Effects of psoralen on hepatic bile acid transporters in rats

2020 ◽  
pp. 096032712097934
Author(s):  
Juyang Huang ◽  
Qin Wang ◽  
Mengying Chen ◽  
Yanan Bi ◽  
Hong Shi ◽  
...  
Keyword(s):  
Bile Acid ◽  
Weight Ratio ◽  
Sprague Dawley ◽  
Body Weight Ratio ◽  
Hepatic Bile ◽  
Tissue Samples ◽  
Protein Levels ◽  
Bile Acid Transporters ◽  
Sprague Dawley Rats ◽  
Underlying Mechanisms

Fructus Psoraleae (FP), widely used in traditional medicine, is increasingly reported to cause serious hepatotoxicity in recent years. However, the main toxic constituents responsible for hepatotoxicity and the underlying mechanisms are poorly understood. In the present study, psoralen, a main and quality-control constituent of FP, was intragastrically administered to Sprague-Dawley rats at a dose of 60 mg/kg for 1, 3 and 7 days. Blood and selected tissue samples were collected and analyzed for biochemistry and histopathology to evaluate hepatotoxicity. The results showed that psoralen could induce hepatotoxicity by enhanced liver-to-body weight ratio and alterations of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total cholesterol after administration for 3 days. In addition, histopathological examinations also indicated the hepatotoxicity induced by psoralen. Furthermore, the mRNA and protein levels of hepatic bile acid transporters were significantly changed, in which MRP4, ABCG5 and ABCG8 were repressed, while the protein level of NTCP tended to increase in the rat liver. Taken together, psoralen caused liver injury possibly through affecting bile acid transporters, leading to the disorder of bile acid transport and accumulation in hepatocytes.

scholarly journals Aerobic Exercise Prevents Depression via Alleviating Hippocampus Injury in Chronic Stressed Depression Rats

2020 ◽  
Vol 11 (1) ◽  
pp. 9
Author(s):  
Jie Kang ◽  
Di Wang ◽  
Yongchang Duan ◽  
Lin Zhai ◽  
Lin Shi ◽  
...  
Keyword(s):  
Aerobic Exercise ◽  
Mild Stress ◽  
Glutamatergic System ◽  
Sprague Dawley ◽  
Bdnf Expression ◽  
Sprague Dawley Rats ◽  
Immobility Time ◽  
Neurotoxic Effects ◽  
Swimming Test ◽  
Underlying Mechanisms

(1) Background: Depression is one of the overwhelming public health problems. Alleviating hippocampus injury may prevent depression development. Herein, we established the chronic unpredictable mild stress (CUMS) model and aimed to investigate whether aerobic exercise (AE) could alleviate CUMS induced depression-like behaviors and hippocampus injury. (2) Methods: Forty-eight healthy male Sprague-Dawley rats (200 ± 20 g) were randomly divided into 4 groups (control, CUMS, CUMS + 7 days AE, CUMS + 14 days AE). Rats with AE treatments were subjected to 45 min treadmill per day. (3) Results: AE intervention significantly improved CUMS-induced depressive behaviors, e.g., running square numbers and immobility time assessed by the open field and forced swimming test, suppressed hippocampal neuron apoptosis, reduced levels of phosphorylation of NMDA receptor and homocysteine in hippocampus, as well as serum glucocorticoids, compared to the CUMS rats. In contrast, AE upregulated phosphorylation of AMPAR receptor and brain-derived neurotrophic factor (BDNF) hippocampus in CUMS depression rats. The 14 day-AE treatment exhibited better performance than 7 day-AE on the improvement of the hippocampal function. (4) Conclusion: AE might be an efficient strategy for prevention of CUMS-induced depression via ameliorating hippocampus functions. Underlying mechanisms may be related with glutamatergic system, the neurotoxic effects of homocysteine, and/or influences in glucocorticoids-BDNF expression interaction.

