scholarly journals Ameliorative Effects of Bredemolic Acid on Markers Associated with Renal Dysfunction in a Diet-Induced Prediabetic Rat Model

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Akinjide Moses Akinnuga ◽  
Angezwa Siboto ◽  
Bongiwe Khumalo ◽  
Ntethelelo Hopewell Sibiya ◽  
Phikelelani Ngubane ◽  
...  

Recently, studies have shown that renal dysfunction is associated not only with overt diabetes but also with the preceding stage known as prediabetes. Diet and pharmacological interventions are the therapeutic approaches to managing prediabetes, but the compliance in combining the two interventions is low. Hence, the efficacy of pharmacological intervention is reduced without diet modification. In our previous study, we established that bredemolic acid (BA) ameliorated glucose homeostasis via increased GLUT 4 expression in the skeletal muscle of prediabetic rats in the absence of diet intervention. However, the effects of bredemolic acid on renal function in prediabetic condition are unknown. Therefore, this study was aimed at investigating the ameliorative effects of bredemolic acid on renal dysfunction in a diet-induced prediabetic rat model. Thirty-six Sprague-Dawley male rats (150–180 g) were divided into two groups: the nonprediabetic (n=6) and prediabetic (n=30) groups which were fed normal diet (ND) and high-fat high-carbohydrate (HFHC) diet, respectively, for 20 weeks. After the 20th week, the prediabetic groups were subdivided into prediabetic control (PD) and 4 other prediabetic groups which were treated with either BA (80 mg/kg) or metformin (MET, 500 mg/kg) for further 12 weeks (21st to 32nd). Plasma, urine, and kidney samples were collected for biochemical analysis. The untreated prediabetic (PD) rats presented increased fluid intake and urine output; increased creatinine, urea, and uric acid plasma concentrations; albuminuria; proteinuria; sodium retention; potassium loss; increased aldosterone and kidney injury molecule (KIM-1) concentration; and increased urinary podocin mRNA expression. However, BA administration attenuated the renal markers and oxidative stress and decreased the urinary podocin mRNA expression. In conclusion, BA administration, regardless of diet modification, attenuates renal dysfunction in an experimentally induced prediabetic state.

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Baojian Xue ◽  
Terry Beltz ◽  
Fang Guo ◽  
David M Pollock ◽  
Jennifer S Pollock ◽  
...  

Separation of neonatal rodent pups from their mothers has been used as a model to study the effects of early life stress (ELS) on behavioral and physiological responses in adults. Using an Induction-Delay-Expression experimental paradigm, our previous studies demonstrate that a wide range of stressors administered during an induction period produces hypertensive response sensitization (HTRS) in response to a subsequent pro-hypertensive stimulus. HTRS is accompanied by activation of the brain renin-angiotensin system (RAS) and CNS inflammation. The present study investigated whether ELS induces HTRS and changes in brain-related underlying mechanisms. Rat neonates from Sprague-Dawley breeders were subjected to ELS by separating them each morning from their mothers for 3 h on postnatal days 2 to 14. Pups from non-handled litters formed control groups. At 10 weeks of age, male rats were used to evaluate blood pressure and autonomic function using telemetric probes and pharmacological methods. In addition, in separate control and ELS groups, the lamina terminalis (LT) structures and the hypothalamic paraventricular nucleus (PVN) were analyzed for mRNA expression of RAS components and proinflammatory cytokines. Adult ELS rats as compared to non-separated controls exhibited 1) HTRS during expression testing using 2 week ANG II infusions (120 ng/kg/min s.c.; ELS animals, Δ45.5±4.5 mmHg vs. controls, Δ22.4±3.1 mmHg); 2) a greater reduction in mean arterial pressure following ganglionic blockade (hexamethonium, 30 mg/kg, ip), 3) increased sympathetic drive to the heart (atenolol, 8 mg/kg, ip), 4) decreased vagal tone (atropine, 8 mg/kg, ip), and 5) increased mRNA expression of several components of the brain RAS and proinflammatory cytokines in the LT and PVN. These results suggest that maternal ELS may predispose individuals to hypertension that is mediated by upregulation of the brain RAS and proinflammatory cytokines and increased sympathetic drive to the cardiovascular system.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H R Helmi ◽  
A P Sunjaya ◽  
D Limanan ◽  
A R Prijanti ◽  
S W A Jusman ◽  
...  

