ALTERATION OF CYP3A1 mRNA LEVEL IN PRIMARY RAT HEPATOCYTES IN RESPONSE TO AMPK ACTIVE ATOR AICAR

Background and Objective AMP-activated protein kinase (AMPK) functions as a sensor of the intracellular energy status that can be stimulated by a synthetic activator, 5-aminoimidazole–4–carboxamide–1–beta–D–ribofuranoside (AICAR), which is used to replicate the effect of physical exercise in hepatocyte embryoid bodies. This study investigated the effect of AICAR on the CYP3A1 mRNA expression in primary hepatocyte embryoid bodies derived from a rat liver. Material and Methods The primary hepatocytes were isolated from a male Sprague Dawley (SD) rat (215 g) and subjected to the following treatments: control without AICAR (CTL, n=3), 1 μM AICAR (n=3), 10 μM AICAR (n=3), and 100 μM AICAR (n=3). RNA was isolated and used as the template for synthesizing cDNA by reverse transcriptase to perform quantitative PCR (qPCR). The independent samples t-test was conducted to examine differences between groups. Statistical significance was set at p<0.05. Results The qPCR analysis demonstrated that CYP3A1 mRNA expression in primary hepatocyte embryoid bodies significantly increased in the presence of 10 μM (t=1.730, p<0.05) and 100 μM AICAR (t=3.207, p<0.05) as compared to that in the control group hepatocytes. However, the observed increase of CYP3A1 mRNA in hepatocyte embryoid bodies was not statistically significant in the presence of 1 μM AICAR as the lowest test concentration. Conclusion In this study, we demonstrated that AICAR, an AMPK activator, can increase the expression of CYP3A1 mRNA in primary hepatocytes. Future studies should assess the effect of AICAR treatment on CYP3A4 in human hepatocytes.

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P3486Experimental model for heart failure in rats: apelin-13/apj and bnp-45 gene expression analysis

European Heart Journal ◽

10.1093/eurheartj/ehz745.0354 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

H R Helmi ◽

A P Sunjaya ◽

D Limanan ◽

A R Prijanti ◽

S W A Jusman ◽

...

Keyword(s):

Gene Expression ◽

Heart Failure ◽

Cardiac Hypertrophy ◽

Mrna Expression ◽

Rat Model ◽

Control Group ◽

P Value ◽

Sprague Dawley ◽

Hypoxia Exposure ◽

Systemic Hypoxia

Abstract Background Apelin, an adipokine peptide and its receptor has recently emerged as a key signaling pathway in maintaining cardiac performance at chronic pressure loads. Apelin has been linked to ventricular dysfunction and therefore maybe of pathophysiologic relevance as a candidate biomarker in HF patients. Purpose This study aims to investigate Apelin-13 gene expression and level, and Apelin receptor (APJ) level in a rat model of heart failure induced by chronic systemic hypoxia and their correlation to BNP-45 gene expression and level, the current gold standard biomarker for heart failure, and to cardiac histopathologic changes. The effect of chronic systemic hypoxia on cardiac hypertrophy, remodeling and heart failure parameters is also of interest. Methods Twenty-eight male Sprague-Dawley rats (8–12 weeks of age) were placed in special hypoxic chambers divided into 7 groups – a control group provided with normoxia (atmospheric O2 levels) and 6 exposure groups exposed to hypoxia (8% O2) for 6 hours, 1, 3, 5, 7 and 14 days respectively prior to measurement. Changes in the expression of Apelin and BNP-45 were measured using quantitative real-time PCR, whereas changes in Apelin-13, APJ and BNP-45 levels were measured using ELISA. Histopathology staining using Hematoxylin and Eosin was performed on cardiac tissues post-termination. Results Compared to control, BNP-45 mRNA expression in the hypoxic heart was only significantly different in day 14, whereas, Apelin mRNA expression had showed significantly higher values starting from day 7 onward. This is in line with the evidence of cardiac hypertrophy based on histopathologic examination present from day 7 onwards. BNP-45 and Apelin-13 levels were significantly higher compared to control from day 5 onwards with a peak on day 7. Although significantly higher than control, Apelin-13 and BNP-45 level decreases in day 14 as compared to day 7. Mean APJ levels showed a similar profile with Apelin-13 and BNP-45 levels with a peak in day 7 (4.619 ng/mL). The cardiac Apelin-13 level shows strong significant correlation with BNP-45 levels (r 0.823, p-value 0.0001). There was also a strong significant correlation between APJ receptor levels with Apelin-13 (r 0.9029, p-value 0.001) and BNP-45 (r 0.9062, p-value 0.0009) levels. Apelin-13, APJ and BNP-45 levels also showed strong significant positive correlation to the duration of hypoxia exposure. Conclusion Chronic (≥5 days) and not acute systemic hypoxia in an experimental rat model leads to increase in Apelin-13, APJ and BNP-45 levels. Apelin-13 and BNP-45 were found to significantly increase from 5 days onwards. Apelin mRNA expression was found to show significant increase earlier compared to BNP-45 mRNA expression. Hence, Apelin may serve as a new candidate biomarker for detection of HF due to oxidative stress compared to BNP-45. Exposure to chronic systemic hypoxia can serve as an easily replicable rat model for heart failure. Acknowledgement/Funding Department of Biochemistry and Molecular Biology, Faculty of Medicine, Tarumanagara University, Jakarta, Indonesia

