Abstract P141: Cardiac TRH Partly Mediates Angiotensin II-induced Fibrotic and Hypertrophy Effects in "in vivo" and "in vitro" Models

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Silvia I García ◽  
Ludmila S Peres Diaz ◽  
Maia Aisicovich ◽  
Mariano L Schuman ◽  
María S Landa
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Cardiac Hypertrophy ◽  
Structural Changes ◽  
In Vitro Models ◽  
Heart Weight ◽  
Saline Control ◽  
Control Group

Cardiac TRH (cTRH) is overexpressed in the hypertrophied ventricle (LV) of the SHR. Additionally in vivo siRNA-TRH treatment induced downregulation of LV-TRH preventing cardiac hypertrophy and fibrosis demonstrating that TRH is involved in hypertrophic and fibrotic processes. Moreover, in a normal heart, the increase of LV TRH expression alone could induce structural changes where fibrosis and hypertrophy could be involved, independently of any other system alterations. Is well-known the cardiac hypertrophy/ fibrotic effects induced by AII, raising the question of whether specific LV cTRH inhibition might attenuates AII induced cardiac hypertrophy and fibrosis in mice. We challenged C57 mice with AII (osmotic pumps,14 days; 2 mg/kg) to induce cardiac hypertrophy vs saline. Groups were divided and , simultaneously to pump surgery, injected intracardiac with siRNA-TRH and siRNA-Con as its control. Body weight, water consume and SABP were measured daily. As expected, AII significantly increased SABP (p<0.05) in both groups treated , although cardiac hypertrophy (heart weight/body weight) was only evident in the group with the cardiac TRH system undamaged, suggesting that the cardiac TRH system function as a necessary mediator of the AII-induced hypertrophic effect. As hypothesized, we found an AII-induced increase of TRH (p<0.05) gene expression (real-t PCR) confirmed by immunofluorescence that was not observed in the group AII+siRNA-TRH demonstrating the specific siRNA treatment efficiency. Furthermore, AII significantly increase (p<0.05) BNP (hypertrophic marker), III collagen and TGFB (fibrosis markers) expressions only in the group with AII with the cardiac TRH system intact. On the contrary, the group with AII and the cTRH system inhibited, shows genes expressions similar to the saline control group. We confirmed these results by immunofluorescence. Similar fibrotic results were observed with NIH3T3 cell culture where we demonstrated that AII induced TRH gene expression (p<0.05) and its inhibition impedes AII-induced increase of TGFB and III/I collagens expressions telling us about the role of the cTRH in the AII fibrosis effects. Our results point out that the cardiac TRH is involved in the AII-induced hypertrophic and fibrotic effects.

scholarly journals Anti-Obesity and Anti-Adipogenic Effects of Chitosan Oligosaccharide (GO2KA1) in SD Rats and in 3T3-L1 Preadipocytes Models

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 331
Author(s):  
Jung-Yun Lee ◽  
Tae Yang Kim ◽  
Hanna Kang ◽  
Jungbae Oh ◽  
Joo Woong Park ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Density Lipoprotein ◽  
Treated Group ◽  
Control Group ◽  
Chitosan Oligosaccharide ◽  
Sd Rats ◽  
Adipogenic Gene