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


2015 ◽  
Vol 35 (5) ◽  
pp. 506-516 ◽  
Author(s):  
Keiichi Wakabayashi ◽  
Chieko Hamada ◽  
Reo Kanda ◽  
Takanori Nakano ◽  
Hiroaki Io ◽  
...  

BackgroundPreventing peritoneal damage during peritoneal dialysis is critical. Reactive oxygen species (ROS) have an important role in peritoneal damage; however, few studies have investigated this. We aimed to determine the effects of oral astaxanthin (AST) supplementation in a peritoneal fibrosis (PF) rat model.MethodsThirty-seven Sprague-Dawley rats were divided into 5 groups: Control 1 (fed a normal diet without stimulation), Control 2 (fed an AST-supplemented diet without stimulation), Group 1 (fed a normal diet with 8% chlorhexidine gluconate [CG] stimulation for 3 weeks), Group 2 (fed a 0.06% AST-supplemented diet with CG stimulation), and Group 3 (fed a 0.06% AST-supplemented diet that was initiated 4 weeks before CG stimulation). Peritoneal fibrosis, vascular proliferation, and fibrosis-related factor expression were examined.ResultsPeritoneal thickness was significantly suppressed by AST supplementation. Astaxanthin diminished the number of CD68-, 8-hydroxy-2'–deoxyguanosine (8-OHdG)-, and monocyte chemoattractant protein-1 (MCP-1)-positive cells. Type 3 collagen, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and MCP-1 mRNA expression was significantly lower in Group 3 than in Group 1. Increased transforming growth factor-β (TGF-β) and Snail mRNA expression, vascular density, and the number of α–smooth muscle actin (α–SMA)-positive cells were also decreased in Group 3.ConclusionAstaxanthin suppressed PF development through the inhibition of inflammation and oxidation in PF rats. It appears that the anti-oxidative agent AST may be useful for the prevention of peritoneal damage.


Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1260 ◽  
Author(s):  
Marta Anna Szychlinska ◽  
Rosa Imbesi ◽  
Paola Castrogiovanni ◽  
Claudia Guglielmino ◽  
Silvia Ravalli ◽  
...  

Deficiency in vitamin D (Vit D) has been widely associated with several musculoskeletal diseases. However, the effects of the exogenous Vit D supplementation are still unclear in the prevention of the latter, especially in the cartilage developmental period. The aim of this study was to compare the effects of Vit D supplementation and restriction on the articular cartilage development in healthy young sedentary rats. To this aim, twelve nine-week-old healthy Sprague–Dawley male rats were subjected to Vit D-based experimental diets: R, with a content in Vit D of 1400 IU/kg; R-DS, with a Vit D supplementation (4000 IU/kg); R-DR, with a Vit D restriction (0 IU/kg) for 10 weeks. The morphology, thickness and expression of cartilage-associated molecules such as collagen type II/X, lubricin and Vit D receptor (VDR), were assessed. Histological, histomorphometric and immunohistochemical evaluations were made on rat tibial cartilage samples. In the present experimental model, restriction of Vit D intake induced: The lower thickness of cartilage compared both to R (p = < 0.0001) and R-DS (p = < 0.0001); reduction of proteoglycans in the extracellular matrix (ECM) compared both to R (p = 0.0359) and R-DS (p = < 0.0001); decreased collagen II (Col II) with respect both to R (p = 0.0076) and R-DS (p = 0.0016); increased collagen X (Col X) immunoexpression when compared both to R (p = < 0.0001) and R-DS (p = < 0.0001), confirming data from the literature. Instead, supplementation of Vit D intake induced: Higher cartilage thickness with respect both to R (p = 0.0071) and R-DR (p = < 0.0001); increase of ECM proteoglycan deposition compared both to R (p = 0.0175) and R-DR (p = < 0.0001); higher immunoexpression of lubricin with respect both to R (p = 0.001) and R-DR (p = 0.0008). These results suggest that Vit D supplementation with diet, already after 10 weeks, has a favorable impact on the articular cartilage thickness development, joint lubrication and ECM fibers deposition in a young healthy rat model.