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Does Human Amnion Membrane Prevent Postoperative Abdominal Adhesions?

The American Surgeon ◽

10.1177/0003134820939939 ◽

2020 ◽

Vol 86 (8) ◽

pp. 1038-1042

Author(s):

Hannah M. Nemec ◽

Hany Atalah ◽

Melissa Kling ◽

Larry Nichols ◽

Bowen Powers ◽

...

Keyword(s):

Abdominal Surgery ◽

Statistical Significance ◽

Adhesion Formation ◽

Scar Tissue ◽

Control Group ◽

Sprague Dawley ◽

Ongoing Research ◽

Human Amnion ◽

Treatment Groups ◽

Tissue Matrix

Background Adhesions are bands of tissue that form postoperatively after intra-abdominal surgery. Adhesions cause significant morbidity and despite ongoing research no agent or method has been shown to completely prevent adhesions. Human amnion-derived matrix is a complex tissue matrix derived from human placenta and has been used in other areas of surgery to promote healing and decrease scar tissue formation. Our hypothesis was that aerosolized human amnion-derived matrix particulate solution (HAMPS) applied during abdominal surgery would decrease adhesion formation in rats. Methods Twenty-four Sprague-Dawley rats were divided into 4 different groups. Group 1 was the control group (CG) which had cecal abrasion 20× with a surgical rasp to generate the adhesion model. Groups 2-4 were the treatment groups (TGs) and had cecal abrasion plus application of the HAMPS at concentrations of 6.25, 12.5, and 25 mg/cc, respectively. After 30 days, rats were euthanized and adhesion assessment performed. Results In all groups there were minimal adhesions noted at necropsy. Moderate inflammation was 33% in CG versus 11% in combined TGs. Average adhesion was 1.00 in CG versus 0.44 in combined TGs. This indicated an observational improvement in adhesions/inflammation in the TGs, although this did not reach statistical significance. There was a trend toward significance in the 12.5 mg/cc group alone ( P = .054). Conclusion Overall, HAMPS showed an observational decrease in adhesions in TGs although not statistically significant. There was a trend toward significance in the 12.5 mg group. Additional studies will have to be performed to further evaluate this subgroup.

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Effects of danshensu on the transforming growth factor-β1/smads signaling pathway in rats with lung injury

Materials Express ◽

10.1166/mex.2020.1824 ◽

2020 ◽

Vol 10 (11) ◽

pp. 1816-1823

Author(s):

Jing Qin ◽

Xiaoqiang Zhang ◽

Shengyan Wang ◽

Yongming Zhang

Keyword(s):