Curcumin Reduces Neuroinflammation and Improves the Impairments of Anesthetics on Learning and Memory by Regulating the Expression of miR-181a-5p

2021 ◽  
pp. 1-9
Author(s):  
Guizhen Liu ◽  
Yuchuan Sun ◽  
Fei Liu
Keyword(s):  
Cognitive Impairment ◽  
Protective Effect ◽  
Learning And Memory ◽  
Cognitive Dysfunction ◽  
Inflammatory Cytokines ◽  
Neuroprotective Effect ◽  
Morris Water Maze Test ◽  
Sprague Dawley ◽  
Protein Levels ◽  
Sprague Dawley Rats

<b><i>Objective:</i></b> The purpose of this study was to explore the role of curcumin (Cur) in isoflurane (ISO)-induced learning and memory dysfunction in Sprague-Dawley rats and further elucidate the mechanism of the protective effect produced by Cur. <b><i>Methods:</i></b> Rat models of cognitive impairment were established by inhaling 3% ISO. The Morris water maze test was used to assess the cognitive function of rats. ELISA and qRT-PCR were used to analyze the protein levels of pro-inflammatory cytokines and expression levels of miR-181a-5p, respectively. <b><i>Results:</i></b> Cur significantly improved the ISO-induced cognitive dysfunction in rats and alleviated the ISO-induced neuroinflammation. miR-181a-5p was overexpressed in ISO-induced rats, while Cur treatment significantly reduced the expression of miR-181a-5p. Overexpression of miR-181a-5p promoted the cognitive impairment and the release of inflammatory cytokines and reversed the neuroprotective effect of Cur. <b><i>Conclusion:</i></b> Cur has a protective effect on ISO-induced cognitive dysfunction, which may be achieved by regulating the expression of miR-181a-5p.

Changes in rat mesentery interstitial matrix due to superfusate

1993 ◽  
Vol 265 (3) ◽  
pp. H852-H856 ◽  
Author(s):  
B. J. Barber ◽  
R. A. Babbitt ◽  
S. Dutta ◽  
S. Parameswaran
Keyword(s):  
Protein Content ◽  
Normal Saline ◽  
Protein Concentration ◽  
Matrix Protein ◽  
Protein Transport ◽  
Albumin Concentration ◽  
Sprague Dawley ◽  
Tissue Samples ◽  
Rat Mesentery ◽  
Sprague Dawley Rats

Animal preparations for microscopy often require a superfusate solution to cover surgically exposed tissue. There are few, if any, data concerning the effects of this solution on extravascular protein concentration and hydration. The effect of superfusion on mesenteric tissue in anesthetized male Sprague-Dawley rats was studied. Tissue samples were taken from nonsuperfused and superfused tissue and analyzed for hydration, albumin, and transferrin content. The mesenteric tissue interstitial matrix was rapidly altered by normal saline superfusate. After superfusion, there was a decrease (P < 0.01) in tissue albumin concentration from 1.17 +/- 0.27 to 0.10 +/- 0.08 g/dl (n = 9). Tissue hydration increased from 4.98 +/- 0.8 micrograms water/microgram dry wt in controls to 7.38 +/- 1.2 micrograms water/micrograms dry wt after superfusion. When a range of superfusate albumin concentrations was used (0, 1, 2, and 3 g/dl), tissue albumin concentration changed 0.59 +/- 0.09 g/dl for each gram per deciliter change in superfusate concentration (P < 0.0001). The large changes in interstitial matrix protein content and hydration suggest that superfusate solution effects need to be considered in microvascular protein transport experiments.

Mineralocorticoid Receptor Activation by Aldosterone or Corticosterone Induces Hypertension, Myocardial Infarction and Proteinuria

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 723-723
Author(s):  
Qing-Feng Tao ◽  
Diego Martinez vasquez ◽  
Ricardo Rocha ◽  
Gordon H Williams ◽  
Gail K Adler
Keyword(s):  
Myocardial Infarction ◽  
Drinking Water ◽  
Mineralocorticoid Receptor ◽  
Critical Role ◽  
Weight Ratio ◽  
Myocardial Necrosis ◽  
Receptor Activation ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