2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S429-S429
Author(s):  
Jiajun Liu ◽  
Sean Avedissian ◽  
Gwendolyn Pais ◽  
Medha Joshi ◽  
Nathaniel J Rhodes ◽  
...  

Abstract Background For treatment of central nervous system infections caused by GNB, adequate cefepime concentrations are required in the cerebral spinal fluid (CSF) and brain. However, high plasma cefepime exposures have resulted in neurotoxicity. There is a need to understand the real-time pharmacokinetic (PK) relationship between plasma and CSF concentrations as serial CSF sampling is not regularly performed. Methods Male Sprague-Dawley rats received cefepime via an internal jugular vein catheter. A total daily dose of 150 mg/kg/day was administered as a single injection every 24 hours for 4 days. Plasma samples (mean n = 5 per rat) was obtained via a second dedicated catheter, with up to five samples obtained on a single concentration–time curve. CSF sampling occurred via an intracisternal catheter, with up to two samples taken every 24 hours. Cefepime in plasma and CSF were quantified via LC–MS/MS. PK analyses were conducted using Pmetrics for R. Multiple physiologic compartmental models were fit, with the ultimate model selected by Akaike score and rule of parsimony. Each rat’s concentrations were predicted from the final model, and predictive performance was evaluated with bias and imprecision of the population and Bayesian posterior prediction models. PK parameters were estimated, and PK exposures during the first 24 hours (i.e., AUC0–24, CMAX0–24, CMIN0–24) were calculated for each rat from Bayesian posteriors. Results Eleven rats contributed PK data. A three-compartment model fit the data well [Figure 1: Plasma, Population (a) and Bayesian (b); Figure 2: CSF, Population (a) and Bayesian (b)]. Population median parameter values (CV%) for rate constant (Ke), volume central compartment (V1), volume CSF compartment (V3), rate to/from central/peripheral compartment (KCP, KPC), rate to/from central/CSF compartment (K13, K31) were: 5.04 hour−1 (43.4%), 0.069 L (39.24%), 0.28 hour−1 (52.11%), 17.42 hour−1(34.83%), 0.32 hour−1 (165.3), 0.31 hour−1 (79.89), respectively. Noncompartmental analysis of the Bayesian posteriors revealed a plasma median half-life, AUC0–24, CMAX0–24, and CMIN0–24 of 2.6 hours, 158.1 mg hour/L, 189.3 mg/L, and 0.0003 mg/L from the first dose. Conclusion Cefepime transit to the CSF is rapid and highly predictable in the rat model. This model will be highly useful for understanding neurotoxicity outcomes for cefepime. Disclosures J. Liu, Merck: Grant fund from Merck, Research grant.


2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Hye-Kyung Choi ◽  
Eun-Kyung Won ◽  
Young Pyo Jang ◽  
Se-Young Choung

The antiobesity effects ofCodonopsis lanceolata(CL) were evaluated in a high-calorie/high-fat-diet (HFD-) induced obesity rat model and 3T3-L1 cells. The Sprague-Dawley male rats were fed a normal diet (ND) or a HFD for a period of 12 weeks. The rats were subdivided into groups: ND, ND + wildCodonopsis lanceolata(wCL) (900 mg/kg/day, p.o.), ND + cultivatedCodonopsis lanceolata(cCL) (900 mg/kg/day, p.o.), HFD, HFD + wCL (100, 300, or 900 mg/kg/day, p.o.), HFD + cCL (100, 300, or 900 mg/kg/day, p.o.), and HFD + sibutramine. The body weight gains of the administered HFD + CL (wCL or CCL) were lower than those of the rats fed with only the HFD group. Moreover, the weight of adipose pads and the serum levels of triglycerides, total cholesterol, and low density lipoprotein cholesterol in the group administered HDL + CL were significantly lower than in the HFD group. The inhibitory effect of lipid accumulation in 3T3-L1 cells was measured by Oil Red O staining and reverse transcription-polymerase chain reaction (RT-PCR). Treatment of 3T3-L1 cells with wCL inhibited lipid accumulation and expression of C/EBPαand PPARγ. These results suggest that CL has a great potential as a functional food with anti-obesity effects and as a therapeutic alternative in the treatment of obesity.