Excess body weight is a major risk factor for type 2 diabetes (T2D) and associated metabolic complications, and weight loss has been shown to improve glycemic control and decrease morbidity and mortality in T2D patients. Weight-loss strategies using dietary interventions produce a significant decrease in diabetes-related metabolic disturbance. We have previously reported that the supplementation of low molecular chitosan oligosaccharide (GO2KA1) significantly inhibited blood glucose levels in both animals and humans. However, the effect of GO2KA1 on obesity still remains unclear. The aim of the study was to evaluate the anti-obesity effect of GO2KA1 on lipid accumulation and adipogenic gene expression using 3T3-L1 adipocytes in vitro and plasma lipid profiles using a Sprague-Dawley (SD) rat model. Murine 3T3-L1 preadipocytes were stimulated to differentiate under the adipogenic stimulation in the presence and absence of varying concentrations of GO2KA1. Adipocyte differentiation was confirmed by Oil Red O staining of lipids and the expression of adipogenic gene expression. Compared to control group, the cells treated with GO2KA1 significantly decreased in intracellular lipid accumulation with concomitant decreases in the expression of key transcription factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (CEBP/α). Consistently, the mRNA expression of downstream adipogenic target genes such as fatty acid binding protein 4 (FABP4), fatty acid synthase (FAS), were significantly lower in the GO2KA1-treated group than in the control group. In vivo, male SD rats were fed a high fat diet (HFD) for 6 weeks to induced obesity, followed by oral administration of GO2KA1 at 0.1 g/kg/body weight or vehicle control in HFD. We assessed body weight, food intake, plasma lipids, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) for liver function, and serum level of adiponectin, a marker for obesity-mediated metabolic syndrome. Compared to control group GO2KA1 significantly suppressed body weight gain (185.8 ± 8.8 g vs. 211.6 ± 20.1 g, p < 0.05) with no significant difference in food intake. The serum total cholesterol, triglyceride, and low-density lipoprotein (LDL) levels were significantly lower in the GO2KA1-treated group than in the control group, whereas the high-density lipoprotein (HDL) level was higher in the GO2KA1 group. The GO2KA1-treated group also showed a significant reduction in ALT and AST levels compared to the control. Moreover, serum adiponectin levels were significantly 1.5-folder higher than the control group. These in vivo and in vitro findings suggest that dietary supplementation of GO2KA1 may prevent diet-induced weight gain and the anti-obesity effect is mediated in part by inhibiting adipogenesis and increasing adiponectin level.

Abstract 20118: Defining the Sufficiency of Atg7 to Suppress Phenylephrine-induced Cardiac Hypertrophy

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Marcus Tjeerdsma ◽  
Levi Froke ◽  
Jessica Freeling ◽  
Scott Pattison
Keyword(s):  
Body Weight ◽  
Cardiac Hypertrophy ◽  
Cardiac Function ◽  
Heart Weight ◽  
Autophagic Flux ◽  
Specific Expression ◽  
Hypertrophic Growth ◽  
Fractional Shortening

Introduction: Macroautophagy is a process of bulk protein degradation. Our prior work showed that Atg7 expression is sufficient to induce autophagic flux in vitro and in vivo . When Atg7 was co-expressed with CryAB R120G in the heart, cardiac hypertrophy was blunted in heart weight/body weight ratios and fetal gene expression markers. To determine if Atg7 expression is sufficient to limit hypertrophic growth in another model, we tested the effects of Atg7 overexpression with phenylephrine-induced hypertrophy both in vitro and in vivo . Hypothesis: Atg7 will blunt the hypertrophic effects of phenylephrine. Methods: Rat neonatal cardiomyocytes were infected with adenoviruses expressing either LacZ or Atg7 and treated with phenylephrine to induce cardiomyocytes hypertrophy. Osmotic pumps were surgically implanted into control mice and mice with cardiac-specific expression of Atg7 to infuse phenylephrine (PE) or vehicle (saline) for four weeks. Results: PE treatment significantly increased neonatal cardiomyocyte areas in LacZ-expressing cells, while Atg7-expressing cardiomyocytes showed no growth. In mice, all genotypes responded to PE treatment with significantly increased heart weight/body weight ratios and increased fiber size. However, Atg7-expressing hearts differed significantly from control hearts in normalized heart mass following PE delivery. Vehicle treated Atg7-expressing hearts had 17% smaller myofiber cross-sectional areas than those from control genotypes and had a reduced hypertrophic response to PE, relative to controls. Echocardiography showed that Atg7-expressing hearts had significantly elevated cardiac function (% fractional shortening) prior to and throughout the experiment over control hearts (33% vs. 29%). PE significantly increased fractional shortening) from 29% to 36% in control hearts, but failed to significantly elevate cardiac function in Atg7-expressing hearts further (33% vs 35%). Additional assays are underway to understand the Atg7-dependent adaptations to PE. Conclusion: Atg7 expression yields modestly smaller hearts with enhanced cardiac function which may protect them from hypertrophic stresses like phenylephrine.

