Hydrogen-rich saline attenuates radiation-induced male germ cell loss in mice through reducing hydroxyl radicals

2012 ◽  
Vol 442 (1) ◽  
pp. 49-56 ◽  
Author(s):  
Yunhai Chuai ◽  
Fu Gao ◽  
Bailong Li ◽  
Luqian Zhao ◽  
Liren Qian ◽  
...  
Keyword(s):  
Side Effects ◽  
Hydroxyl Radicals ◽  
Germ Cells ◽  
Morphological Changes ◽  
Sperm Quality ◽  
Cell Loss ◽  
Testicular Tissue ◽  
Protective Role ◽  
Protein Carbonyl

Our recent studies suggest that H2 (hydrogen) has a potential as a novel radioprotector without known toxic side effects. The present study was designed to examine the underlying radioprotective mechanism of H2 and its protective role on irradiated germ cells. Produced by the Fenton reaction and radiolysis of H2O, hydroxyl radicals (•OH) were identified as the free radical species that were reduced by H2. We used a H2 microelectrode to dynamically detect H2 concentration in vivo, and found H2 significantly reduced in situ fluorescence intensity of hydroxyphenyl fluorescein; however, as we treated the mice with H2 after irradiation, the decrease is not significant. We found that pre-treatment of H2 to IR (ionizing radiation) significantly suppressed the reaction of •OH and the cellular macromolecules which caused lipid peroxidation, protein carbonyl and oxidatively damaged DNA. The radioprotective effect of H2 on male germ cells was supported by ameliorated apoptotic findings examined by morphological changes and TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling) in testicular tissue, and by preserved viability of stem spermatogonia examined for testicular histological parameters, daily sperm production and sperm quality; we used WR-2721 [S-2-(3-aminopropylamino)ethyl phosphorothioic acid] as a reference compound. Our results represent the first in vivo evidence in support of a radioprotective role of H2 by neutralizing •OH in irradiated tissue with no side effects.

Mancozeb induces testicular dysfunction through oxidative stress and apoptosis: Protective role of N-acetylcysteine antioxidant

2018 ◽  
Vol 34 (11) ◽  
pp. 798-811 ◽  
Author(s):  
Mohaddeseh Mohammadi-Sardoo ◽  
Ali Mandegary ◽  
Mohammad Nabiuni ◽  
Seyed-Noureddin Nematollahi-Mahani ◽  
Bagher Amirheidari
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Reproductive System ◽  
Histopathological Examination ◽  
Antioxidant Property ◽  
Testicular Tissue ◽  
Protective Role ◽  
Protein Carbonyl ◽  
Mrna Levels ◽  
Nadph Oxidase 4

Mancozeb (MZB) is one of the fungicides used in pest control programs that might affect human health including reproductive system. The aim of this study was to demonstrate the mechanisms through which MZB induces testicular tissue damage and the probable protective effect of N-acetylcysteine (NAC), a modified amino acid, with antioxidant property, against MZB toxicity in an animal model. Male albino mice ( n = 8) were exposed to different doses of MZB (250 and 500 mg/kg/day) by oral gavage without or with NAC (200 mg/kg, twice/week) for 40 days. Sub-chronic MZB dose-dependently decreased sperm motility and count. Exposure to MZB increased lipid peroxidation and protein carbonyl, while it reduced antioxidant enzymes activities, total antioxidant capacity, and glutathione content. The histopathological examination clearly showed deleterious changes in the testicular structure. At the molecular levels, the results of quantitative real time-poly chain reaction (qRT-PCR) showed that MZB upregulated oxidative stress markers inducible nitric oxide synthase (iNOS) and NADPH oxidase 4 (NOX4) and downregulated expression of the glutathione peroxidase 1 (Gpx1) gene as one of the most important antioxidant enzymes. MZB also induced apoptosis dose-dependently in the testes as determined by the terminal dUTP nick-end labeling assay and immunoblotting. NAC administration decreased the mRNA levels of both iNOS and NOX4 with a concomitant increase in Gpx1 expression. It also significantly decreased MZB-induced oxidative stress and apoptosis. Collectively, the present study showed MZB-induced oxidative damage in testes leading to apoptosis. It revealed that antioxidants such as NAC can mitigate oxidant injury induced by the dithiocarbamate pesticides in the reproductive system.