P165 Aldosterone through its interaction with the mineralocorticoid receptor (MR) plays a critical role in the development of hypertension and cardiovascular injury (CVI). Normally, MR is protected by 11β-hydroxysteroid dehydrogenase (11β-HSD) which inactivates glucocorticoids preventing their binding to MR. We hypothesis that if activation of MR by either aldosterone or glucocorticoids induces hypertension and CVI, then the inhibition of 11β-HSD with glycyrrhizin (GA), a natural inhibitor of 11β-HSD, should induce damage similar to that observed with aldosterone. Sprague-Dawley rats were uninephrectomized, and treated for 4 weeks with 1% NaCl (in drinking water) for the control group, 1% NaCl + aldosterone infusion (0.75 μg/h), or 1% NaCl + GA (3.5 g/l in drinking water). After 4 weeks, aldosterone and GA caused significant increases in blood pressure compared to control rats ([mean ± SEM] 211± 9, 205 ± 12, 120 ± 9 mmHg, respectively, p<0.001). Both aldosterone- and GA-treated rats had a significant increase in proteinuria (152.2 ± 8.7 and 107.7 ± 19.5 mg/d, respectively) versus controls (51.2 ± 9.5 mg/d). There was a significant increase (p<0.001) in heart to body weight ratio in the rats treated with aldosterone or GA compared with control (3.92 ± 0.10, 3.98 ± 0.88, and 3.24 ± 0.92 mg/g, respectively). Hearts of GA and aldosterone treated rats showed similar histological changes consisting of biventricular myocardial necrosis and fibrinoid necrosis of small coronary arteries and arterioles. These data suggests that in rodents activation of MR by either aldosterone or corticosterone leads to severe hypertension, vascular injury, proteinuria and myocardial infarction. Thus, 11β-HSD plays an important role in protecting the organism from injury.

Abstract 114: K+ Rich Diet During Angiotensin II Hypertension Reduces Renal Na-Cl Cotransporter and Phosphorylation, but Not Blood Pressure

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Luciana C Veiras ◽  
Jiyang Han ◽  
Donna L Ralph ◽  
Alicia A McDonough
Keyword(s):  
Blood Pressure ◽  
Urine Volume ◽  
Weight Ratio ◽  
Distal Tubule ◽  
Reduce Blood Pressure ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
K Secretion ◽  
Pressure Natriuresis

During Ang II hypertension distal tubule Na-Cl Cotransporter (NCC) abundance and its activating phosphorylation (NCCp), as well as Epithelial Na+ channels (ENaC) abundance and activating cleavage are increased 1.5-3 fold. Fasting plasma [K+] is significantly lower in Ang II hypertension (3.3 ± 0.1 mM) versus controls (4.0 ± 0.1 mM), likely secondary to ENaC stimulation driving K+ secretion. The aim of this study was to test the hypothesis that doubling dietary K+ intake during Ang II infusion will lower NCC and NCCp abundance to increase Na+ delivery to ENaC to drive K+ excretion and reduce blood pressure. Methods: Male Sprague Dawley rats (225-250 g; n= 7-9/group) were treated over 2 weeks: 1) Control 1% K diet fed (C1K); 2) Ang II infused (400 ng/kg/min) 1% K diet fed (A1K); or 3) Ang II infused 2% K diet fed (A2K). Blood pressure (BP) was determined by tail cuff, electrolytes by flame photometry and transporters’ abundance by immunoblot of cortical homogenates. Results: As previously reported, Ang II infusion increased systolic BP (from 132 ± 5 to 197 ± 4 mmHg), urine volume (UV, 2.4 fold), urine Na+ (UNaV, 1.3 fold), heart /body weight ratio (1.23 fold) and clearance of endogenous Li+ (CLi, measures fluid volume leaving the proximal tubule, from 0.26 ± 0.02 to 0.51 ± 0.01 ml/min/kg) all evidence for pressure natriuresis. A2K rats exhibited normal plasma [K+] (4.6 ± 0.1 mM, unfasted), doubled urine K+ (UKV, from 0.20 to 0.44 mmol/hr), and increased CLi (to 0.8 ± 0.1 ml/min/kg) but UV, UNaV, cardiac hypertrophy and BP were unchanged versus the A1K group. As expected, NCC, NCCpS71 and NCCpT53 abundance increased in the A1K group to 1.5 ± 0.1, 2.9 ± 0.5 and 2.8 ± 0.4 fold versus C1K, respectively. As predicted by our hypothesis, when dietary K+ was doubled (A2K), Ang II infusion did not activate NCC, NCCpS71 nor NCCpT53 (0.91 ± 0.04, 1.3 ± 0.1 and 1.6 ± 0.2 fold versus C1K, respectively). ENaC subunit abundance and cleavage increased 1.5 to 3 fold in both A1K and A2K groups; ROMK was unaffected by Ang II or dietary K. In conclusion, evidence is presented that stimulation of NCC during Ang II hypertension is secondary to K+ deficiency driven by ENaC stimulation since doubling dietary K+ prevents the activation. The results also indicate that elevation in BP is independent of NCC activation

scholarly journals Dexamethasone Suppressed LPS-Induced Matrix Metalloproteinase and Its Effect on Endothelial Glycocalyx Shedding