scholarly journals Interaction of Lactoferrin with Unsaturated Fatty Acids: In Vitro and In Vivo Study of Human Lactoferrin/Oleic Acid Complex Cytotoxicity

Materials ◽  
2021 ◽  
Vol 14 (7) ◽  
pp. 1602
Author(s):  
Anna Elizarova ◽  
Alexey Sokolov ◽  
Valeria Kostevich ◽  
Ekaterina Kisseleva ◽  
Evgeny Zelenskiy ◽  
...  
Keyword(s):  
Oleic Acid ◽  
Structural Changes ◽  
Unsaturated Fatty Acids ◽  
Structural Features ◽  
Control Group ◽  
Acid Complex ◽  
Hepatoma 22A ◽  
Constitutive Parameters

As shown recently, oleic acid (OA) in complex with lactoferrin (LF) causes the death of cancer cells, but no mechanism(s) of that toxicity have been disclosed. In this study, constitutive parameters of the antitumor effect of LF/OA complex were explored. Complex LF/OA was prepared by titrating recombinant human LF with OA. Spectral analysis was used to assess possible structural changes of LF within its complex with OA. Structural features of apo-LF did not change within the complex LF:OA = 1:8, which was toxic for hepatoma 22a cells. Cytotoxicity of the complex LF:OA = 1:8 was tested in cultured hepatoma 22a cells and in fresh erythrocytes. Its anticancer activity was tested in mice carrying hepatoma 22a. In mice injected daily with LF-8OA, the same tumor grew significantly slower. In 20% of animals, the tumors completely resolved. LF alone was less efficient, i.e., the tumor growth index was 0.14 for LF-8OA and 0.63 for LF as compared with 1.0 in the control animals. The results of testing from 48 days after the tumor inoculation showed that the survival rate among LF-8OA-treated animals was 70%, contrary to 0% rate in the control group and among the LF-treated mice. Our data allow us to regard the complex of LF and OA as a promising tool for cancer treatment.

scholarly journals Effects of Vitrification on the Blastocyst Gene Expression Profile in a Porcine Model

2021 ◽  
Vol 22 (3) ◽  
pp. 1222
Author(s):  
Cristina Cuello ◽  
Cristina A. Martinez ◽  
Josep M. Cambra ◽  
Inmaculada Parrilla ◽  
Heriberto Rodriguez-Martinez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Analysis ◽  
Survival Rates ◽  
Control Group ◽  
P Value ◽  
Transcriptome Profile ◽  
Embryo Viability ◽  
The Impact

This study was designed to investigate the impact of vitrification on the transcriptome profile of blastocysts using a porcine (Sus scrofa) model and a microarray approach. Blastocysts were collected from weaned sows (n = 13). A total of 60 blastocysts were vitrified (treatment group). After warming, vitrified embryos were cultured in vitro for 24 h. Non-vitrified blastocysts (n = 40) were used as controls. After the in vitro culture period, the embryo viability was morphologically assessed. A total of 30 viable embryos per group (three pools of 10 from 4 different donors each) were subjected to gene expression analysis. A fold change cut-off of ±1.5 and a restrictive threshold at p-value < 0.05 were used to distinguish differentially expressed genes (DEGs). The survival rates of vitrified/warmed blastocysts were similar to those of the control (nearly 100%, n.s.). A total of 205 (112 upregulated and 93 downregulated) were identified in the vitrified blastocysts compared to the control group. The vitrification/warming impact was moderate, and it was mainly related to the pathways of cell cycle, cellular senescence, gap junction, and signaling for TFGβ, p53, Fox, and MAPK. In conclusion, vitrification modified the transcriptome of in vivo-derived porcine blastocysts, resulting in minor gene expression changes.