scholarly journals Protection against Doxorubicin-Induced Cytotoxicity by Geniposide Involves AMPKα Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Yan-Yan Meng ◽  
Yu-Pei Yuan ◽  
Xin Zhang ◽  
Chun-Yan Kong ◽  
Peng Song ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Therapeutic Potential ◽  
Cell Loss ◽  
Protective Role ◽  
Protective Effects ◽  
Morphological Examination ◽  
Heart Injury ◽  
Amp Activated Protein Kinase

Oxidative stress and cardiomyocyte apoptosis play critical roles in the development of doxorubicin- (DOX-) induced cardiotoxicity. Our previous study found that geniposide (GE) could inhibit cardiac oxidative stress and apoptosis of cardiomyocytes but its role in DOX-induced heart injury remains unknown. Our study is aimed at investigating whether GE could protect against DOX-induced heart injury. The mice were subjected to a single intraperitoneal injection of DOX (15 mg/kg) to induce cardiomyopathy model. To explore the protective effects, GE was orally given for 10 days. The morphological examination and biochemical analysis were used to evaluate the effects of GE. H9C2 cells were used to verify the protective role of GE in vitro. GE treatment alleviated heart dysfunction and attenuated cardiac oxidative stress and cell loss induced by DOX in vivo and in vitro. GE could activate AMP-activated protein kinase α (AMPKα) in vivo and in vitro. Moreover, inhibition of AMPKα could abolish the protective effects of GE against DOX-induced oxidative stress and apoptosis. GE could protect against DOX-induced heart injury via activation of AMPKα. GE has therapeutic potential for the treatment of DOX cardiotoxicity.

scholarly journals Antigiardial Effect of Kramecyne in Experimental Giardiasis

2017 ◽  
Vol 2017 ◽  
pp. 1-7
Author(s):  
Leticia Eligio-García ◽  
Elida Pontifez-Pablo ◽  
Salúd Pérez-Gutiérrez ◽  
Enedina Jiménez-Cardoso
Keyword(s):  
Side Effects ◽  
High Efficiency ◽  
Morphological Changes ◽  
Lethal Dose ◽  
Expression Of Genes ◽  
Antigiardial Activity ◽  
Resistant Strains ◽  
Polymerase Chain

A variety of drugs are used in giardiasis treatment with different levels of efficiency, presence of side effects, and even formation of resistant strains, so that it is important to search new only-one-dose treatments with high efficiency and less side effects. Kramecyne, an anti-inflammatory compound isolated from methanolic extract ofKrameria cytisoides, does not present toxicity, even at doses of 5,000 mg/kg. The objective was to determine the antigiardial effect of kramecyne overGiardia intestinalis in vitroandin vivoand analyze the expression of genes ERK1, ERK2, and AK on kramecyne treated trophozoites by Real Time Polymerase Chain Reaction (RTPCR). The median lethal dose (LD50) was 40 μg/mL and no morphological changes were observed by staining with blue trypan and light microscopy; experimental gerbil infection was eliminated with 320 μg/Kg of weight. After treatment there were no differences between intestines from treated and untreated gerbils. Kramecyne did not have significant effect over ERK1 and AK, but there are differences in ERK2 expression (p=0.04). Results show antigiardial activity of kramecyne; however the mode of action is still unclear and the evaluation of ultrastructural damage and expressed proteins is an alternative of study to understand the action mechanism.

scholarly journals Stage-specific control of oligodendrocyte survival and morphogenesis by TDP-43

