Rivaroxaban improves vascular response in LPS-induced acute inflammation in experimental models

Rivaroxaban (RVX) was suggested to possess anti-inflammatory and vascular tone modulatory effects. The goal of this study was to investigate whether RVX impacts lipopolysaccharide (LPS)-induced acute vascular inflammatory response. Male rats were treated with 5 mg/kg RVX (oral gavage) followed by 10 mg/kg LPS i.p injection. Circulating levels of IL-6, MCP-1, VCAM-1, and ICAM-1 were measured in plasma 6 and 24 hours after LPS injection, while isolated aorta was used for gene expression analysis, immunohistochemistry, and vascular tone evaluation. RVX pre-treatment significantly reduced LPS mediated increase after 6h and 24h for IL-6 (4.4±2.2 and 2.8±1.7 fold), MCP-1 (1.4±1.5 and 1.3±1.4 fold) VCAM-1 (1.8±2.0 and 1.7±2.1 fold). A similar trend was observed in the aorta for iNOS (5.5±3.3 and 3.3±1.9 folds reduction, P<0.01 and P<0.001, respectively), VCAM-1 (1.3±1.2 and 1.4±1.3 fold reduction, P<0.05), and MCP-1 (3.9±2.2 and 1.9±1.6 fold reduction, P<0.01). Moreover, RVX pre-treatment, improved LPS-induced PE contractile dysfunction in aortic rings (Control vs LPS, Emax reduction = 35.4 and 31.19%, P<0.001; Control vs LPS+RVX, Emax reduction = 10.83 and 11.48%, P>0.05, respectively), resulting in 24.5% and 19.7% change in maximal constriction in LPS and LPS+RVX respectively. These data indicate that RVX pre-treatment attenuates LPS-induced acute vascular inflammation and contractile dysfunction.

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Abstract P21: Free Radicals Mediate Post-shock Contractile Impairment in Cardiomyocytes

Circulation ◽

10.1161/circ.118.suppl_18.s_1449-b ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Min S Tsai ◽

Shijie Sun ◽

Giuseppe Ristagno ◽

Carlos Castillo ◽

Max H Weil ◽

...

Keyword(s):

Free Radicals ◽

Contractile Function ◽

Myocardial Dysfunction ◽

Cellular Level ◽

Male Rats ◽

Contractile Dysfunction ◽

Electrical Shock ◽

Significant Difference ◽

Post Shock ◽

Pre Treatment

Background Previous studies demonstrated myocardial dysfunction after electrical shock and indicated that it may be related to the generation of free radicals. Whether the free radicals are generated after electrical shock has not been documented at the cellular level and its effect on post-shock contractile function has not been clarified. Hypothesis : Electrical shock generates intracellular free radicals inside cardiomyocytes. Reducing intracellular free radicals by pre-treatment of ascorbic acid (AA) would reduce the contractile dysfunction following electrical shock. Methods : Cardiomyocytes isolated from adult male rats were divided into 4 groups, (1) electrical shock alone, (2) electrical shock pre-treated with AA, (3) pre-treated with AA alone and (4) control. AA was administered in an amount of 0.2 mM into the perfusate of the AA + electrical shock and AA groups. Electrical shock of 2 J was delivered in the electrical shock and AA+ electrical shock groups. Results : DCFH-DA loaded cardiomyocytes showed increased intracellular free radicals after electrical shock. The length shortening and Ca 2+ transients were recorded optically with fura-2 loading. Within 4 minutes following electrical shock in the electrical shock group, the length shortening decreased from 8.4±2.5% to 5.6±3.4% ( P =0.000) and the Ca 2+ transient decreased from 1.15±0.13 au to 1.08±0.1 au ( P =0.038). Compared with control, a significant difference in length shortening ( P =0.001) and Ca 2+ transient ( P =0.052) was observed. In the presence of AA, electrical shock did not affect length shortening and Ca 2+ transient. Conclusion: Electrical shock generates intracellular free radicals inside the cardiomyocyte. This is associated with contractile impairment and decrease of Ca 2+ transient. Administering AA may decrease such damage by eliminating free radicals.

