Intestinal absorption and metabolic characteristics of sildenafil: a study usingin situintestinal administration rat model based on mass fragmentation pathway

The flower bud of Daphne genkwa (Genkwa Flos) is a commonly used herbal medicine in Asian countries. Luteolin and apigenin are two recognized active flavonoids in Genkwa Flos. The aim of this study was to investigate the intestinal absorption mechanisms of Genkwa Flos flavonoids using in situ single-pass intestinal perfusion rat model. Using HPLC, we determined its major effective flavonoids luteolin, apigenin, as well as, hydroxygenkwanin and genkwanin in biological samples. The intestinal absorption mechanisms of the total flavonoids in Genkwa Flos (TFG) were investigated using in situ single-pass intestinal perfusion rat model. Comparing the TFG absorption rate in different intestinal segments, data showed that the small intestine absorption was significantly higher than that of the colon ([Formula: see text]). Compared with duodenum and ileum, the jejunum was the best small intestinal site for TFG absorption. The high TFG concentration (61.48[Formula: see text][Formula: see text]g/ml) yielded the highest permeability ([Formula: see text]). Subsequently, three membrane protein inhibitors (verapamil, pantoprazole and probenecid) were used to explore the TFG absorption pathways. Data showed probenecid, a multidrug resistance protein (or MRP) inhibitor, effectively enhanced the TFG absorption ([Formula: see text]). Furthermore, by comparing commonly used natural absorption enhancers on TFG, it was observed that camphor was the most effective. In Situ single-pass intestinal perfusion experiment shows that TFG absorption is much higher in the small intestine than in the colon, and the TFG is absorbed mainly via an active transport pathway with MRP-mediated efflux mechanism. Camphor obviously enhanced the TFG absorption, and this could be an effective TFG formulation preparation method to increase clinical effectiveness after Genkwa Flos administration. Our study elucidated the TFG absorption mechanisms, and provided new information for its formulation preparation.

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A rat model based on the histamine H2-receptor-activation-induced gastric pathology

Pharmacological Research Communications ◽

10.1016/s0031-6989(82)80098-2 ◽

1982 ◽

Vol 14 (2) ◽

pp. 175-185 ◽

Cited By ~ 5

Author(s):

P. Del Soldato ◽

A. Ghiorzi ◽

L. Buarotti

Keyword(s):

Rat Model ◽

Receptor Activation ◽

Histamine H2 Receptor ◽

H2 Receptor ◽

Gastric Pathology ◽

Model Based

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Effects of Metformin on Reproductive, Endocrine, and Metabolic Characteristics of Female Offspring in a Rat Model of Letrozole-Induced Polycystic Ovarian Syndrome With Insulin Resistance

Frontiers in Endocrinology ◽

10.3389/fendo.2021.701590 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yidong Xie ◽

Li Xiao ◽

Shangwei Li

Keyword(s):

Insulin Resistance ◽

Rat Model ◽

Polycystic Ovary ◽

Body Weight Gain ◽

Female Offspring ◽

Female Rats ◽

Metabolic Characteristics ◽

Continuous Release ◽

Reproductive Endocrine ◽

The Impact

The beneficial effects of metformin, especially its capacity to ameliorate insulin resistance (IR) in polycystic ovary syndrome (PCOS), explains why it is widely prescribed. However, its effect on the offspring of patients with PCOS remains uncertain. This study investigated the impact of metformin treatment on the first- and second-generation female offspring born to letrozole-induced PCOS-IR rats. Forty-five female Wistar rats were implanted with continuous-release letrozole pellets or placebo and treated with metformin or vehicle control. Rats exposed to letrozole showed PCOS-like reproductive, endocrine, and metabolic phenotypes in contrast to the controls. Metformin significantly decreased the risk of body weight gain and increased INSR expression in F1 female offspring in PCOS-IR rats, contributing to the improvement in obesity, hyperinsulinemia, and IR. Decreased FSHR expression and increased LHCGR expression were observed in F1 female rats of the PCOS-IR and PCOS-IR+Metformin groups, suggesting that FSHR and LHCGR dysfunction might promote the development of PCOS. Nevertheless, we found no significant differences in INSR, FSHR, and LHCGR expression or other PCOS phenotypes in F2 female offspring of PCOS-IR rats. These findings indicated widespread reproductive, endocrine, and metabolic changes in the PCOS-IR rat model, but the PCOS phenotypes could not be stably inherited by the next generations. Metformin might have contributed to the improvement in obesity, hyperinsulinemia, and IR in F1 female offspring. The results of this study could be used as a theoretical basis in support of using metformin in the treatment of PCOS-IR patients.

