scholarly journals Metabolic and cardiac signaling effects of inhaled hydrogen sulfide and low oxygen in male rats

2012 ◽  
Vol 112 (10) ◽  
pp. 1659-1669 ◽  
Author(s):  
Asaf Stein ◽  
Zhengkuan Mao ◽  
Joanna P. Morrison ◽  
Michelle V. Fanucchi ◽  
Edward M. Postlethwait ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Tissue Injury ◽  
Biological Effects ◽  
Male Rats ◽  
Sprague Dawley ◽  
Low Oxygen ◽  
Creatine Kinase Mb ◽  
Gsk 3Β

Low concentrations of inhaled hydrogen sulfide (H2S) induce hypometabolism in mice. Biological effects of H2S in in vitro systems are augmented by lowering O2 tension. Based on this, we hypothesized that reduced O2 tension would increase H2S-mediated hypometabolism in vivo. To test this, male Sprague-Dawley rats were exposed to 80 ppm H2S at 21% O2 or 10.5% O2 for 6 h followed by 1 h recovery at room air. Rats exposed to H2S in 10.5% O2 had significantly decreased body temperature and respiration compared with preexposure levels. Heart rate was decreased by H2S administered under both O2 levels and did not return to preexposure levels after 1 h recovery. Inhaled H2S caused epithelial exfoliation in the lungs and increased plasma creatine kinase-MB activity. The effect of inhaled H2S on prosurvival signaling was also measured in heart and liver. H2S in 21% O2 increased Akt-PSer473 and GSK-3β-PSer9 in the heart whereas phosphorylation was decreased by H2S in 10.5% O2, indicating O2 dependence in regulating cardiac signaling pathways. Inhaled H2S and low O2 had no effect on liver Akt. In summary, we found that lower O2 was needed for H2S-dependent hypometabolism in rats compared with previous findings in mice. This highlights the possibility of species differences in physiological responses to H2S. Inhaled H2S exposure also caused tissue injury to the lung and heart, which raises concerns about the therapeutic safety of inhaled H2S. In conclusion, these findings demonstrate the importance of O2 in influencing physiological and signaling effects of H2S in mammalian systems.

scholarly journals Stamina-Enhancing Effects of Human Adipose-Derived Stem Cells

2021 ◽  
Vol 30 ◽  
pp. 096368972110354
Author(s):  
Eun-Jung Yoon ◽  
Hye Rim Seong ◽  
Jangbeen Kyung ◽  
Dajeong Kim ◽  
Sangryong Park ◽  
...  
Keyword(s):  
Physical Activity ◽  
Stem Cells ◽  
Locomotor Activity ◽  
Tissue Injury ◽  
Male Rats ◽  
Adipose Derived Stem Cells ◽  
Sprague Dawley ◽  
Serum Triglycerides

Stamina-enhancing effects of human adipose derived stem cells (hADSCs) were investigated in young Sprague-Dawley rats. Ten-day-old male rats were transplanted intravenously (IV) or intracerebroventricularly (ICV) with hADSCs (1 × 106 cells/rat), and physical activity was measured by locomotor activity and rota-rod performance at post-natal day (PND) 14, 20, 30, and 40, as well as a forced swimming test at PND 41. hADSCs injection increased the moving time in locomotor activity, the latency in rota-rod performance, and the maximum swimming time. For the improvement of physical activity, ICV transplantation was superior to IV injection. In biochemical analyses, ICV transplantation of hADSCs markedly reduced serum creatine phosphokinase, lactate dehydrogenase, alanine transaminase, and muscular lipid peroxidation, the markers for muscular and hepatic injuries, despite the reduction in muscular glycogen and serum triglycerides as energy sources. Notably, hADSCs secreted brain-derived neurotrophic factor (BDNF) and nerve growth factor in vitro, and increased the level of BDNF in the brain and muscles in vivo. The results indicate that hADSCs enhance physical activity including stamina not only by attenuating tissue injury, but also by strengthening the muscles via production of BDNF.

