Su2080 Limited Nesting Stress Alters Maternal Behavior and In Vivo Intestinal Permeability in a Sex-Dependent Manner in Wistar Rat Pups

Sulfasalazine is characterized by low intestinal absorption, which essentially enables its colonic targeting and therapeutic action. The mechanisms behind this low absorption have not yet been elucidated. The purpose of this study was to investigate the role of efflux transporters in the intestinal absorption of sulfasalazine as a potential mechanism for its low small-intestinal absorption and colonic targeting following oral administration. The effects of P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2), and breast cancer resistance protein (BCRP) inhibitors on sulfasalazine bidirectional permeability were studied across Caco-2 cell monolayers, including dose-response analysis. Sulfasalazine in vivo permeability was then investigated in the rat jejunum by single-pass perfusion, in the presence vs. absence of inhibitors. Sulfasalazine exhibited 19-fold higher basolateral-to-apical (BL-AP) than apical-to-basolateral (AP-BL) Caco-2 permeability, indicative of net mucosal secretion. MRP2 inhibitors (MK-571 and indomethacin) and BCRP inhibitors [fumitremorgin C (FTC) and pantoprazole] significantly increased AP-BL and decreased BL-AP sulfasalazine Caco-2 transport in a concentration-dependent manner. No effect was observed with the P-gp inhibitors verapamil and quinidine. The IC50 values of the specific MRP2 and BCRP inhibitors MK-571 and FTC on sulfasalazine secretion were 21.5 and 2.0 μM, respectively. Simultaneous inhibition of MRP2 and BCRP completely abolished sulfasalazine Caco-2 efflux. Without inhibitors, sulfasalazine displayed low (vs. metoprolol) in vivo intestinal permeability in the rat model. MK-571 or FTC significantly increased sulfasalazine permeability, bringing it to the low-high permeability boundary. With both MK-571 and FTC present, sulfasalazine displayed high permeability. In conclusion, efflux transport mediated by MRP2 and BCRP, but not P-gp, shifts sulfasalazine permeability from high to low, thereby enabling its colonic targeting and therapeutic action. To our knowledge, this is the first demonstration of intestinal efflux acting in favor of oral drug delivery.

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The Efficacy of Syzygium aromaticum Essential Oil in Cognitive Disorders against Manganese Chronic Exposure in Rats during Development

Notulae Scientia Biologicae ◽

10.15835/nsb629277 ◽

2014 ◽

Vol 6 (2) ◽

pp. 131-137

Author(s):

Djallal Eddine Houari ADLI ◽

Khaled KAHLOULA ◽

Miloud SLIMANI ◽

Zakia LAHOUEL ◽

Amina BELMAHI

Keyword(s):

Locomotor Activity ◽

Essential Oil ◽

Cognitive Disorders ◽

Wistar Rat ◽

Manganese Chloride ◽

Syzygium Aromaticum ◽

Protective Agent ◽

Lactation Period ◽

Rat Pups

The essential oil of Syzygium aromaticum has been widely used in traditional medicine to treat a variety of diseases, including some neurological disorders. This study aims at testing, in vivo, the possible anxiolytic and antidepressant effects, of the Syzygium aromaticum essential oil against chronic manganese chloride (4.79 mg/l) intoxication during the gestation and lactation period, in Wistar rat pups. Wistar rat pups were exposed to manganese via their dams’ drinking water from postnatal day (PND) 1 to (PND) 21. After their weaning, the rats exposed to manganese received injections of essential oil of Syzygium aromaticum (0.1 ml/kg) for 18 days. The level of anxiety, depression and locomotor activity were studied. Locomotor activity (open field test), anxiety (elevated plus maze tests), and depression (forced swimming test) were evaluated. The results of the present study indicate that Manganese exposure induces, on the one hand, impairments of body (p<0.001) and of brain weight (p<0.05). On the other hand, it increases level of anxiety (p<0.05), depression (p<0.001) and locomotor hyporactivity (p<0.001), when compared to control rats. Administration of essential oil of Syzygium aromaticum leads to a reduction in the level of anxiety (p<0.05), of depression (p<0.001) and corrects locomotor hyporactivity (p<0.05) in rats exposed to manganese beforehand. These results suggest that essential oil of Syzygium aromaticum can employ as a natural, protective agent against neuro-toxicity induced by manganese chloride during the gestation and lactation periods.

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Costal Cartilages Overgrowth Doesn’t Induce the Deformation of the Chest Wall in Experimental Animals

10.21203/rs.3.rs-136386/v1 ◽

2020 ◽

Author(s):

Vlad David ◽

Maria Stanciulescu ◽

Florin Horhat ◽

Sharma Abhinav ◽

Nilima Kundnani ◽

...

