Lactose maldigestion during methotrexate-induced gastrointestinal mucositis in a rat model

2011 ◽  
Vol 300 (2) ◽  
pp. G283-G291 ◽  
Author(s):  
M. Fijlstra ◽  
E. H. H. M. Rings ◽  
H. J. Verkade ◽  
T. H. van Dijk ◽  
W. A. Kamps ◽  
...  

Patients with chemotherapy-induced gastrointestinal mucositis suffer from anorexia, diarrhea, and stomach pain, often causing weight loss and malnutrition. When the intestinal function during mucositis would be known, a rational feeding strategy might improve the nutritional state, accelerate recuperation, and increase survival of mucositis patients. We developed a methotrexate (MTX)-induced mucositis rat model to study nutrient digestion and absorption. To determine lactose digestion and absorption of its derivative glucose during mucositis, we injected Wistar rats intravenously with MTX (60 mg/kg) or 0.9% NaCl (controls). Four days later, we orally administered trace amounts of [1-13C]lactose and [U-13C]glucose and quantified the appearance of labeled glucose in the blood for 3 h. Finally, we determined plasma citrulline level and harvested the small intestine to assess histology, myeloperoxidase level, glycohydrolase activity, immunohistochemical protein, and mRNA expression. MTX-treated rats showed profound villus atrophy and epithelial damage. During the experimental period, the absorption of lactose-derived [1-13C]glucose was 4.2-fold decreased in MTX-treated rats compared with controls ( P < 0.01). Lactose-derived [1-13C]glucose absorption correlated strongly with villus length (rho = 0.86, P < 0.001) and with plasma citrulline level (rho = 0.81, P < 0.001). MTX treatment decreased jejunal lactase activity (19.5-fold, P < 0.01) and immunohistochemical protein and mRNA expression (39.7-fold, P < 0.01) compared with controls. Interestingly, MTX treatment did not affect the absorption of [U-13C]glucose during the experimental period. We conclude that lactose digestion is severely decreased during mucositis while glucose absorption is still intact, when supplied in trace amounts. Plasma citrulline level might be a useful objective, noninvasive marker for lactose maldigestion during mucositis in clinic.

2017 ◽  
Vol 6 (8) ◽  
pp. 5446
Author(s):  
Reddy I.J. ◽  
Ashish Mishra ◽  
Mondal S.

The objective of this study was to establish the effects of red spectrum of light (650nm, treated n=12) and normal spectrum of light (450nm control=12) on GnRH-I and GnIH mRNA expression, amplitude and frequency of luteinizing hormone (LH) and egg production from 42 to 52 weeks of age in white leghorn hens. Blood samples were collected at weekly interval from both the groups. At the 47th week of age blood samples from both the groups were collected at every 3 h for 36h to study the pulsatile secretion of LH surges. GnRH and GnIH mRNA expression pattern was studied between control and treated birds. Egg production and pause days were calculated between the two groups. LH concentration in the plasma was increased significantly (P<0.01) in hens exposed to red spectrum of light. Plasma LH concentration was higher (P<0.01) in treated birds with more number of LH surges. The amplitude and frequencies of LH were advanced in birds exposed to red spectrum of light during 36 h of sampling at 3h intervals. GnRH-I mRNA concentration was significantly (P<0.01) higher, whereas GnIH mRNA was significantly (P<0.01) lower in birds exposed to red spectrum of light compared to controls. It is hypothesized that exposure of birds to red spectrum of light enhanced (P<0.01) GnRH-I mRNA, along with LH required for ovulation and egg lay. During 77 days (42-52 weeks of age) of the experimental period, egg production was increased (p<0.01) with lower incidence of pause days in the treated group. It is concluded that low GnIH mRNA and higher levels of GnRH-I mRNA, LH, lower number of pause days enabled the birds to lay more eggs by stimulating GnRH through red spectrum of light.