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Na Cui ◽  
Hao Wang ◽  
Yun Long ◽  
Longxiang Su ◽  
Dawei Liu
Keyword(s):  
Escherichia Coli ◽  
Vascular Endothelium ◽  
Free Water ◽  
Endothelial Glycocalyx ◽  
Sprague Dawley ◽  
Treatment Groups ◽  
Protein Levels ◽  
Sprague Dawley Rats ◽  
The Matrix ◽  
Rat Thoracic Aorta

The aim of this study is to determine the mechanism of sepsis-induced vascular hyperpermeability and the beneficial effect of glucocorticoid in protecting vascular endothelium. Male Sprague-Dawley rats were given either a bolus intraperitoneal injection of a nonlethal dose of LPS (Escherichia coli055:B5, 10 mg/kg, Sigma) or vehicle (pyrogen-free water). Animals of treatment groups were also given either dexamethasone (4 mg/kg, 30 min prior to LPS injection) or the matrix metalloproteinases (MMPs) inhibitor doxycycline (4 mg/kg, 30 min after LPS injection). Both activities and protein levels of MMP-2p<0.001and MMP-9p<0.001were significantly upregulated in aortic homogenates from LPS-treated rats, associated with decreased ZO-1p<0.001and syndecan-1p=0.011protein contents. Both dexamethasone and doxycycline could significantly inhibit MMPs activity and reserve the expressions of ZO-1 and syndecan-1. The inhibition of MMPs by dexamethasone was significantly lower than that by doxycycline, while the rescue of syndecan-1 expression from LPS-induced endotoxemic rat thoracic aorta was significantly higher in the dexamethasone-treated compared to the doxycycline-treatedp=0.03. In conclusion, activation of MMPs plays important role in regulating ZO-1 and syndecan-1 protein levels in LPS mediated endothelial perturbation. Both dexamethasone and doxycycline inhibit activation of MMPs that may contribute to the rescue of ZO-1 and syndecan-1 expression.

Carvacrol attenuates amikacin-induced nephrotoxicity in the rat

2021 ◽  
Author(s):  
Atta Mohammad Dost ◽  
Mehmet Gunata ◽  
Onural Ozhan ◽  
Azibe Yildiz ◽  
Nigar Vardi ◽  
...  
Keyword(s):  
Inflammatory Cell ◽  
Kidney Tissue ◽  
Control Group ◽  
Histopathological Changes ◽  
Sprague Dawley ◽  
Tissue Samples ◽  
Sprague Dawley Rats ◽  
Before And After ◽  
Per Oral

Abstract Amikacin (AK) is frequently used in the treatment of gram-negative and some gram-positive infections. However, its use is limited due to nephrotoxicity due to the increase in reactive oxygen radicals. The aim of this study was to investigate the role of carvacrol (CAR) against AK-induced nephrotoxicity in rats. Thirty-two Sprague Dawley rats were randomly divided into four groups as control (Vehicle), AK (400 mg/kg), CAR + AK (80 mg/kg CAR + 400 mg/kg AK), and AK + CAR (400 mg/kg AK + 80 mg/kg CAR) groups. AK and CAR were administered via intramuscular and per-oral for 7 days, respectively. Blood and kidney tissue samples were taken at the end of the experiment. Renal function and histopathological changes were compared, and the relevant parameters of oxidative stress and inflammation were detected. Histopathological findings (necrotic changes and dilatation and inflammatory cell infiltration) significantly increased in the AK group compared to the control group. Also, the rats in the AK group lost weight significantly. It was found that CAR treatment before and after AK significantly improved nephrotoxicity histopathologically (p < 0.05). However, this improvement was not detected biochemically. These results show that CAR treatment before and after AK improves nephrotoxicity in the histopathological level.