2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Marzia Ferretti ◽  
Francesco Cavani ◽  
Alberto Smargiassi ◽  
Laura Roli ◽  
Carla Palumbo

Rats fed calcium-deprived diet develop osteoporosis due to enhanced bone resorption, secondary to parathyroid overactivity resulting from nutritional hypocalcemia. Therefore, rats provide a good experimental animal model for studying bone modelling alterations during biochemical osteoporosis. Three-month-old Sprague-Dawley male rats were divided into 4 groups: (1) baseline, (2) normal diet for 4 weeks, (3) calcium-deprived diet for 4 weeks, and (4) calcium-deprived diet for 4 weeks and concomitant administration of PTH (1-34) 40 µg/Kg/day. Histomorphometrical analyses were made on cortical and trabecular bone of lumbar vertebral body as well as of mid-diaphysis and distal metaphysis of femur. In all rats fed calcium-deprived diet, despite the reduction of trabecular number (due to the maintenance of mineral homeostasis), an intense activity of bone deposition occurs on the surface of the few remaining trabeculae (in answering to mechanical stresses and, consequently, to maintain the skeletal homeostasis). Different responses were detected in different sites of cortical bone, depending on their main function in answering mineral or skeletal homeostasis. This study represents the starting point for work-in-progress researches, with the aim of defining in detail timing and manners of evolution and recovery of biochemical osteoporosis.


2021 ◽  
Vol 65 (2) ◽  
pp. 193-200
Author(s):  
Nilay Seyidoğlu ◽  
Eda Köşeli ◽  
Rovshan Gurbanlı ◽  
Cenk Aydın

Abstract Introduction There is a balance between oxidative stress, antioxidant capacity and immune response. Their roles in physiological and behavioural mechanisms are important for the maintenance of the organism’s internal equilibrium. This study aimed to evaluate the antioxidant effects of the exogenous alga Spirulina platensis (Arthrospira platensis) in a stress-induced rat model, and to describe its possible mechanism of action. Material and Methods Thirty-six adult male Sprague Dawley rats were separated into four groups: control (C), stress (S), S. platensis (Sp), and S. platensis + stress (SpS). The rats in groups Sp and SpS were fed with 1,500 mg/kg b.w./day Spirulina platensis for 28 days. All rats were exposed to prolonged light phase conditions (18 h light : 6 h dark) for 14 days. The SpS and S groups were exposed to stress by being kept isolated and in a crowded environment. Blood samples were obtained by puncturing the heart on the 28th day. The effect of stress on serum corticosterone, oxidative stress markers (TOS, TAC, PON1, OSI) and immunological parameters (IL-2, IL-4, IFN-ɣ) were tested. Also, the brain, heart, intestines (duodenum, ileum, and colon), kidney, liver, spleen, and stomach of the rats were weighed. Results Serum corticosterone levels were higher in the S group than in the C group, and significantly lower in the SpS group than in the S group. Mean total antioxidant capacity were lower in the S group than in the C group, and Spirulina reversed this change. Although not significantly different, IL-2 was lower in the S group than in the C group. However, in the SpS group, IL-2 increased due to Spirulina platensis mitigating effects of stress. Conclusion Male rats fed a diet with Spirulina platensis could experience significantly milder physiological changes during stress, although stress patterns may be different. Exogenous antioxidant supplements merit further investigation in animals and humans where the endogenous defence mechanism against stress may not be sufficient.


2018 ◽  
Vol 52 (2) ◽  
pp. 69-75 ◽  
Author(s):  
Titin Andri Wihastuti ◽  
Teuku Heriansyah ◽  
Hanifa Hanifa ◽  
Sri Andarini ◽  
Zuhrotus Sholichah ◽  
...  