Animals ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 753
Author(s):  
Andre Barany ◽  
Juan Fuentes ◽  
Gonzalo Martínez-Rodríguez ◽  
Juan Miguel Mancera

Several studies in fish have shown that aflatoxin B1 (AFB1) causes a disparity of species-dependent physiological disorders without compromising survival. We studied the effect of dietary administration of AFB1 (2 mg AFB1 kg−1 diet) in gilthead seabream (Sparus aurata) juveniles in combination with a challenge by stocking density (4 vs. 40 g L−1). The experimental period duration was ten days, and the diet with AFB1 was administered to the fish for 85 days prior to the stocking density challenge. Our results indicated an alteration in the carbohydrate and lipid metabolites mobilization in the AFB1 fed group, which was intensified at high stocking density (HSD). The CT group at HSD increased plasma cortisol levels, as expected, whereas the AFB1-HSD group did not. The star mRNA expression, an enzyme involved in cortisol synthesis in the head kidney, presented a ninefold increase in the AFB1 group at low stocking density (LSD) compared to the CT-LSD group. Adenohypophyseal gh mRNA expression increased in the AFB1-HSD but not in the CT-HSD group. Overall, these results confirmed that chronic AFB1 dietary exposure alters the adequate endocrinological physiological cascade response in S. aurata, compromising the expected stress response to an additional stressor, such as overcrowding.


2002 ◽  
Vol 282 (1) ◽  
pp. G156-G164 ◽  
Author(s):  
Bohuslav Dvorak ◽  
Melissa D. Halpern ◽  
Hana Holubec ◽  
Catherine S. Williams ◽  
Debra L. McWilliam ◽  
...  

Necrotizing enterocolitis (NEC) is the most common gastrointestinal disease of prematurely born infants. Maternal milk plays an important protective role against NEC development and is the major source of epidermal growth factor (EGF) for neonates. The aim of this study was to examine the effect of orally administered EGF on the incidence of NEC in a neonatal rat model. Newborn rats were artificially fed either with growth factor-free rat milk substitute (RMS) or RMS supplemented with 500 ng/ml of EGF (RMS+EGF). Experimental NEC was induced by exposure to asphyxia and cold stress. Development of NEC was evaluated by gross and histological scoring of damage in the ileum. Ileal EGF receptor (EGF-R), EGF, and transforming growth factor-α mRNA expression was assessed by RT competitive-PCR, and the EGF-R was localized by immunohistochemistry. EGF supplementation of formula reduced the incidence and severity of NEC in rats (13/16 RMS vs. 4/13 RMS+EGF). Ileal EGF-R mRNA expression was markedly increased in the RMS group compared with RMS+EGF. Enhanced EGF-R expression in the RMS group was localized predominantly in the epithelial cells of injured ileum. These data suggest a new potential therapeutic approach for the prevention and treatment of NEC.


2015 ◽  
pp. 153-159 ◽  
Author(s):  
M. M. GOVENDER ◽  
A. NADAR

Oxidative stress is an imbalance between free radicals and antioxidants, and is an important etiological factor in the development of hypertension. Recent experimental evidence suggests that subpressor doses of angiotensin II elevate oxidative stress and blood pressure. We aimed to investigate the oxidative stress related mechanism by which a subpressor dose of angiotensin II induces hypertension in a normotensive rat model. Normotensive male Wistar rats were infused with a subpressor dose of angiotensin II for 28 days. The control group was sham operated and infused with saline only. Plasma angiotensin II and H2O2 levels, whole-blood glutathione peroxidase, and AT-1a, Cu/Zn SOD, and p22phox mRNA expression in the aorta was assessed. Systolic and diastolic blood pressures were elevated in the experimental group. There was no change in angiotensin II levels, but a significant increase in AT-1a mRNA expression was found in the experimental group. mRNA expression of p22phox was increased significantly and Cu/Zn SOD decreased significantly in the experimental group. There was no significant change to the H2O2 and GPx levels. Angiotensin II manipulates the free radical-antioxidant balance in the vasculature by selectively increasing O2− production and decreasing SOD activity and causes an oxidative stress induced elevation in blood pressure in the Wistar rat.