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Beneficial effect of retigabine on memory in rats receiving ethanol

Pharmacological Reports ◽

10.1007/s43440-020-00205-z ◽

2020 ◽

Author(s):

Ewa Zwierzyńska ◽

Agata Krupa-Burtnik ◽

Bogusława Pietrzak

Keyword(s):

Beneficial Effect ◽

Fear Conditioning ◽

Morris Water Maze ◽

Water Maze ◽

Experimental Models ◽

Male Rats ◽

Ethanol Administration ◽

Free Access ◽

Oral Gavage ◽

The Impact

Abstract Background Retigabine belongs to the novel generation of antiepileptic drugs but its complex mechanism of action causes that the drug might be effective in other diseases, for instance, alcohol dependence. It is known that ethanol abuse impaired the function of brain structures associated with memory and learning such as the hippocampus. In our previous study, retigabine reduced hippocampal changes induced by ethanol in the EEG rhythms in rabbits. This study is focused on the impact of retigabine on memory processes in male rats receiving alcohol. Methods Memory was evaluated in various experimental models: Morris water maze, Contextual, and Cued Fear Conditioning tests. Retigabine was administered for 3 weeks directly to the stomach via oral gavage at a dose of 10 mg/kg. Rats received also 20% ethanol (5 g/kg/day in two doses) via oral gavage for 3 weeks and had free access to 5% ethanol in the afternoon and at night. Morris water maze was performed after 1 and 3 weeks of ethanol administration and after 1 week from the discontinuation of ethanol administration. Contextual and Cued Fear Conditioning tests were carried out after 24 h and 72 h of alcohol discontinuation. Results The drug significantly decreased ethanol-induced memory disturbances during alcohol administration as well as slightly improved learning processes after the discontinuation of ethanol administration. Conclusions This beneficial effect of retigabine-ethanol interaction on memory may be a relevant element of the drug’s impact on the development of addiction.

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Serotonin stimulates GH secretion through a direct pituitary action: studies in hypophysectomized autografted animals and in perifused pituitaries

Acta Endocrinologica ◽

10.1530/acta.0.1130317 ◽

1986 ◽

Vol 113 (3) ◽

pp. 317-322 ◽

Cited By ~ 12

Author(s):

F. López ◽

D. Gónzalez ◽

E. Aguilar

Keyword(s):

Plasma Volume ◽

Direct Action ◽

Experimental Models ◽

Male Rats ◽

Blood Samples ◽

Kidney Capsule ◽

Gh Secretion ◽

Significant Release ◽

The Right ◽

Dose Dependent

Abstract. To analyze a possible direct action of serotonin (5-hydroxytryptamine) at pituitary level in GH secretion, two experimental models were used: hypophysectomized autografted rats and perifused pituitaries. Adult male rats were hypophysectomized and their own pituitaries placed under the right kidney capsule. Ten days later an intra-atrial cannula was inserted. The next day, blood samples were obtained before and every 10 min during a 2 h period after the injection of saline or 5-hydroxytryptamin (1 or 2 mg/kg iv). Plasma volume was replaced with saline. Both doses of 5-hydroxytryptamine elicit a strong release of GH, the effect being dose-dependent. In pituitaries perifused with 5-hydroxytryptamine (100 μm during 115 min or 1, 10 and 100 μm during 15 min), a significant release of GH was also observed. These results suggested that 5-hydroxytryptamine may stimulate GH secretion through a direct pituitary action.

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Abstract MP45: Deletion Of The Transient Receptor Vanilloid-1 (TRPV1) Channel In Rats Attenuates 2 Kidney 1 Clip Hypertension

Hypertension ◽

10.1161/hyp.78.suppl_1.mp45 ◽

2021 ◽

Vol 78 (Suppl_1) ◽

Author(s):

Sean D Stocker ◽

Leon J DeLalio

Keyword(s):