Keyword(s):

Chest Wall ◽

Model Material ◽

Cellular Growth ◽

Dependent Manner ◽

Control Groups ◽

Insulin Growth Factor ◽

Rat Pups ◽

And Control ◽

Dose Dependent

Abstract Introduction: Many consider overgrowth of the costal cartilages to be the etiological factor for chest wall deformities in children. The aim of this study is to investigate if induced overgrowth of the costal cartilages leads to the deformation of the chest wall in an animal model. Material and Methods: We injected insulin growth factor 1 (IGF1) solution directly under the perichondrium of the last three costal cartilages of rat pups. We used two different concentrations: 50 μg/ml (E50) and 100 μg/ml (E100). The procedure was repeated once per week for five consecutive weeks. Seven days from the last administration of injections, the animals were euthanized. We assessed the shape and measured the diameters of the thoracic cage. The last three costal cartilages were dissected; the samples were prepared and examined in light microscopy. Results: In E100 the sagittal and coronal diameters of the rib cage were larger than E50 and control groups but without any deformation of the chest wall. The microscopic examinations revealed an anabolic pattern in E100.Conclusion: Locally administered IGF1 stimulates, in a dose dependent manner, in-vivo cellular growth and multiplication in the costal cartilages. The induced overgrowth of the costal cartilages however, didn’t result in the deformation of the chest wall.

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Cardiomyocytes Bind and Activate Renal But not Non-Renal Human Prorenin.

Hypertension ◽

10.1161/hyp.36.suppl_1.694 ◽

2000 ◽

Vol 36 (suppl_1) ◽

pp. 694-694

Author(s):

Jasper J Saris ◽

Frans HM Derkx ◽

Pramod R Saxena ◽

Jos MJ Lamers ◽

Maarten ADH Schalekamp ◽

...

Keyword(s):

Amniotic Fluid ◽

Renal Artery ◽

Wistar Rat ◽

Dependent Manner ◽

Enzyme Kinetic ◽

Human Amniotic Fluid ◽

Kinetic Assay ◽

Enzymatic Dissociation ◽

Rat Pups ◽

Final Volume

P10 Cardiomyocytes bind and internalize recombinant human prorenin (rhPR) and renin via mannose 6-phosphate (M6P) receptors (van Kesteren et al., Hypertension 1997). PR binding is followed by intracellular activation. Here we investigated 1) whether cardiomyocytes bind native human (pro)renin ((P)R) from various sources and 2) whether PR binding is followed by activation. Myocytes were isolated from Wistar rat pups by enzymatic dissociation and grown to confluence (6 x 10 5 cells in 3.8 cm 2 wells). Cells were incubated with rhPR, human plasma (obtained from captopril-treated patients (CAP), patients with renal artery stenosis (RAS) and anephric subjects (Nx)), or human amniotic fluid (HAF), diluted in DMEM (final volume 0.4 mL), for 4 hrs at 37°C, either with or without 10 mM M6P. Cell-associated R and PR, the latter following prior activation by plasmin, were determined by enzyme-kinetic assay. Results: See Table. Intracellular PR activation is reflected by the higher R/PR ratio in the cell lysates as compared to the medium. Conclusions: Cardiomyocytes bind and activate native human PR from renal (CAP & RAS), but not from non-renal (Nx & HAF) sources in a M6P- dependent manner. These data suggest that renal PR is meant to be sequestered by nonrenin-producing tissues in order to contribute to local angiotensin production, whereas non-renal PR functions at its production site only.

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Role of pups' ultrasonic calls in a particular maternal behavior in Wistar rat: pups' anogenital licking

Behavioural Brain Research ◽

10.1016/s0166-4328(05)80296-7 ◽

1992 ◽

Vol 50 (1-2) ◽

pp. 147-154 ◽

Cited By ~ 65

Author(s):

I. Brouette-Lahlou ◽

E. Vernet-Maury ◽

M. Vigouroux

Keyword(s):

Maternal Behavior ◽

Wistar Rat ◽

Rat Pups ◽

Ultrasonic Calls

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Effects of NO-Donors on Thrombus Formation and Microcirculation in Cerebral Vessels of the Rat

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650532 ◽

1996 ◽

Vol 76 (01) ◽

pp. 111-117 ◽

Cited By ~ 10

Author(s):

Yasuto Sasaki ◽

Junji Seki ◽

John C Giddings ◽

Junichiro Yamamoto

Keyword(s):

Blood Flow ◽

Thrombus Formation ◽

Dependent Manner ◽

Red Cell ◽

Cell Velocity ◽

Red Cell Velocity ◽

The Mean ◽

Wall Shear ◽

Dose Dependent

SummarySodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1), are known to liberate nitric oxide (NO). In this study the effects of SNP and SIN-1 on thrombus formation in rat cerebral arterioles and venules in vivo were assessed using a helium-neon (He-Ne) laser. SNP infused at doses from 10 Μg/kg/h significantly inhibited thrombus formation in a dose dependent manner. This inhibition of thrombus formation was suppressed by methylene blue. SIN-1 at a dose of 100 Μg/kg/h also demonstrated a significant antithrombotic effect. Moreover, treatment with SNP increased vessel diameter in a dose dependent manner and enhanced the mean red cell velocity measured with a fiber-optic laser-Doppler anemometer microscope (FLDAM). Blood flow, calculated from the mean red cell velocity and vessel diameters was increased significantly during infusion. In contrast, mean wall shear rates in the arterioles and venules were not changed by SNP infusion. The results indicated that SNP and SIN-1 possessed potent antithrombotic activities, whilst SNP increased cerebral blood flow without changing wall shear rate. The findings suggest that the NO released by SNP and SIN-1 may be beneficial for the treatment and protection of cerebral infarction