Prostaglandin F2 alpha induces cardiac myocyte hypertrophy in vitro and cardiac growth in vivo

1996 ◽  
Vol 271 (6) ◽  
pp. H2197-H2208 ◽  
Author(s):  
J. Lai ◽  
H. Jin ◽  
R. Yang ◽  
J. Winer ◽  
W. Li ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Cardiac Myocyte ◽  
Ventricular Myocytes ◽  
Chronic Administration ◽  
Heart Weight ◽  
Adult Rats ◽  
Myocyte Hypertrophy ◽  
Cardiac Myocyte Hypertrophy

Several prostaglandins [prostaglandin (PG) A2, -B2, -D2, -E2, -F2 alpha, and -I2 and carbaprostacyclin] and the thromboxane analogue U-46619 were analyzed for the ability to induce hypertrophy of rat neonatal cardiac ventricular myocytes. Myocyte hypertrophy was induced specifically by PGF2 alpha. Myocytes exposed to this prostanoid in culture increased in size and protein content. The contractile fibrils within the cells became organized into parallel arrays, and the cells tended to cluster and beat spontaneously. PGF2 alpha also induced the expression of c-fos, atrial natriuretic factor (ANF), and alpha-skeletal actin in these cells. The effects of PGF2 alpha were compared with several known cardiac myocyte hypertrophy factors (phenylephrine, endothelin-1, leukemia inhibitory factor, cardiotrophin-1, and angiotensin II). PGF2 alpha was found to be intermediate in potency among the factors but induced a level of ANF production that was approximately 10-fold higher than any of the other effectors. Responsiveness to PGF2 alpha was not limited to neonatal cardiocytes. Ventricular myocytes isolated from adult rats also responded specifically to PGF2 alpha with a morphological change similar to that observed with phenylephrine and by producing ANF. In rats, chronic administration of fluprostenol, a potent agonist analogue of PGF2 alpha, resulted in a dose-dependent increase in heart weight- and ventricular weight-to-body weight ratios. The amount of PGF2 alpha extractable from the hearts of rats with cardiac hypertrophy induced by myocardial infarction was also found to be greater than that in sham-operated control rats. These results indicate that PGF2 alpha may play an important role in inducing cardiac hypertrophy.

scholarly journals Allylmethylsulfide, a Sulfur Compound Derived from Garlic, Attenuates Isoproterenol-Induced Cardiac Hypertrophy in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Soheb Anwar Mohammed ◽  
Bugga Paramesha ◽  
Yashwant Kumar ◽  
Ubaid Tariq ◽  
Sudheer Kumar Arava ◽  
...  
Keyword(s):  
Body Weight ◽  
Cardiac Hypertrophy ◽  
Weight Ratio ◽  
Chronic Administration ◽  
The Body ◽  
Heart Weight ◽  
Serum Biochemical ◽  
Enalapril Treatment ◽  
Histopathological Investigation

Allylmethylsulfide (AMS) is a novel sulfur metabolite found in the garlic-fed serum of humans and animals. In the present study, we have observed that AMS is safe on chronic administration and has a potential antihypertrophic effect. Chronic administration of AMS for 30 days did not cause any significant differences in the body weight, electrocardiogram, food intake, serum biochemical parameters, and histopathology of vital organs. Single-dose pharmacokinetics of AMS suggests that AMS is rapidly metabolized into Allylmethylsulfoxide (AMSO) and Allylmethylsulfone (AMSO2). To evaluate the efficacy of AMS, cardiac hypertrophy was induced by subcutaneous implantation of ALZET® osmotic minipump containing isoproterenol (~5 mg/kg/day), cotreated with AMS (25 and 50 mg/kg/day) and enalapril (10 mg/kg/day) for 2 weeks. AMS and enalapril significantly reduced cardiac hypertrophy as studied by the heart weight to body weight ratio and mRNA expression of fetal genes (ANP and β-MHC). We have observed that TBARS, a parameter of lipid peroxidation, was reduced and the antioxidant enzymes (glutathione, catalase, and superoxide dismutase) were improved in the AMS and enalapril-cotreated hypertrophic hearts. The extracellular matrix (ECM) components such as matrix metalloproteinases (MMP2 and MMP9) were significantly upregulated in the diseased hearts; however, with the AMS and enalapril, it was preserved. Similarly, caspases 3, 7, and 9 were upregulated in hypertrophic hearts, and with the AMS and enalapril treatment, they were reduced. Further to corroborate this finding with in vitro data, we have checked the nuclear expression of caspase 3/7 in the H9c2 cells treated with isoproterenol and observed that AMS cotreatment reduced it significantly. Histopathological investigation of myocardium suggests AMS and enalapril treatment reduced fibrosis in hypertrophied hearts. Based on our experimental results, we conclude that AMS, an active metabolite of garlic, could reduce isoproterenol-induced cardiac hypertrophy by reducing oxidative stress, apoptosis, and stabilizing ECM components.