2021 ◽  
Author(s):  
Dongeun Heo ◽  
Jonathan P Ling ◽  
Gian C Molina-Castro ◽  
Abraham J Langseth ◽  
Ari Waisman ◽  
...  
Keyword(s):  
Rna Binding ◽  
Morphological Changes ◽  
Cell Loss ◽  
Adult Brain ◽  
Transcriptional Analysis ◽  
Myelin Sheaths ◽  
Conditional Deletion ◽  
Oligodendrocyte Precursor ◽  
Specific Control

Generation of oligodendrocytes in the adult brain enables both adaptive changes in neural circuits and regeneration of myelin sheaths destroyed by injury, disease, and normal aging. This transformation of oligodendrocyte precursor cells (OPCs) into myelinating oligodendrocytes requires processing of distinct mRNAs at different stages of cell maturation. Although mislocalization and aggregation of the RNA binding protein TDP-43 occur in both neurons and glia in neurodegenerative diseases, the consequences of TDP-43 loss within different stages of the oligodendrocyte lineage are not well understood. By performing stage-specific genetic inactivation of Tardbpin vivo, we show that oligodendrocyte lineage cells are differentially sensitive to loss of TDP-43. While OPCs depend on TDP-43 for survival, with conditional deletion resulting in cascading cell loss followed by rapid regeneration to restore their density, oligodendrocytes become less sensitive to TDP-43 depletion as they mature. Deletion of TDP-43 early in the maturation process led to eventual oligodendrocyte degeneration, seizures and premature lethality, while oligodendrocytes that experienced late deletion survived and mice exhibited a normal lifespan. At both stages, TDP-43 deficient oligodendrocytes formed fewer and thinner myelin sheaths and extended new processes that inappropriately wrapped neuronal somata and blood vessels. Transcriptional analysis revealed that in the absence of TDP-43, key proteins involved in oligodendrocyte maturation and myelination were misspliced leading to aberrant incorporation of cryptic exons. Inducible deletion of TDP-43 from oligodendrocytes in the adult CNS induced the same progressive morphological changes and mice acquired profound hindlimb weakness, suggesting that loss of TDP-43 function in oligodendrocytes may contribute to neuronal dysfunction in neurodegenerative disease.

scholarly journals The insulin sensitiser metformin regulates chicken Sertoli and germ cell populations

Reproduction ◽  
2016 ◽  
Vol 151 (5) ◽  
pp. 527-538 ◽  
Author(s):  
M Faure ◽  
E Guibert ◽  
S Alves ◽  
B Pain ◽  
C Ramé ◽  
...  
Keyword(s):  
Germ Cells ◽  
Sertoli Cells ◽  
Energy Content ◽  
Morphological Changes ◽  
Seminiferous Tubules ◽  
Reduce Food Intake ◽  
Testicular Weight

Abstract Metformin, an insulin sensitiser from the biguanide family of molecules, is used for the treatment of insulin resistance in type 2 diabetes individuals. It increases peripheral glucose uptake and may reduce food intake. Based on the tight link between metabolism and fertility, we investigated the role of metformin on testicular function using in vitro culture of Sertoli cells and seminiferous tubules, complemented by in vivo data obtained following metformin administration to prepubertal chickens. In vitro, metformin treatment reduced Sertoli cell proliferation without inducing apoptosis and morphological changes. The metabolism of Sertoli cells was affected because lactate secretion by Sertoli cells increased approximately twofold and intracellular free ATP was negatively impacted. Two important pathways regulating proliferation and metabolism in Sertoli cells were assayed. Metformin exposure was not associated with an increased phosphorylation of AKT or ERK. There was a 90% reduction in the proportion of proliferating germ cells after a 96-h exposure of seminiferous tubule cultures to metformin. In vivo, 6-week-old chickens treated with metformin for 3 weeks exhibited reduced testicular weight and a 50% decrease in testosterone levels. The expression of a marker of undifferentiated germ cells was unchanged in contrast to the decrease in expression of ‘protamine’, a marker of differentiated germ cells. In conclusion, these results suggest that metformin affects the testicular energy content and the proliferative ability of Sertoli and germ cells. Reproduction (2016) 151 527–538

scholarly journals Dapagliflozin Mediates Plin5/PPARα Signaling Axis to Attenuate Cardiac Hypertrophy