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The Effect of Active Site-inhibited Factor VIIa on Tissue Factor-initiated Coagulation Using Platelets before and after Aspirin Administration

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657715 ◽

1997 ◽

Vol 78 (04) ◽

pp. 1202-1208 ◽

Cited By ~ 18

Author(s):

Marianne Kjalke ◽

Julie A Oliver ◽

Dougald M Monroe ◽

Maureane Hoffman ◽

Mirella Ezban ◽

...

Keyword(s):

Tissue Factor ◽

Active Site ◽

Large Scale ◽

Thrombin Generation ◽

Factor Viia ◽

Dependent Manner ◽

Antithrombotic Agent ◽

Before And After ◽

Ic50 Values

SummaryActive site-inactivated factor VIIa has potential as an antithrombotic agent. The effects of D-Phe-L-Phe-L-Arg-chloromethyl ketone-treated factor VIla (FFR-FVIIa) were evaluated in a cell-based system mimicking in vivo initiation of coagulation. FFR-FVIIa inhibited platelet activation (as measured by expression of P-selectin) and subsequent large-scale thrombin generation in a dose-dependent manner with IC50 values of 1.4 ± 0.8 nM (n = 8) and 0.9 ± 0.7 nM (n = 7), respectively. Kd for factor VIIa binding to monocytes ki for FFR-FVIIa competing with factor VIIa were similar (11.4 ± 0.8 pM and 10.6 ± 1.1 pM, respectively), showing that FFR-FVIIa binds to tissue factor in the tenase complex with the same affinity as factor VIIa. Using platelets from volunteers before and after ingestion of aspirin (1.3 g), there were no significant differences in the IC50 values of FFR-FVIIa [after aspirin ingestion, the IC50 values were 1.7 ± 0.9 nM (n = 8) for P-selectin expression, p = 0.37, and 1.4 ± 1.3 nM (n = 7) for thrombin generation, p = 0.38]. This shows that aspirin treatment of platelets does not influence the inhibition of tissue factor-initiated coagulation by FFR-FVIIa, probably because thrombin activation of platelets is not entirely dependent upon expression of thromboxane A2.

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Chickpea (Cicer arietinum L.) Lectin Exhibit Inhibition of ACE-I, α-amylase and α-glucosidase Activity

Protein and Peptide Letters ◽

10.2174/0929866526666190327130037 ◽

2019 ◽

Vol 26 (7) ◽

pp. 494-501 ◽

Cited By ~ 5

Author(s):

Sameer Suresh Bhagyawant ◽

Dakshita Tanaji Narvekar ◽

Neha Gupta ◽

Amita Bhadkaria ◽

Ajay Kumar Gautam ◽

...

Keyword(s):

Biological Effects ◽

Exchange Chromatography ◽

Health Concern ◽

Carbohydrate Binding ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Ic50 Values ◽

Chickpea Lectin

Background: Diabetes and hypertension are the major health concern and alleged to be of epidemic proportions. This has made it a numero uno subject at various levels of investigation. Glucosidase inhibitor provides the reasonable option in treatment of Diabetes Mellitus (DM) as it specifically targets post prandial hyperglycemia. The Angiotensin Converting Enzyme (ACE) plays an important role in hypertension. Therefore, inhibition of ACE in treatment of elevated blood pressure attracts special interest of the scientific community. Chickpea is a food legume and seeds contain carbohydrate binding protein- a lectin. Some of the biological properties of this lectin hitherto been elucidated. Methods: Purified by ion exchange chromatography, chickpea lectin was tested for its in vitro antioxidant, ACE-I inhibitory and anti-diabetic characteristic. Results: Lectin shows a characteristic improvement over the synthetic drugs like acarbose (oral anti-diabetic drug) and captopril (standard antihypertensive drug) when, their IC50 values are compared. Lectin significantly inhibited α-glucosidase and α-amylase in a concentration dependent manner with IC50 values of 85.41 ± 1.21 ҝg/ml and 65.05 ± 1.2 µg/ml compared to acarbose having IC50 70.20 ± 0.47 value of µg/ml and 50.52 ± 1.01 µg/ml respectively. β-Carotene bleaching assay showed antioxidant activity of lectin (72.3%) to be as active as Butylated Hydroxylanisole (BHA). In addition, lectin demonstrated inhibition against ACE-I with IC50 value of 57.43 ± 1.20 µg/ml compared to captopril. Conclusion: Lectin demonstrated its antioxidant character, ACE-I inhibition and significantly inhibitory for α-glucosidase and α-amylase seems to qualify as an anti-hyperglycemic therapeutic molecule. The biological effects of chickpea lectin display potential for reducing the parameters of medically debilitating conditions. These characteristics however needs to be established under in vivo systems too viz. animals through to humans.

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