scholarly journals Studies to Elucidate the Mechanism of Cardio Protective and Hypotensive Activities of Anogeissus acuminata (Roxb. ex DC.) in Rodents

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3471
Author(s):  
Fatima Saqib ◽  
Muhammad Arif Aslam ◽  
Khizra Mujahid ◽  
Luigi Marceanu ◽  
Marius Moga ◽  
...  
Keyword(s):  
Creatine Kinase ◽  
Ex Vivo ◽  
Inflammatory Cells ◽  
Left Ventricular ◽  
Guanosine Monophosphate ◽  
Sprague Dawley ◽  
Positive Effects ◽  
Creatine Kinase Mb

Anogeissus acuminata (Roxb. ex DC.) is a folkloric medicinal plant in Asia; including Pakistan; used as a traditional remedy for cardiovascular disorders. This study was planned to establish a pharmacological basis for the trivial uses of Anogeissus acuminata in certain medical conditions related to cardiovascular systems and to explore the underlying mechanisms. Mechanistic studies suggested that crude extract of Anogeissus acuminata (Aa.Cr) produced in vitro cardio-relaxant and vasorelaxant effects in isolated paired atria and aorta coupled with in vivo decrease in blood pressure by invasive method; using pressure and force transducers connected to Power Lab Data Acquisition System. Moreover; Aa.Cr showed positive effects in left ventricular hypertrophy in Sprague Dawley rats observed hemodynamically by a decrease in cardiac cell size and fibrosis; along with absence of inflammatory cells; coupled with reduced levels of angiotensin converting enzyme (ACE) and renin concentration along with increased concentrations of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP). In Acute Myocardial Infarction (AMI) model; creatine kinase (CK), creatine kinase-MB (CK-MB) and lactic acid dehydrogenase (LDH levels) were found to be decreased; along with decreased necrosis; edema and recruitment of inflammatory cells histologically. In vivo and ex vivo studies of Anogeissus acuminata provided evidence of vasorelaxant; hypotensive and cardioprotective properties facilitated through blockage of voltage-gated Ca++ ion channel; validating its use in cardiovascular diseases

scholarly journals Hypoxia Inducible Factor-1α Overexpression Enhances the Efficacy of Mesenchymal Stem Cells Derived Extracellular Vesicles for Cardiac Repair After Myocardial Infarction

2021 ◽  
Author(s):  
Qingjie Wang ◽  
Le Zhang ◽  
Zhiqin Sun ◽  
Boyu Chi ◽  
Ailin Zou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Mesenchymal Stem Cells ◽  
Cardiac Function ◽  
Extracellular Vesicles ◽  
Biological Effects ◽  
Hypoxia Inducible Factor ◽  
Sprague Dawley

Abstract Aims Naturally secreted extracellular vesicles (EVs) play important roles in stem-mediated cardioprotection. This study aimed to investigate the cardioprotective function and underlying mechanisms of EVs derived from HIF-1a engineered mesenchymal stem cells (MSCs) in a rat model of AMI.Methods and Results EVs isolated from HIF-1a engineered MSCs (HIF-1a-EVs) and control MSCs (MSCs-EVs) were prepared. In in vitro experiments, the EVs were incubated with cardiomyocytes and endothelial cells exposed to hypoxia and serum deprivation (H/SD); in in vivo experiments, the EVs were injected in the acutely infarcted hearts of Sprague-Dawley rats. Compared with MSCs-EVs, HIF-1a-EVs significantly inhibited the apoptosis of cardiomyocytes and enhanced angiogenesis of endothelial cells; meanwhile, HIF-1a-EVs also significantly shrunk fibrotic area and strengthened cardiac function in infarcted rats. After treatment with EVs/RGD-biotin hydrogels, we observed longer retention, higher stability in HIF-1a-EVs, and stronger cardiac function in the rats. Quantitative real-time PCR (qRT-PCR) displayed that miRNA-221-3p was highly expressed in HIF-1a-EVs. After miR-221-3p was inhibited in HIF-1a-EVs, the biological effects of HIF-1a EVs on apoptosis and angiogenesis were attenuated.Conclusion EVs released by MSCs with HIF-1a overexpression can promote the angiogenesis of endothelial cells and the apoptosis of cardiomyocytes via upregulating the expression of miR-221-3p. RGD hydrogels can enhance the therapeutic efficacy of HIF-1a engineered MSC-derived EVs.