Lung Injury ◽

Mrna Expression ◽

Transforming Growth Factor ◽

Interstitial Fibrosis ◽

Abdominal Cavity ◽

Physiological Saline ◽

Transforming Growth Factor Β1 ◽

Control Group ◽

Sprague Dawley ◽

Sd Rats

Observe the therapeutic effect of Danshensu on lung injury for rats, as well as explore the mechanism of Danshensu in TGF-β1/Smads signaling. Thirty Sprague-Dawley (SD) rats were intratracheally instilled with bleomycin to induce lung injury and interstitial fibrosis. Divided Thirty rats into three groups. DA group (η = 10): Inject 15 mg/kg Danshensu into the abdominal cavity; DXM group (η = 10): Inject 1 mg/kg dexamethasone into the abdominal cavity; BLM group (η = 10): Inject 2 mL physiological saline into the abdominal cavity. Then ten SD rats were intratracheally instilled with physiological saline as normal control group, NC group: Inject 2 mL physiological saline into the abdominal cavity. After a period of 28 days, the degree of pulmonary alveolitis was evaluated using hematoxylin-eosin (HE) staining, and the degree of lung fibrosis was evaluated using Masson?s trichrome (MT) staining. The immunohistochemistry was used to determine the expression of α-SMA. Magnetic nanoparticles+rtQ-PCR was used to determine the mRNA expressions for TGF-β1, Smad3, and Smad7. The alveolitis and pulmonary fibrosis in DA rats were obviously less than those in BLM rats and DXM rats. The expression of α-SMA in DA rats was obviously less than that of in BLM rats and DXM rats; the mRNA expression of TGF-β1 and Smad3 in DA rats were obviously reduced; the Smad7 mRNA expression was obviously up-regulated. DA can alleviate rat lung injury caused by bleomycin. Inhibiting the TGF-β1 and Smad3 mRNA expression, as well as boosting the Smad7 mRNA expression is one of the mechanisms by which Danshensu reduces lung injury.

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Effects of tiletamine-xylazine-tramadol combination and its specific antagonist on AMPK in the brain of rats

Journal of Veterinary Research ◽

10.2478/jvetres-2019-0027 ◽

2019 ◽

Vol 63 (2) ◽

pp. 285-292

Author(s):

Ning Ma ◽

Xin Li ◽

Hong-bin Wang ◽

Li Gao ◽

Jian-hua Xiao

Keyword(s):

Mrna Expression ◽

Opposite Effect ◽

Brain Regions ◽

Control Group ◽

Sprague Dawley ◽

Sd Rats ◽

The Central Nervous System ◽

Specific Antagonist ◽

Sedation And Analgesia ◽

The Brain

AbstractIntroduction:Tiletamine-xylazine-tramadol (XFM) has few side effects and can provide good sedation and analgesia. Adenosine 5’-monophosphate-activated protein kinase (AMPK) can attenuate trigeminal neuralgia. The study aimed to investigate the effects of XFM and its specific antagonist on AMPK in different regions of the brain.Material and Methods:A model of XFM in the rat was established. A total of 72 Sprague Dawley (SD) rats were randomly divided into three equally sized groups: XFM anaesthesia (M group), antagonist (W group), and XFM with antagonist interactive groups (MW group). Eighteen SD rats were in the control group and were injected intraperitoneally with saline (C group). The rats were sacrificed and the cerebral cortex, cerebellum, hippocampus, thalamus, and brain stem were immediately separated, in order to detect AMPKα mRNA expression by quantitative PCR.Results:XFM was able to increase the mRNA expression of AMPKα1 and AMPKα2 in all brain regions, and the antagonist caused the opposite effect, although the effects of XFM could not be completely reversed in some areas.Conclusion:XFM can influence the expression of AMPK in the central nervous system of the rat, which can provide a reference for the future development of anaesthetics for animals.

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Anti-inflammatory activity of palmitoylethanolamide ameliorates osteoarthritis induced by monosodium iodoacetate in Sprague–Dawley rats

Inflammopharmacology ◽

10.1007/s10787-021-00870-3 ◽

2021 ◽

Vol 29 (5) ◽

pp. 1475-1486

Author(s):

Jae In Jung ◽

Hyun Sook Lee ◽

Young Eun Jeon ◽

So Mi Kim ◽

Su Hee Hong ◽

...