Heart Rate ◽

Renovascular Hypertension ◽

Sensory Nerve ◽

Experimental Models ◽

Sensory Nerves ◽

Male Rats ◽

Wild Type ◽

Renal Nerve ◽

Trpv1 Channels ◽

Arterial Blood

Renal denervation lowers arterial blood pressure (ABP) in both clinical populations and multiple experimental models of hypertension. This therapeutic effect is partly attributed to the removal of overactive renal sensory nerves that increase sympathetic efferent activity and ABP. Renal sensory nerves highly express TRPV1 channels, and administration of the TRPV1 agonist capsaicin increases renal sensory nerve activity. However, the extent by which TRPV1 channels directly contribute to renal nerve dependent models of hypertension has not been tested. To test this hypothesis, we generated a novel TRPV1 -/- rat using CRISPR/Cas9 and deletion of exon 3. Male and female TRPV1 -/- and wild-type littermates (8-12 weeks) were instrumented with telemetry. At 2 weeks later, renovascular hypertension via renal stenosis was produced by placement of a PTFE cuff (0.16 x 0.22 inches, 1mm long) around the right renal artery. Male TRPV1 -/- and wild-type rats had no differences in baseline mean ABP (99±2 vs 98±3 mmHg, respectively; n=7-9) or heart rate (390±7 vs 400±8 bpm, respectively). Renal stenosis significantly increased mean ABP in both groups; however, mean ABP was significantly lower at Day 28 in male TRPV1 -/- versus wild-type rats (125±8 vs 155±2 mmHg, respectively: P<0.01). Ganglionic blockade with chlorisondamine (2.5mg/kg, sc) at Day 28 produced a smaller fall in mean ABP of male TRPV1 -/- versus wild-type rats (-53±4 vs -86±3 mmHg, respectively; P<0.001). On the other hand, female TRPV1 -/- and wild-type rats had no differences in baseline mean ABP (102±2 vs 104±1 mmHg, respectively; n=6-9) or heart rate (419±8 vs 410±7 bpm, respectively). Renal stenosis significantly increased mean ABP in both groups; however, there were no differences at Day 28 between female TRPV1 -/- versus wild-type rats (117±8 vs 122±6 mmHg, respectively). Moreover, the increase in mean ABP was smaller in females versus males. The ganglionic blocker chlorisondamine produced similar depressor responses in female TRPV1 -/- versus wild-type rats (-64±7 vs -65±7 mmHg, respectively). These findings illustrate a sex difference in renovascular hypertension in rats, but importantly indicate that TRPV1 channels contribute to the established phase of renovascular hypertension in male rats.

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Burning magnesium, a sparkle in acute inflammation: gleams from experimental models

Magnesium Research ◽

10.1684/mrh.2017.0418 ◽

2017 ◽

Vol 30 (1) ◽

pp. 8-15 ◽

Cited By ~ 3

Author(s):

Sara Castiglioni ◽

Alessandra Cazzaniga ◽

Laura Locatelli ◽

Jeanette AM Maier

Keyword(s):

Acute Inflammation ◽

Experimental Models

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Vaccine-Linked Chemotherapy Improves Benznidazole Efficacy for Acute Chagas Disease

Infection and Immunity ◽

10.1128/iai.00876-17 ◽

2018 ◽

Vol 86 (4) ◽

Cited By ~ 13

Author(s):

Kathryn Jones ◽

Leroy Versteeg ◽

Ashish Damania ◽

Brian Keegan ◽

April Kendricks ◽

...

Keyword(s):

Chagas Disease ◽

Experimental Models ◽

Clinical Effects ◽

Water Emulsion ◽

Fold Reduction ◽

Oil In Water ◽

Feasible Option ◽

Chemotherapeutic Treatment ◽

Oil In Water Emulsion ◽

Care Costs

ABSTRACTChagas disease affects 6 to 7 million people worldwide, resulting in significant disease burdens and health care costs in countries of endemicity. Chemotherapeutic treatment is restricted to two parasiticidal drugs, benznidazole and nifurtimox. Both drugs are highly effective during acute disease but are only minimally effective during chronic disease and fraught with significant adverse clinical effects. In experimental models, vaccines can be used to induce parasite-specific balanced TH1/TH2 immune responses that effectively reduce parasite burdens and associated inflammation while minimizing adverse effects. The objective of this study was to determine the feasibility of vaccine-linked chemotherapy for reducing the amount of benznidazole required to significantly reduce blood and tissue parasite burdens. In this study, we were able to achieve a 4-fold reduction in the amount of benznidazole required to significantly reduce blood and tissue parasite burdens by combining the low-dose benznidazole with a recombinant vaccine candidate, Tc24 C4, formulated with a synthetic Toll-like 4 receptor agonist, E6020, in a squalene oil-in-water emulsion. Additionally, vaccination induced a robust parasite-specific balanced TH1/TH2 immune response. We concluded that vaccine-linked chemotherapy is a feasible option for advancement to clinical use for improving the tolerability and efficacy of benznidazole.

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Prevention of Intra-Abdominal Adhesions Using the Combination of Mediclore® and a Statin

European Surgical Research ◽

10.1159/000519708 ◽

2021 ◽

pp. 1-9

Author(s):

Jesung Park ◽

Hyun Kang ◽

Yoo Shin Choi ◽

Suk-Won Suh ◽

Soon Auck Hong ◽

...