scholarly journals Osseointegration of Alkali-Modified NANOZR Implants: An In Vivo Study

2019 ◽  
Vol 20 (4) ◽  
pp. 842 ◽  
Author(s):  
Satoshi Komasa ◽  
Mariko Nishizaki ◽  
Honghao Zhang ◽  
Seiji Takao ◽  
Derong Yin ◽  
...  
Keyword(s):  
Bending Strength ◽  
Bone Marrow Cells ◽  
Alkali Treatment ◽  
Treated Group ◽  
Fluorescent Labeling ◽  
Male Rats ◽  
Sprague Dawley ◽  
Bone Differentiation

Ingredients and surface modification methods are being continually developed to improve osseointegration of dental implants and reduce healing times. In this study, we demonstrate in vitro that, by applying concentrated alkali treatment to NANOZR with strong bending strength and fracture toughness, a significant improvement in the bone differentiation of rat bone marrow cells can be achieved. We investigated the influence of materials modified with this treatment in vivo, on implanted surrounding tissues using polychrome sequential fluorescent labeling and micro-computer tomography scanning. NANOZR implant screws in the alkali-treated group and the untreated group were evaluated after implantation in the femur of Sprague–Dawley male rats, indicating that the amount of new bone in the alkali-modified NANOZR was higher than that of unmodified NANOZR. Alkali-modified NANOZR implants proved to be useful for the creation of new implant materials.

scholarly journals Involvement of S100A8/A9-TLR4-NLRP3 Inflammasome Pathway in Contrast-Induced Acute Kidney Injury

2017 ◽  
Vol 43 (1) ◽  
pp. 209-222 ◽  
Author(s):  
Xuexian Tan ◽  
Xiaohe Zheng ◽  
Zena Huang ◽  
Jiaqiong Lin ◽  
Chuli Xie ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Nlrp3 Inflammasome ◽  
Tissue Injury ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Underlying Mechanism ◽  
Male Rats ◽  
Ros Generation

Background: Contrast-induced acute kidney injury (CIAKI) is a common cause of hospital-acquired acute kidney injury (AKI). S100A8/A9-TLR4-NLRP3 inflammasome pathway triggers inflammation, apoptosis and tissue injury in several AKI models. Nevertheless, the underlying mechanism of S100A8/A9-TLR4-NLRP3 inflammasome pathway in CIKAI is not clear. We aimed to investigate the possible role of S100A8/A9-TLR4-NLRP3 inflammasome in the pathophysiology of CIAKI. Methods: We treated male rats and NRK-52E cells by iopromide to establish in vivo and in vitro models of CIAKI. We collected serum and urine samples to detect renal function. We obtained kidney tissue for histological analysis and detection of protein concentration. We used inhibitor of TLR4 and NLRP3-siRNA to further testify their role in CIAKI in NRK-52E cells. Results: Iopromide caused elevation of SCr, BUN and NGAL level, decrease of endogenous creatinine clearance, morphological injury and tubular apoptosis, enhanced IL-1β and IL-18 expression, and increased expression of S100A8/A9, TLR4 and NLRP3 inflammsome. In NRK-52E cells, iopromide caused enhanced apoptotic rates and ROS generation, which could be ameliorated by inhibitor of TLR4 and NLRP3-siRNA. Moreover, inhibition of TLR4 dampened NLRP3 expression. Conclusion: S100A8/A9-TLR4-NLRP3 inflammasome pathway represented a key mechanism of CI-AKI, which provided a potential therapeutic target.