Keyword(s):

Mrna Expression ◽

Acid Amide ◽

Treatment Strategies ◽

Leukotriene B4 ◽

Control Group ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Tnf Α ◽

Monosodium Iodoacetate ◽

Anti Inflammatory

AbstractNovel treatment strategies are urgently required for osteoarthritis (OA). Palmitoylethanolamide (PEA) is a naturally occurring fatty acid amide with analgesic and anti-inflammatory effects. We aimed to examine its effect on OA and elucidate the molecular mechanism of actions in monosodium iodoacetate (MIA)-induced OA Sprague–Dawley rats. The experimental animals were divided into normal control group (injected with saline + treated with phosphate-buffered saline (PBS), NOR), control group (injected with MIA + treated with PBS, CON), 50 or 100 mg/kg body weight (BW)/day PEA-treated group (injected with MIA + treated with 50 or 100 mg of PEA/kg BW/day, PEA50 or PEA100), and positive control group (injected with MIA + treated with 6 mg of diclofenac/kg BW/day, DiC). The changes in blood parameters, body parameters, gene expression of inflammatory mediators and cytokines, knee thickness, and joint tissue were observed. Oral administration of PEA had no adverse effects on the BW, liver, or kidneys. PEA reduced knee joint swelling and cartilage degradation in MIA-induced OA rats. The serum levels of leukotriene B4, nitric oxide, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and prostaglandin E2 considerably reduced in the PEA100 group compared with those in the CON group. In the synovia of knee joints, the mRNA expression of iNOS, 5-Lox, Cox-2, Il-1β, Tnf-α, and Mmp-2, -3, -9, and -13 apparently increased with MIA administration. Meanwhile, Timp-1 mRNA expression apparently decreased in the CON group but increased to the normal level with PEA treatment. Thus, PEA can be an effective therapeutic agent for OA.

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S207. CHRONIC TREATMENT WITH 1METIQ INDUCES PRO-COGNITIVE EFFECT ON RECOGNITION MEMORY IN KETAMINE MODEL OF SCHIZOPHRENIA IN RATS

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa031.273 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S117-S117

Author(s):

Magdalena Białoń ◽

Agnieszka Wąsik ◽

Marcelina Żarnowska

Keyword(s):

Recognition Memory ◽

Glutamate Release ◽

Statistical Significance ◽

Memory Function ◽

Memory Deficits ◽

Mammalian Brain ◽

Control Group ◽

World Population ◽

Sprague Dawley ◽

Cognitive Effect

Abstract Background Schizophrenia is severe mental disorder that affects 1% of world population and cause long-term disability (Mueser and McGurk, 2004). Manifestation of the illness can be distinguished into three groups – positive, negative and cognitive symptoms (van Os, 2009). However, cognitive ones (e.g. memory deficits) seem to remain resistant to pharmacotherapy (Cerveri et al., 2019). Memory deficits, as a symptoms of schizophrenia, may be modeled in animals by using a specified dose of ketamine and measured in novel object recognition (NOR) test (Lafionatis et al., 2019). 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) is an endogenous amine present and synthesized in the mammalian brain with neuroprotective properties (Antkiewicz-Michaluk et al., 2014) and our last study have shown anxiolytic action of 1MeTIQ in rat model of schizophrenia (Wąsik et al., 2019) therefore we decided to define a potential of 1MeTIQ to exhibit pro-cognitive effect on memory in ketamine-treated rats. Methods NOR test consisted of adaptation (24h before testing) and two phases (T1 and T2, with 1-hour interval). Exploration times of each objects, preference (PI) and discrimination (DI) indexes were measured. Microdialysis was performed to asses glutamate release in frontal cortex. Male Sprague Dawley rats were divided into 4 groups. The control group received saline injections. Animals received acute ketamine (20mg/kg, i.p.) or chronic (7x) administration of1MeTIQ (50mg/kg, i.p.). The combined group received single dose of ketamine 30 minutes after last dose of 1MeTIQ. Results In T1 phase of NOR, there were no changes between exploration times of two identical objects. In T2 phase with two different objects, we observed no significant changes in group treated with ketamine. 1MeTIQ given alone increased the difference between time of objects exploration. In combined group, 1MeTIQ completely reversed the effect of ketamine. Ketamine tended, however, without statistical significance, to decrease PI and DI. Treatment with 1MeTIQ did not change mentioned indexes. In microdialysis study, we observed no significant changes in glutamate release in any group. Discussion We demonstrated that chronic administration of 1MeTIQ may improve recognition memory function. However, we didn’t observe changes in glutamate release. We suggest that pro-cognitive effect of 1MeTIQ is associated with its impact on monoamine metabolism.