Keyword(s):

Chronic Inflammation ◽

Acute Inflammation ◽

Adhesion Formation ◽

Male Rats ◽

Control Group ◽

Fibrosis Score ◽

Abdominal Adhesions ◽

Group Assignment ◽

Control Group Group ◽

Inflammation Score

Purpose: This study investigated the antiadhesive effects of Mediclore®, rosuvastatin, and a combination of Mediclore and rosuvastatin in a rat adhesion model. Methods: The adhesion models (a total of 58 adult male rats) were divided into 4 groups. The control group (group C) received no special materials except for a saline. The experimental groups were treated with 5 mL of Mediclore (group M), rosuvastatin (group R), or rosuvastatin and Mediclore (group RM), and these materials were intraperitoneally placed under the incision. At postoperative day 14, the rats underwent re-laparotomy and adhesiolysis. Three investigators blinded to group assignment scored the extent of adhesion formation, the numbers of remote adhesions, and the extent of acute/chronic inflammation, fibrosis, edema, and congestion on resected specimens via histologic examination. Results: The macroscopic adhesion score in group RM (7.27 ± 3.51) was significantly lower than those in groups C (13.36 ± 2.24) and R (11.71 ± 1.98); group M (9.13 ± 4.09) had a significantly lower adhesion score than group C. The number of remote adhesions was significantly lower in groups R and RM than in group C. The acute inflammation score, chronic inflammation score, and fibrosis score in group RM; the acute inflammation score in group R; and the fibrosis score in group M were significantly lower than those in group C. Conclusion: The intraperitoneal application of Mediclore and a combination of Mediclore and rosuvastatin effectively reduced postoperative adhesions.

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Monoclonal antibodies to type V collagen for immunohistological examination of new tissue deposition associated with biomaterial implants.

Journal of Histochemistry & Cytochemistry ◽

10.1177/39.9.1918939 ◽

1991 ◽

Vol 39 (9) ◽

pp. 1215-1220 ◽

Cited By ~ 18

Author(s):

J A Werkmeister ◽

J A Ramshaw

Keyword(s):

Monoclonal Antibodies ◽

Polyacrylamide Gel Electrophoresis ◽

Experimental Models ◽

Type V Collagen ◽

Tissue Sections ◽

Novel Approach ◽

Wide Range ◽

Conventional Elisa ◽

Pre Treatment ◽

Type V

We developed a panel of highly specific monoclonal antibodies (MAb) against dog Type V collagen. Each antibody showed differential reactivities towards Type V collagen from other species. All the antibodies were highly reactive in conventional ELISA, as well as with electroblots of collagen after polyacrylamide gel electrophoresis using non-denaturing conditions. The MAb were shown to be suitable for the immunohistological detection of Type V collagen in tissue sections, although this normally required pre-treatment of sections with 50 mM acetic acid. In particular, the antibodies were shown to be useful for examining samples of a collagen-based biomaterial, a vascular prosthesis, after explant from evaluation in an animal model. This showed that Type V collagen was most prominent in regions of new tissue formation within the neointima, close to the inner surface of the prosthesis. The broad spectrum of differential reactivities allows the antibodies to be used for a wide range of experimental models. These MAb therefore provide a novel approach for the evaluation of biomaterial performance, particularly for collagen-based implants.

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Effect of vitamin E on cisplatin-induced memory impairment in male rats

Acta Neuropsychiatrica ◽

10.1017/neu.2020.34 ◽

2020 ◽

pp. 1-6

Author(s):

Masoud Hosseinzadeh ◽

Amir Alizadeh ◽

Parnian Heydari ◽

Marzieh Kafami ◽

Mahmoud Hosseini ◽

...

Keyword(s):

Vitamin E ◽

Spatial Memory ◽

Memory Impairment ◽

Saline Solution ◽

Male Rats ◽

Control Group ◽

Sod Activity ◽

The Central Nervous System ◽

Pre Treatment ◽

And Oxidative Stress

Abstract Objective: Neurotoxicity is an adverse effect caused by cisplatin due to inflammation and oxidative stress in the central nervous system. The present study aimed to assess the effects of vitamin E injection on the learning and memory of rats with cisplatin-induced cognitive impairment. Methods: Male rats were administered with cisplatin (2 mg/kg/7 day; intraperitoneally [i i.p.]) and/or vitamin E (200 mg/kg/7 day; i.p.) for 1 week, and the control group received saline solution. Spatial memory was evaluated using Morris water maze (MWM). In addition, the hippocampal concentrations of malondialdehyde (MDA), thiol, and superoxide dismutase (SOD) were measured using biochemical methods. Results: According to the findings, cisplatin significantly increased the escape latency, while decreasing the time spent and travelled pathway in the target quadrant on the final trial day compared to the control group. Furthermore, pre-treatment with vitamin E significantly reversed all the results in the spatial memory test. The biochemical data indicated that vitamin E could decrease MDA activity and increase thiol and SOD activity compared to the control group. Conclusion: According to the results, vitamin E could improve cisplatin-induced memory impairment possibly through affecting the hippocampal oxidative status.

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