scholarly journals Ghrelin Ameliorates Angiotensin II-Induced Myocardial Fibrosis by Upregulating Peroxisome Proliferator-Activated Receptor Gamma in Young Male Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Qian Wang ◽  
Xin Sui ◽  
Rui Chen ◽  
Pei-Yong Ma ◽  
Yong-Liang Teng ◽  
...  
Keyword(s):  
Myocardial Fibrosis ◽  
Transforming Growth Factor ◽  
Cardiac Fibroblasts ◽  
Male Rats ◽  
Peroxisome Proliferator ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Collagen Iii

Angiotensin (Ang) II contributes to the formation and development of myocardial fibrosis. Ghrelin, a gut peptide, has demonstrated beneficial effects against cardiovascular disease. In the present study, we explored the effect and related mechanism of Ghrelin on myocardial fibrosis in Ang II-infused rats. Adult Sprague-Dawley (SD) rats were divided into 6 groups: Control, Ang II (200ng/kg/min, microinfusion), Ang II+Ghrelin (100μg/kg, subcutaneously twice daily), Ang II+Ghrelin+GW9662 (a specific PPAR-γinhibitor, 1 mg/kg/d, orally), Ang II+GW9662, and Ghrelin for 4 wks. In vitro, adult rat cardiac fibroblasts (CFs) were pretreated with or without Ghrelin, Ghrelin+GW9662, or anti-Transforming growth factor (TGF)-β1 antibody and then stimulated with or without Ang II (100 nmol/L) for 24 h. Ang II infusion significantly increased myocardial fibrosis, expression of collagen I, collagen III, and TGF-β1, as well as TGF-β1 downstream proteins p-Smad2, p-Smad3, TRAF6, and p-TAK1 (all p<0.05). Ghrelin attenuated these effects. Similar results were seen in Ang II-stimulated rat cardiac fibroblasts in vitro. In addition, Ghrelin upregulated PPAR-γexpressionin vivoandin vitro, and treatment with GW9662 counteracted the effects of Ghrelin. In conclusion, Ghrelin ameliorated Ang II-induced myocardial fibrosis by upregulating PPAR-γand in turn inhibiting TGF-β1signaling.

In vivo and in vitro percutaneous absorption of [14C]pyrene in Sprague Dawley male rats: skin reservoir effect and consequence on urinary 1-OH pyrene excretion

2008 ◽  
Vol 82 (10) ◽  
pp. 739-747 ◽  
Author(s):  
Jean-Paul Payan ◽  
Michel Lafontaine ◽  
Patrice Simon ◽  
Fabrice Marquet ◽  
Catherine Champmartin-Gendre ◽  
...  
Keyword(s):  
Percutaneous Absorption ◽  
Male Rats ◽  
Sprague Dawley ◽  
Reservoir Effect ◽  
Skin Reservoir ◽  
In Vitro Percutaneous Absorption

scholarly journals Network Pharmacology–Based Analysis and Experimental Exploration of Antidiabetic Mechanisms of Gegen Qinlian Decoction

2021 ◽  
Vol 12 ◽  
Author(s):  
Yu Xu ◽  
Jihan Huang ◽  
Ning Wang ◽  
Hor-Yue Tan ◽  
Cheng Zhang ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Stress Reduction ◽  
Metabolic Diseases ◽  
Tissue Injury ◽  
Biological Effects ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Antidiabetic Effects