scholarly journals Antinociceptive and Antioxidant Activities of Phytol In Vivo and In Vitro Models

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Camila Carolina de Menezes Patrício Santos ◽  
Mirian Stiebbe Salvadori ◽  
Vanine Gomes Mota ◽  
Luciana Muratori Costa ◽  
Antonia Amanda Cardoso de Almeida ◽  
...  
Keyword(s):  
Antioxidant Activities ◽  
Antioxidant Properties ◽  
Thiobarbituric Acid ◽  
In Vitro Models ◽  
Control Group ◽  
Second Phase ◽  
Hot Plate Test ◽  
Antinociceptive Effects

The objective of the present study was to evaluate the antinociceptive effects of phytol using chemical and thermal models of nociception in mice and to assess its antioxidant effects in vitro. Phytol was administered intraperitoneally (i.p.) to mice at doses of 25, 50, 100, and 200 mg/kg. In the acetic acid-induced writhing test, phytol significantly reduced the number of contortions compared to the control group (P<0.001). In the formalin test, phytol reduced significantly the amount of time spent in paw licking in both phases (the neurogenic and inflammatory phases), this effect being more pronounced in the second phase (P<0.001). Phytol also provoked a significant increase in latency in the hot plate test. These antinociceptive effects did not impaire the motor performance, as shown in the rotarod test. Phytol demonstrated a strong antioxidant effect in vitro in its capacity to remove hydroxyl radicals and nitric oxide as well as to prevent the formation of thiobarbituric acid reactive substances (TBARS). Taken as a whole, these results show the pronounced antinociceptive effects of phytol in the nociception models used, both through its central and peripheral actions, but also its antioxidant properties demonstrated in the in vitro methods used.

scholarly journals VIABILITAS BAKTERI PROBIOTIK IN-VITRO DAN PENGARUH PEMBERIAN AIR OKSIGEN TERHADAP PERTUMBUHAN BAKTERI PROBIOTIK SECARA IN-VIVO

2007 ◽  
Vol 2 (1) ◽  
pp. 22
Author(s):  
Enok Sobariah ◽  
Ali Khomsan ◽  
Ingrid S. Surono
Keyword(s):  
Body Weight ◽  
Lactic Acid ◽  
Lactic Acid Bacteria ◽  
Day Treatment ◽  
The Body ◽  
Probiotic Bacteria ◽  
Control Group ◽  
Oxygenated Water