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Gold Nanoparticles with Dexmedetomidine Regulate GSK-3β to Reduce Neurocognitive Effects in Anesthetized Rats

Journal of Nanoscience and Nanotechnology ◽

10.1166/jnn.2021.18745 ◽

2021 ◽

Vol 21 (12) ◽

pp. 6205-6211

Author(s):

Xiaoxia Zhang ◽

Zumin Xing ◽

Jiyuan Li ◽

Shuyi Tang ◽

Yiwen Zhang

Keyword(s):

Gold Nanoparticles ◽

Mrna Expression ◽

Intraperitoneal Injection ◽

Control Group ◽

Sprague Dawley ◽

Rt Pcr ◽

Anesthetized Rats ◽

Sprague Dawley Rats ◽

Gsk 3Β ◽

Neurocognitive Effect

The aim of this study was to explore the neurocognitive effects of dexmedetomidine-loaded gold nanoparticles (AuNPs-dexmedetomidine) on anesthetized rats. Sixty Sprague Dawley rats (age, 2–3 weeks; weight, 250–280 g) were randomly divided into three groups (n = 20): the control group and two groups that received intraperitoneal injection of AuNPs-dexmedetomidine at 50 and 100 μg/kg each. Western blotting and RT-PCR were used to determine the protein and mRNA expression of GSK-3β, respectively. Compared with that in the control group, GSK-3β expression in AuNP-dexmedetomidine groups increased (P < 0.05). The protein expression of GSK-3β was higher and mRNA expression was significantly lower in the 100 μg/kg AuNP-dexmedetomidine group (P < 0.05). AuNPs-dexmedetomidine reduced the neurocognitive effect on anesthetized rats through the regulation of the GSK-3β signaling pathway.

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mRNA Expression of CYP2E1, CYP2A19, CYP1A2, HSD3B, SULT1A1 and SULT2A1 genes in surgically castrated, immunologically castrated, entire male and female pigs and correlation with androstenone, skatole, indole and Improvac-specific antibody levels

Czech Journal of Animal Science ◽

10.17221/159/2018-cjas ◽

2019 ◽

Vol 64 (No. 2) ◽

pp. 89-97

Author(s):

A. Kubešová ◽

K. Šťastný ◽

M. Faldyna ◽

Z. Sládek ◽

I. Steinhauserová ◽

...

Keyword(s):

Gene Expression ◽

Mrna Expression ◽

Mrna Level ◽

Boar Taint ◽

Control Group ◽

Mrna Levels ◽

Large White ◽

Specific Antibodies ◽

Significant Difference ◽

Entire Male

This study aimed to obtain a comprehensive look at the influence of castration on mRNA expression of the genes CYP2E1, CYP1A2, CYP2A19, HSD3B, SULT2A1 and SULT1A1 and their correlation with boar taint compounds (androstenone, skatole and indole) and Improvac-specific antibodies in a Czech commercial hybrid (Large White × Landrace (sow) × Duroc (boar)). Pigs were divided into groups of entire male pigs (NC), pigs castrated surgically (SC), pigs immunologically castrated and slaughtered 8 weeks (IM8) or 15 weeks (IM15) after the second dose of Improvac, and gilts (GI). Hepatic mRNA expression, measured by quantitative real-time polymerase chain reaction, differed significantly between the control group (entire male pigs) and all groups of interest for CYP2E1, CYP1A2 and CYP2A19. The mRNA level of the HSD3B gene differed significantly between the control group and the IM8, IM15 and GI groups. SULT1A1 gene expression was significantly different between the control group and the SC, IM8 and GI. In the case of SULT2A1, a significant difference was observed only between the control group and IM8 pigs. For all genes and treatment groups described above, expression was increased relative to the control. Significant differences for Improvac-specific antibodies between IM8 and IM15 groups were observed, indicating decrease of antibodies over time. Moreover, negative correlations between androstenone and mRNA levels of CYP2A19, CYP2E1 and SULT1A1 suggest that gene expression is suppressed.