2021 ◽  
Vol 12 ◽  
Author(s):  
Jing Yu ◽  
Huanhuan Zhao ◽  
Xin Qi ◽  
Liping Wei ◽  
Zihao Li ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Cardiac Function ◽  
Protective Effect ◽  
Morphological Changes ◽  
Protective Role ◽  
Cardiomyocyte Hypertrophy ◽  
Signal Pathways ◽  
Signaling Axis

Objective: The purpose of this study was to investigate the effect of dapagliflozin (DAPA), a sodium-glucose cotransporter 2 inhibitor, on relieving cardiac hypertrophy and its potential molecular mechanism.Methods: Cardiac hypertrophy induced by abdominal aortic constriction (AAC) in mice, dapagliflozin were administered in the drinking water at a dose of 25 mg/kg/d for 12 weeks was observed. Echocardiography was used to detect the changes of cardiac function, including LVEF, LVFS, LVEDd, LVEDs, HR and LV mass. Histological morphological changes were evaluated by Masson trichrome staining and wheat germ agglutinin (WGA) staining. The enrichment of differential genes and signal pathways after treatment was analyzed by gene microarray cardiomyocyte hypertrophy was induced by AngII (2 μM) and the protective effect of dapagliflozin (1 μM) was observed in vitro. The morphological changes of myocardial cells were detected by cTnI immunofluorescence staining. ELISA and qRT-PCR assays were performed to detect the expressions levels of cardiac hypertrophy related molecules.Results: After 12 weeks of treatment, DAPA significantly ameliorated cardiac function and inhibited cardiac hypertrophy in AAC-induced mice. In vitro, DAPA significantly inhibited abnormal hypertrophy in AngII-induced cardiacmyocytes. Both in vivo and in vitro experiments have confirmed that DAPA could mediate the Plin5/PPARα signaling axis to play a protective role in inhibiting cardiac hypertrophy.Conclusion: Dapagliflozin activated the Plin5/PPARα signaling axis and exerts a protective effect against cardiac hypertrophy.

Breeding Severely Vitamin B12-Deficient Mice as Model Animals

2004 ◽  
Vol 74 (1) ◽  
pp. 57-63 ◽  
Author(s):  
Kawata ◽  
Funada ◽  
Wada ◽  
Matsushita ◽  
Sanai ◽  
...  
Keyword(s):  
Body Weight ◽  
Methylmalonic Acid ◽  
Morphological Changes ◽  
Testicular Tissue ◽  
The Body ◽  
Deficient Diet ◽  
Newborn Mice ◽  
Pregnancy And Lactation ◽  
Deficient Mice

Newborn mice weaned from mice fed on a B12-deficient diet during pregnancy and lactation were fed on a B12-deficient diet for 90 days after weaning, and the state of B12 deficiency was evaluated. The effect of B12 deficiency on the testicular tissue was also examined. The body weight of the mice fed on a B12-deficient diet for 90 days was slightly lower than that of the control mice administrated CN-B12, and the urinary excretion of methylmalonic acid (MMA) was increased. The B12 concentrations in the liver and testes were markedly depressed by B12 deficiency, being about 13 and 10 pmol/g, respectively, on day 90. The testes weight was clearly reduced by B12 deficiency. The testes weight/100g body weight was also lowered. Clear morphological changes were observed in the testicular tissue of the B12-deficient mice. These results showed that mice in a severely B12-deficient state could be produced by dietary B12 deprivation. These B12-deficient mice could be useful as model animals not only for elucidating the functions of B12 in vivo, but also for biochemical studies.

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