Type-2 diabetes mellitus (T2DM) and therapy options have been studied increasingly due to their rising incidence and prevalence. The trend of applying traditional Chinese medicine (TCM) to treat T2DM is increasing as a crucial medical care for metabolic dysfunctions. Gegen Qinlian decoction (GQL), a well-known classical TCM formula used in China, has been clinically applied to treat various types of chronic metabolic diseases. However, antidiabetic effects of GQL administration during T2DM have never been studied systematically. We assessed physiological and molecular targets associated with therapeutic effects of GQL by evaluating network topological characteristics. The GQL-related biological pathways are closely associated with antidiabetic effects, including the TNF and PI3K–AKT signaling pathways. Associated primary biological processes such as RNA polymerase II promoter transcription participate in the inflammatory response, oxidative stress reduction, and glucose metabolic process, thereby exerting multiple biological effects on the antidiabetic mechanism. Furthermore, our results showed that GQL can affect blood glycemic levels and ameliorate inflammatory symptoms, and liver and pancreas tissue injury in high-fat diet plus streptozotocin-induced diabetic mice. In vivo and in vitro experiments confirmed that antidiabetic effects of GQL were associated with a modulation of the TNF and PI3K–AKT–MTOR pathways.

BINDING AND METABOLISM OF 5α-ANDROSTANE-3α,17β-DIOL AND OF 5α-ANDROSTANE-3β,17β-DIOL IN THE PROSTATE, SEMINAL VESICLES AND PLASMA OF MALE RATS: STUDIES IN VIVO AND IN VITRO

1975 ◽  
Vol 64 (3) ◽  
pp. 529-538 ◽  
Author(s):  
M. KRIEG ◽  
H.-J. HORST ◽  
M.-L. STERBA
Keyword(s):  
Skeletal Muscle ◽  
Specific Binding ◽  
Biological Effects ◽  
Sucrose Density Gradient ◽  
Total Radioactivity ◽  
Seminal Vesicles ◽  
Male Rats ◽  
Cytosol Fraction

SUMMARY Binding of 5α-androstane-3α,17β-diol (3α-diol) and 5α-androstane-3β,17β-diol (3β-diol) in vivo and in vitro to the 100000 g cytosol fraction of the rat prostate and seminal vesicles as well as to plasma was studied by agargel electrophoresis and sucrose density gradient ultracentrifugation and the results compared with the corresponding findings for 5α-dihydrotestosterone (5α-DHT). The metabolism of 3α-diol and 3β-diol was also investigated by thin-layer chromatography. The following results were obtained: (1) A specific binding of 3α-diol and 3β-diol by the cytosols could not be demonstrated in vitro, while 5α-DHT was specifically bound. (2) In plasma, 3α-diol was extensively bound, 3β-diol less extensively bound, while 5α-DHT remained unbound. (3) After intravenous injection of 3α-diol, specifically bound radioactivity, increasing within 30 min, was found in the prostate cytosol, while after 3β-diol injection no binding occurred. (4) Parallel to the increased binding, the total radioactivity in the prostate accumulated within 30 min after 3α-diol injection, the uptake being 5·3 times higher than in skeletal muscle. However after 3β-diol injection, total radioactivity decreased in the prostate within 30 min, the uptake being only 1·5 times higher than in skeletal muscle. (5) One minute after injection of 3α-diol, 53% of the extracted radioactivity in the prostate had been converted to 5α-DHT, this increased within 30 min to 81%. Thirty minutes after the injection of 3β-diol, about 32% of the extracted radioactivity in the prostate had been converted to 5α-DHT. (6) From the in-vivo and in-vitro experiments it was concluded that 3α-diol exerts its biological effects mainly by its conversion into 5α-DHT.

Nonylphenol induced apoptosis and autophagy involving the Akt/mTOR pathway in prepubertal Sprague-Dawley male rats in vivo and in vitro

Toxicology ◽  
2016 ◽  
Vol 373 ◽  
pp. 41-53 ◽  
Author(s):  
Wenting Huang ◽  
Chao Quan ◽  
Peng Duan ◽  
Sha Tang ◽  
Wei Chen ◽  
...  
Keyword(s):  
Mtor Pathway ◽  
Male Rats ◽  
Sprague Dawley ◽  
Induced Apoptosis
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