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Effect of the Phragmitis Rhizoma Aqueous Extract on the Pharmacokinetics of Docetaxel in Rats

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207322666190419110724 ◽

2019 ◽

Vol 22 (5) ◽

pp. 326-332

Author(s):

Sarah Shin ◽

No Soo Kim ◽

Young Ah Kim ◽

Hea Ry Oh ◽

Ok-Sun Bang

Keyword(s):

Aqueous Extract ◽

Statistical Significance ◽

Ultra Performance Liquid Chromatography ◽

Pharmacokinetic Parameters ◽

Control Group ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Liquid Chromatography Tandem Mass ◽

Mass Spectrometry System ◽

Phragmitis Rhizoma

Background: Traditionally, Phragmitis rhizoma has been prescribed to relive a fever, vomiting, dysuria, and constipation, and to promote secretion of fluids. In addition, recent studies have reported its efficacy as a diuretic and antiemetic. Our previous study demonstrated that the Phragmitis rhizoma aqueous extract (EPR) ameliorates docetaxel (DTX)-induced myelotoxicity. Aim and Objective: This study was aimed to investigate the effects of EPR on the pharmacokinetics of DTX in Sprague–Dawley rats. Materials & Methods: The animals received an intravenous injection of DTX (5 mg/kg) with or without oral EPR (100 mg/kg) pretreatment for 1 or 6 days. The pharmacokinetics of plasma DTX was analyzed using an ultra-performance liquid chromatography-tandem mass spectrometry system, and pharmacokinetic parameters were estimated via noncompartmental analysis. Results: Relative to the control group (DTX alone), EPR pretreatment did not affect significantly the overall profiles of plasma DTX levels. Consecutively pretreated EPR for 6 days slightly altered AUC0-t and Cmax of DTX by 122 and 145.9%, respectively, but these data did not reach the threshold of statistical significance (p > 0.05). Conclusion: These results indicate that DTX exposure may not be affected by EPR treatment at the dose level used in this study, suggesting that oral EPR can be used safely when taken with intravenously injected DTX. However, further studies under the stringent conditions are needed when chronic treatment of EPR and anticancer drug.

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Modulatory effect of olanzapine on SMIM20/phoenixin, NPQ/spexin and NUCB2/nesfatin-1 gene expressions in the rat brainstem

Pharmacological Reports ◽

10.1007/s43440-021-00267-7 ◽

2021 ◽

Author(s):

Artur Pałasz ◽

Piotr Żarczyński ◽

Katarzyna Bogus ◽

Kinga Mordecka-Chamera ◽

Alessandra Della Vecchia ◽

...

Keyword(s):

Gene Expression ◽

Mrna Expression ◽

Mrna Level ◽

Brain Structures ◽

Term Treatment ◽

Sprague Dawley ◽

Gene Expressions ◽

Alternative Mode ◽

Long Term Treatment ◽

Rat Brainstem

Abstract Background Phoenixin, spexin and nesfatin-1 belong to a family of newly discovered multifunctional neuropeptides that play regulatory roles in several brain structures and modulate the activity of important neural networks. However, little is known about their expression and action at the level of brainstem. The present work was, therefore, focused on gene expression of the aforementioned peptides in the brainstem of rats chronically treated with olanzapine, a second generation antipsychotic drug. Methods Studies were carried out on adult, male Sprague–Dawley rats that were divided into 2 groups: control and experimental animals treated with olanzapine (28-day-long intraperitoneal injection, at dose 5 mg/kg daily). All individuals were killed under anesthesia and the brainstem excised. Total mRNA was isolated from homogenized samples of both structures and the RT-PCR method was used for estimation of related SMIM20/phoenixin, NPQ/spexin and NUCB2/nesfatin-1 gene expression. Results Long-term treatment with olanzapine is reflected in qualitatively different changes in expression of examined neuropeptides mRNA in the rat brainstem. Olanzapine significantly decreased NPQ/spexin mRNA expression, but increased SMIM20/phoenixin mRNA level in the rat brainstem; while NUCB2/nesfatin-1 mRNA expression remained unchanged. Conclusions Olanzapine can affect novel peptidergic signaling in the rat brainstem. This may cautiously suggest the presence of an alternative mode of its action.

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