The cartilage degeneration in a growing rat experimental model of developmental trochlear dysplasia is associated with activation of PI3K/AKT signal pathway

2020 ◽  
Author(s):  
Wei Lin ◽  
Yike Dai ◽  
Jinghui Niu ◽  
Chongyi Fan ◽  
Xunkai Feng ◽  
...  
Keyword(s):  
Trochlear Dysplasia ◽  
Cartilage Degeneration ◽  
Signal Pathway ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Growing Rat ◽  
Polymerase Chain ◽  
Underlying Mechanisms ◽  
Experimental Group

Abstract Background As one of the lower extremity deformities in human, trochlear dysplasia is a commonly encountered disease. However, the molecular mechanism of cartilage degeneration in trochlear dysplasia is indefinite yet. It was apparent to all that PI3K/AKT signal pathway is extremely significant in regulating the pathophysiological process of cartilage degeneration. The purpose of this research is to discuss the correlation between PI3K/AKT signal pathway and trochlear dysplasia cartilage degeneration. Materials and methods 120 female Sprague-Dawley rats at 4 weeks of age were separate into control group and experimental group randomly. The distal femurs were isolated from the experimental and unsurgeried control group at the point of the 4, 8, 12 weeks, correspondingly. Micro-CT and histological examination were carried out to investigate the anatomical structure and cartilage changes of the trochlear. Subsequently, the expression of PI3K/AKT, TGFβ1 and ADAMTS-4 in cartilage were investigated by immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR). Results In the experimental group, the trochlear dysplasia model was successfully established at 8 weeks after surgery. Moreover, the cartilage degeneration was found from 8 weeks, with continued higher protein and mRNA expression of PI3K/AKT, TGFβ1 and ADAMTS-4 compared with the control group. Conclusions This research suggested that patellar instability may lead to trochlear dysplasia in growing rats. Moreover, trochlear dysplasia was probably one of the causes of patellofemoral osteoarthritis and the cartilage degeneration in trochlear dysplasia might be associate with activation of PI3K/AKT signal pathway. However, more research was required to clarify the underlying mechanisms.

scholarly journals URI-1 Levels Are Elevated in Fatty Livers of db/db and C57BL/6 Mice Fed Trans-10, Cis-12 Conjugated Linoleic Acid

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 383-383
Author(s):  
Luis Cordero-Monroy ◽  
Carla Taylor ◽  
Peter Zahradka
Keyword(s):  
Body Weight ◽  
Fatty Acid ◽  
Linoleic Acid ◽  
Fatty Liver ◽  
Western Blotting ◽  
Weight Ratio ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
Body Weight Ratio ◽  
Protein Levels

Abstract Objectives This study was designed to investigate whether unconventional prefoldin RPB5 interactor (URI)-1 mediates hepatic accumulation of triglyceride (TG) in response to a diet with trans-10,cis-12 conjugated linoleic acid (t10,c12 CLA) in lean or genetically obese mice. URI-1 belongs to the prefoldin family of proteins that have been shown to coordinate nutrient availablility by transcriptional regulation of genes involved in glucose and lipid metabolism. Thus, it was hypothesized that URI-1 in liver is involved in increased fatty acid uptake and accumulation leading to fatty liver. Methods C57BL/6 and db/db mice were randomly assigned to two diet groups, control (CTL) and t10,c12 CLA (0.4% w/w). After 4 weeks, the mice were weighed and euthanized. Livers were dissected, weighed and stored at –80°C. Liver lysates were prepared from the tissue for Western blotting to measure hepatic protein levels of URI-1 and FABP1. The amount of lipid in the livers was determined using the LabAssay™ Triglyceride kit, a colorimetric TG assay. Results The liver to body weight ratio of db/db and C57BL/6 mice fed t10,c12 CLA increased by 90% and 52%, respectively, compared to their counterparts fed the CTL diet. Likewise, the hepatic TG concentration (mg TG/mg protein) was increased 38% and 5-fold, respectively, in CLA-fed db/db and C57BL/6 mice compared to CTL db/db and C57BL/6 mice. Western blotting showed that FABP1 levels were approximately 2-fold greater in the db/db t10,c12 CLA group relative to the db/db CTL group, and may contribute to increased fatty acid uptake. Furthermore, URI-1 protein levels were elevated 4-fold in db/db and C57BL6 mice fed t10,c12 CLA compared to their respective CTL groups. Lastly, correlation analysis revealed that URI-1 levels were significantly correlated with hepatic TG concentrations (r = 0.61) and liver/body weight ratio (r = 0.64). Conclusions This study revealed a relationship between hepatic TG accumulation and URI-1, a protein associated with hepatocellular carcinoma (HCC) and cirrhosis. This study provides a basis for in vitro experiments exploring the causative role of URI-1 in propagating hepatic TG accumulation, and ultimately the progression of fatty liver disease to HCC and cirrhosis. Funding Sources University Collaborative Research Project, NSERC Discovery, and University of Manitoba Graduate Enhancement of Tri-Council Stipends.

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