural liver homeostasis in the dynamics of exposure to coal-rock dust and sodium fluoride on the body

2020 ◽  
pp. 189-194
Author(s):  
M. S. Bugaeva ◽  
O. I. Bondarev ◽  
N. N. Mikhailova ◽  
L. G. Gorokhova
Keyword(s):  
Sodium Fluoride ◽  
Morphological Changes ◽  
The Body ◽  
System Level ◽  
Production Factor ◽  
Coal Rock ◽  
The Impact ◽  
Structural Homeostasis ◽  
Rock Dust

Introduction. The impact on the body of such factors of the production environment as coal-rock dust and fluorine compounds leads to certain shift s in strict indicators of homeostasis at the system level. Maintaining the relative constancy of the internal environment of the body is provided by the functional consistency of all organs and systems, the leading of which is the liver. Organ repair plays a crucial role in restoring the structure of genetic material and maintaining normal cell viability. When this mechanism is damaged, the compensatory capabilities of the organ are disrupted, homeostasis is disrupted at the cellular and organizational levels, and the development of the main pathological processes is noted.The aim of the study is to compare the morphological mechanisms of maintaining structural homeostasis of the liver in the dynamics of the impact on the body of coal-rock dust and sodium fluoride.Materials and methods. Experimental studies were conducted on adult white male laboratory rats. Features of morphological mechanisms for maintaining structural homeostasis of the liver in the dynamics of exposure to coal-rock dust and sodium fluoride were studied on experimental models of pneumoconiosis and fluoride intoxication. For histological examination in experimental animals, liver sampling was performed after 1, 3, 6, 9, 12 weeks of the experiment.Results. The specificity of morphological changes in the liver depending on the harmful production factor was revealed. It is shown that chronic exposure to coal-rock dust and sodium fluoride is characterized by the development of similar morphological changes in the liver and its vessels from the predominance of the initial compensatory-adaptive to pronounced violations of the stromal and parenchymal components. Long-term inhalation of coal-rock dust at 1–3 weeks of seeding triggers adaptive mechanisms in the liver in the form of increased functional activity of cells, formation of double-core hepatocytes, activation of immunocompetent cells and endotheliocytes, ensuring the preservation of the parenchyma and the general morphostructure of the organ until the 12th week of the experiment. Exposure to sodium fluoride leads to early disruption of liver compensatory mechanisms and the development of dystrophic changes in the parenchyma with the formation of necrosis foci as early as the 6th week of the experiment.Conclusions. The study of mechanisms for compensating the liver structure in conditions of long-term exposure to coal-rock dust and sodium fluoride, as well as processes that indicate their failure, and the timing of their occurrence, is of theoretical and practical importance for developing recommendations for the timely prevention and correction of pathological conditions developing in employees of the aluminum and coal industry.The authors declare no conflict of interests.

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