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Transgenerational Obesity and Alteration of ARHGEF11 in the Rat Liver Induced by Intrauterine Hyperglycemia

Journal of Diabetes Research ◽

10.1155/2019/6320839 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9

Author(s):

Wanyi Zhang ◽

Rina Su ◽

Hui Feng ◽

Li Lin ◽

Chen Wang ◽

...

Keyword(s):

Rat Model ◽

Abnormal Development ◽

Nucleotide Exchange ◽

Maternal Line ◽

Offspring Development ◽

Metabolic Characteristics ◽

Glycolipid Metabolism ◽

Obesity And Diabetes ◽

Nucleotide Exchange Factor ◽

Two Generations

It is understood that intrauterine hyperglycemia increases the risk of obesity and diabetes in offspring of consecutive generations but its mechanisms remain obscure. This study is aimed at establishing an intrauterine hyperglycemia rat model to investigate the growth and glycolipid metabolic characteristics in transgenerational offspring and discuss the effects of Rho guanine nucleotide exchange factor 11 (ARHGEF11) and the PI3K/AKT signaling pathway in offspring development. The severe intrauterine hyperglycemia rat model was caused by STZ injection before mating, while offspring development and glycolipid metabolism were observed for the following two generations. The expression of ARHGEF11, ROCK1, PI3K, and AKT was tested in the liver and muscle tissue of F2 offspring. The results showed severe growth restriction in F1 offspring and obesity, fatty liver, and insulin resistance in female F2 offspring, especially the offspring of female intrauterine hyperglycemia-exposed parents (F2G♀C♂) and both (F2G♀G♂). The expression of ARHGEF11 and ROCK1 was significantly elevated; PI3K and phosphorylation of AKT were significantly decreased in liver tissues of F2G♀C♂ and F2G♀G♂. Our study revealed that intrauterine hyperglycemia could cause obesity and abnormal glycolipid metabolism in female transgenerational offspring; the programming effect of the intrauterine environment could cause a more obvious phenotype in the maternal line. Further exploration suggested that increased expression of ARHGEF11 and ROCK1 and the decreased expression of PI3K and phosphorylation of AKT in the liver could be responsible for the abnormal development in F2 offspring.

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Developing vitamin B12 deficient rat model based on duration of restriction diet: Assessment of plasma vitamin B12, homocysteine (Hcy), and blood glucose levels

10.1063/1.5096672 ◽

2019 ◽

Author(s):

Imelda Rosalyn Sianipar ◽

Irena Ujianti ◽

Sophie Yolanda ◽

Aditya K. Murthi ◽

Patwa Amani ◽

...

Keyword(s):

Blood Glucose ◽

Vitamin B12 ◽

Rat Model ◽

Plasma Vitamin ◽

Glucose Levels ◽

Model Based ◽

Blood Glucose Levels ◽

Restriction Diet ◽

Diet Assessment

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INTRA-AXONAL MYOSIN AND ACTIN IN NERVE REGENERATION

Neurosurgery ◽

10.1227/01.neu.0000338593.76635.32 ◽

2009 ◽

Vol 65 (suppl_4) ◽

pp. A93-A96 ◽

Cited By ~ 15

Author(s):

Irvine G. McQuarrie ◽

Linda M. Lund

Keyword(s):

Sciatic Nerve ◽

Molecular Biology ◽

Nerve Regeneration ◽

Rat Model ◽

Structural Proteins ◽

Protein Chemistry ◽

Model Based ◽

Motor Enzymes ◽

Sciatic Nerve Regeneration

Abstract A FOCUSED REVIEW of sciatic nerve regeneration in the rat model, based on research conducted by the authors, is presented. We examine structural proteins carried distally in the axon by energy-requiring motor enzymes, using protein chemistry and molecular biology techniques in combination with immunohistochemistry. Relevant findings from other laboratories are cited and discussed. The general conclusion is that relatively large amounts of actin and tubulin are required to construct a regenerating axon and that these materials mainly originate in the parent axon. The motor enzymes that carry these proteins forward as macromolecules include kinesin and dynein but probably also include myosin.

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Development of a KRAS-Associated Metabolic Risk Model for Prognostic Prediction in Pancreatic Cancer

BioMed Research International ◽

10.1155/2021/9949272 ◽

2021 ◽

Vol 2021 ◽

pp. 1-21

Author(s):

Zuyi Ma ◽

Zhenchong Li ◽

Zuguang Ma ◽

Zixuan Zhou ◽

Hongkai Zhuang ◽

...