<p class="MsoNormal" style="margin: 0cm 12.45pt 6pt 17.85pt; text-align: justify;"><span style="font-size: 10pt;" lang="en-us" xml:lang="en-us">The aim of this study were  to identify the in-vitro tolerance of pro-biotic bacteria to acid and bile salt condition; and  to prove a hypothesis that the supplementation of oxygenated water has a positive effect on the body weight of rat and on viability of pro-biotic bacteria.  The first study was carried out at PAU Laboratory of Bogor Agricultural University, while the second study was conducted at Department of Community Nutrition of Bogor Agricultural University and Microbiology Laboratory of Indonesia Institute of Technology. Forty five rats aged 6 weeks were divided into three groups, i.e., control group without probiotic (a0), Lactobacillus casei Shirota (a1), and Lactobacillus IS-7257 (a2).  Each group (consisting of 5 rats each) has three different treatments, namely, control without oxygenated water (b0), 50 ppm oxygenated water (b2), and 80 ppm oxygenated water (b2). Oxygenated water was administered to the rats twice a day in the morning (3.25 ml) and afternoon (3.00 ml). Observation was carried out on the body  weight of the rats, fecal lactic acid bacteria, coliform, and anaerob bacteria by plate counting, for 4 periods, i.e, prior to the treatment (C0), after three-day treatment (C1), after seven-day treatment (C2), and on the 10<sup>th</sup> day treatment or three days after washed out period. The results indicated that probiotic bacteria are resistant to acid and bile acid condition. Oxygen concentration in water has a significant positive influence on the body weight of rats towards viability of probiotic bacteria (p-level &lt; 0.05).  The supplementation of  oxygenated water 50 ppm significantly increase the population of viable fecal lactic acid bacteria in L. casei Shirota and Lactobacillus IS-7257 groups after 3 and 7 days of treatment.  Lactobacillus IS-7257 gave better response than L. casei Shirota. The supplementation of oxygenated water 80 ppm significantly reduces the fecal coliform in-vivo in both L. casei Shirota and Lactobacillus IS-7257 groups (p-level &lt; 0.05).</span></p>

scholarly journals In vitro and in vivo anti-trypanosomal potentials of Afrormosia laxiflora and Khaya senegalensis against Trypanosoma brucei brucei

2018 ◽  
Vol 39 (3) ◽  
pp. 269-284
Author(s):  
G.D. Chechet ◽  
J Yahaya ◽  
A.J. Nok
Keyword(s):  
Body Weight ◽  
Trypanosoma Brucei ◽  
Post Infection ◽  
Methanol Extract ◽  
Control Group ◽  
Phytochemical Analysis ◽  
Trypanosoma Brucei Brucei ◽  
Khaya Senegalensis

Animal African trypanosomiasis (AAT) also known as Nagana is a resurgent disease in Africa. Medicinal plants are being used in less developed countries for the treatment of various diseases including trypanosomiasis, due to the high cost of currently available drugs. Most of these plants have been useful sources of treatment of various diseases based on information obtained from folk medicine but have not been scientifically certified. Here, we investigated the in vitro and in vivo anti-trypanosomal potentials of the methanol extract of Aformorsia laxiflora and Khaya senegalensis against T. b. brucei. Phytochemical screening as well as LD50 of the plant extracts was carried out following standard procedures. Parasitemia was monitored daily while Packed Cell Volume was determined at three time points (days 1, 4 and 7) during the course of the infection. The phytochemical analysis showed the presence of saponins, alkaloids, flavonoids, antraquinones, resins and tanins. However, steriods/terpenoids were absent in K. senegalensis but present in A. laxiflora. The toxicity of methanol extract of both A. laxiflora and K. senegalensis was above 5000mg/kg body weight. Methanol extracts of A. laxiflora (leaves) and K. senegalensis (stem bark) showed promising trypanocidal potential in vitro against T. b. brucei at concentrations of 10, 15, 25mg/ml and 40 and 20mg/ml respectively. At these concentrations, both extracts immobilized the parasites within 55mins post-incubation. In general, A. laxiflora leaf extract demonstrated prophylactic activity against T. b. brucei in vivo at a dose of 500mg/Kg body weight particularly in group C animals where a delayed pre-patent period (6 days post-infection), extended survival (14 days post-infection) and significant (P<0.05) reduction in the parasite burden confirmed by an absence of anemia (PCV 47.00±0.8 %) was observed when compared to the infected untreated control group. K. senegalensis extract on the other hand did not show anti-trypanosomal activity in the treated groups (1, 2, and 3). Based on these observations, it was therefore deduced that the methanol extract of leaves of A. laxiflora possessed the ability to ameliorate the burden of the disease and could be a plausible candidate for drug development against the disease.Keywords: Trypanosoma brucei brucei, Afromosia laxiflora, Khaya senegalensis, anti-trypanosomal, in vitro, in vivo

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