AbstractObjective. Increase in the low-density lipoprotein (LDL) level in diabetes mellitus and atherosclerosis is related to lipoprotein associated phospholipase A2 (Lp-PLA2). Lp-PLA2 is an enzyme that produces lysophosphatidylcholine (LysoPC) and oxidized nonesterified fatty acids (oxNEFA). LysoPC regulates inflammation mediators, including intra-cellular adhesion molecule-1 (ICAM-1). Darapladib is known as a Lp-PLA2 specific inhibitor. The aim of this study was to reveal the effect of darapladib on the foam cell number, inducible nitric oxide synthase (iNOS), and ICAM-1 expression in aorta at early stages of the atherosclerosis in type 2 diabetes mellitus Sprague-Dawley rat model.Methods. Thirty Sprague-Dawley male rats were divided into 3 main groups: control, rats with type 2 diabetes mellitus (T2DM), and T2DM rats treated with darapladib (T2DM-DP). Each group was divided into 2 subgroups according the time of treatment: 8-week and 16-week treatment group. Fasting blood glucose, insulin resistance, and lipid profile were measured and analyzed to ensure T2DM model. The foam cells number were detected using hematoxylin-eosin (HE) staining and the expression of iNOS and ICAM-1 was analyzed using double immunofluorescence staining.Results. Induction of T2DM in male Sprague-Dawley rats after high fat diet and streptozotocin injection was confirmed by elevated levels of total cholesterol and LDL and increased fasting glucose and insulin levels compared to controls after both times of treatment. Moreover, T2DM in rats induced a significant increase (p<0.05) in the foam cells number and iNOS and ICAM-1 expression in aorta compared to controls after both treatment times. Darapladib treatment significantly reduced (p<0.05) foam cells number as well as iNOS expression in aorta in rats with T2DM after both treatment times. A significant decrease (p<0.05) in ICAM-1 expression in aorta was observed after darapladib treatment in rats with T2DM only after 8 weeks of treatment.Conclusion. Our data indicate that darapladib can decrease the foam cells number, iNOS, and ICAM-1 expression in aorta at the early stages of atherosclerosis in T2DM rat model.


2019 ◽  
Vol 44 (2) ◽  
pp. 105-118
Author(s):  
Zubeyde Ercan ◽  
Gulnihal Deniz ◽  
Fatma Caf ◽  
Sermin Algul ◽  
Abdullah Gazioglu ◽  
...  

The action mechanism of acupuncture, one of the alternative methods used in obesity treatment, is unknown. The purpose of this study was to investigate the effect of electro acupuncture on weight loss and whether acupuncture treatment can change circulating levels of irisin, nesfatin-l and preptin, which have been discovered in recent years and plays an important role in nutrition and energy metabolism. Irisin, a newly discovered myokine, is associated with increased energy consumption and has a potential role in obesity. Preptin, present in islet b-cells of pancreas and associated with the carbohydrate metabolism, nesfatin1 is an anorexogenic peptide composed of 82 amino acids and regulates food intake by modulating neuropeptides in feeding centers in the brain. These three new hormones regulate energy intake and expenditure and preserve energy homeostasis and composition. In this study 4 weeks old Sprague Dawley male rats (n=16) were randomly divided into 2 groups which were the control (C): normal diet and obese (0): high fat diet (HFD) groups. 105 After 16 weeks which obesity was developed, electroacupuncture (EA) was performed to rats once in every second days for 3 times weekly for four consecutive weeks. EA was applied bilaterally to Zusanli (ST36), Bai Hui (Du20), He Gu (Li4), Tianshu (ST25) and Sanyinjiao (SP6) acupoints in animals to both groups. Blood was collected before and after EA and serum irisin, nesfatin-l and preptin levels were analyzed by ELISA (Enzyme-InducedImmunosorbent Analysis) method. After four week EA treatment, there was sginificant decrease of the average body weight in both groups rats. There were increases in the serum nesfatin-l and preptin levels in the both groups after acupuncture. A decrease was observed in the irisin levels in obese group, but an increase in the control group. These findings suggest that electroacupuncture may help to weight loss due to its effects on some important metabolic hormones such as irisin, nesfatin-l and preptin only for a few weeks. It is thought that the changes of these hormones levels may playa role in beneficial effect of acupuncture used in the treatment of human obesity. The application of EA in the treatment of obesity is very effective, which may have led to weight loss by altering these hormone levels in obese people.


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