Keyword(s):

Pancreatic Cancer ◽

Risk Model ◽

Area Under The Curve ◽

Metabolic Reprogramming ◽

Bioinformatics Analyses ◽

Mutation Status ◽

Metabolic Characteristics ◽

Model Based ◽

Metabolic Genes ◽

Prognostic Prediction

Background. KRAS was reported to affect some metabolic genes and promote metabolic reprogramming in solid tumors. However, there was no comprehensive analysis to explore KRAS-associated metabolic signature or risk model for pancreatic cancer (PC). Methods. In the current study, multiple bioinformatics analyses were used to identify differentially expressed metabolic genes based on KRAS mutation status in PC. Then, we developed and validated a prognostic risk model based on the selected KRAS-associated metabolic genes. Besides, we explored the association between the risk model and the metabolic characteristics as well as gemcitabine-associated chemoresistance in PC. Results. 6 KRAS-associated metabolic genes (i.e., CYP2S1, GPX3, FTCD, ENPP2, UGT1A10, and XDH) were selected and enrolled to establish a prognostic risk model. The prognostic model had a high C-index of 0.733 for overall survival (OS) in TCGA pancreatic cancer database. The area under the curve (AUC) values of 1- and 3-year survival were both greater than 0.70. Then, the risk model was validated in two GEO datasets and also presented a satisfactory discrimination and calibration performance. Further, we found that the expression of some KRAS-driven glycolysis-associated genes (PKM, GLUT1, HK2, and LDHA) and gemcitabine-associated chemoresistance genes (i.e., CDA and RMM2) was significantly upregulated in high-risk PC patients evaluated by the risk model. Conclusions. We constructed a risk model based on 6 KRAS-associated metabolic genes, which predicted patients’ survival with high accuracy and reflected tumor metabolic characteristics and gemcitabine-associated chemoresistance in PC.

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Effects of Metformin on Reproductive, Endocrine, and Metabolic Characteristics of Female Offspring in a Rat Model of Letrozole-induced Polycystic Ovarian Syndrome With Insulin Resistant

10.21203/rs.3.rs-122468/v1 ◽

2020 ◽

Author(s):

Yidong Xie ◽

Li Xiao ◽

Xiaohan Shi ◽

Yifan Zhao ◽

Xiaohong Li ◽

...

Keyword(s):

Insulin Resistance ◽

Polycystic Ovary Syndrome ◽

Rat Model ◽

Wistar Rats ◽

Polycystic Ovary ◽

Female Offspring ◽

Ovary Syndrome ◽

Metabolic Characteristics ◽

Reproductive Endocrine ◽

The Impact

Abstract Background: Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disorder that has many characteristic features including hyperandrogenemia, insulin resistance and obesity. The beneficial effects of metformin on reproduction, metabolism and endocrine, especially with the capacity to ameliorate insulin resistance (IR) in polycystic ovary syndrome (PCOS), place it as a good alternative for its widely prescribed, but its association with PCOS offspring remains uncertain. We aim to investigate the impact of metformin on reproductive, endocrine and metabolic characteristics in female offspring born to letrozole-induced PCOS-IR rats.Methods: 45 female wistar rats were implanted with letrozole-continuous-release pellets or placebo, subsequently treated with metformin or vehicle control, then mated with healthy male wistar rats. Estrous cycle, endocrine hormone profile, fasting insulin measurements and glucose tolerance test have been investigated and the expression of INSR in pancreas, FSHR and LHCGR in ovaries have been analyzed with Quantitative Real-time Polymerase Chain Reaction and Western Blotting assay.Results: Decreased conception rate and increased multiple pregnancy rates were found in PCOS-IR rats, which significantly improved after metformin treatment. Metformin significantly decreased the risk of body weight gain and increased INSR expression of pancreas in female F1 offspring in PCOS-IR rats. Decreased FSHR and increased LHCGR expressions in ovary were observed in female F1 rats of PCOS-IR and PCOS-IR+Met group. Nevertheless, there were no significant differences of INSR, FSHR and LHCGR expressions in female F2 offspring of PCOS-IR rats, as well as other PCOS phenotypes.Conclusions: The current study indicates that widespread reproductive, endocrine and metabolic changes in letrozole induced PCOS-IR rat model, but those PCOS phenotypes could not be inherit to offspring generations stably. Metformin may contribute to improve obesity, hyperinsulinemia and insulin resistance of female F1 offspring in PCOS-IR. The results of this study can be used as a theoretical basis for supporting metformin-using in the treatment of PCOS-IR patients.

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