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


Critical Care ◽  
2019 ◽  
Vol 23 (1) ◽  
Author(s):  
Patrick M. Honore ◽  
David De Bels ◽  
Andrea Gallerani ◽  
Rachid Attou ◽  
Willem Boer

2020 ◽  
Vol 227 ◽  
pp. 151419
Author(s):  
Elisa J. Campos ◽  
João Martins ◽  
Dan Brudzewsky ◽  
David P.D. Woldbye ◽  
António F. Ambrósio

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Jun Zhao ◽  
Huiling Tian ◽  
Hongtao Song ◽  
Xu Wang ◽  
Tong Luo ◽  
...  

The current study aimed to investigate the effects and mechanisms of electroacupuncture (EA) treatment applied to Bai hui (GV20) and Yin tang (GV29) acupoints (1 mA, 2 Hz, continuous wave, 20 minutes) for 28 days in a rat model of chronic unpredictable mild stress (CUMS) on reuptake of serotonin (5-hydroxytryptamine (5-HT)) and miRNA-16 levels in the hippocampus and serum. Rats were housed in individual cages, and CUMS was used to establish a rat model of depression. After EA treatment for 4 weeks, behavioral changes and indices including 5-HT transporter (SERT), 5-HT, and miRNA-16 levels in the hippocampus and serum were examined. The EA treatment significantly improved base levels of sucrose preference and exploratory behavior and significantly decreased SERT protein and mRNA expression in the hippocampus of depressed rats. Significantly increased 5-HT levels were observed, and miRNA-16 levels were significantly decreased in the hippocampus and serum of depressed rats. In conclusion, the antidepressant effects of EA treatment may be affected via inhibition of 5-HT reuptake, upregulation of 5-HT levels, and inhibition of miRNA-16 expression in the hippocampus and serum.


2020 ◽  
Vol 98 (2) ◽  
Author(s):  
Lanmei Yin ◽  
Jun Li ◽  
Huiru Wang ◽  
Zhenfeng Yi ◽  
Lei Wang ◽  
...  

Abstract Vitamin B6 (VB6), which is an essential functional substance for biosome, plays an irreplaceable role in animal health. However, there are few studies that focus on the correlation between VB6 and intestinal health in weaned piglets. This study was conducted to investigate the effects of VB6 on the growth performance, intestinal morphology, and inflammatory cytokines and amino acid (AA) transporters mRNA expression in weaned piglets that are fed a low crude-protein (CP, 18%) diet. Eighteen crossbred piglets with initial body weights of 7.03 ± 0.17 kg (means ± SEM), weaned at 21-d age, were randomly assigned three diets with 0, 4, and 7 mg/kg VB6 supplementation, respectively. The experimental period lasted 14 days. Our results showed that there were no significant differences in growth performance, diarrhea rate, and biochemical parameters among the three treatments. In the jejunum, dietary VB6 supplementation did not affect the morphology and positive Ki67 counts. Dietary supplementation with 4 mg/kg VB6 decreased the mRNA expression of COX-2, IL-10, and TGF-β (P &lt; 0.05). Dietary supplementation with 7 mg/kg VB6 increased the mRNA expression of SLC7A1, SLC7A6, SLC16A14, and SLC38A5 (P &lt; 0.05) and 4 or 7 mg/kg VB6 decreased SLC36A1 mRNA expression (P &lt; 0.05). In the ileum, VB6 supplementation did not affect positive Ki67 counts but significantly decreased villus area (P &lt; 0.05) and tended to decrease villus height (P = 0.093). Dietary supplementation with 4 mg/kg VB6 had significantly increased the mRNA expression of IL-1β, TNF-α, COX-2, IL-10, and TGF-β (P &lt; 0.05). Dietary supplementation with 4 or 7 mg/kg VB6 had significantly decreased SLC6A20, SLC7A1, SLC7A6, SLC16A14, and SLC38A5 mRNA expression (P &lt; 0.05). These findings suggest that dietary supplementation of VB6 mainly down-regulated inflammatory cytokines and up-regulated AA transporters mRNA expression in jejunum, while up-regulated (4 mg/kg) inflammatory cytokines and down-regulated AA transporters mRNA expression in ileum, which may provide a reference for the intestinal development of weaned piglets that are fed a low-CP diet.


2008 ◽  
Vol 36 (3-4) ◽  
pp. 170-176 ◽  
Author(s):  
Toshihiro Fujiwara ◽  
Tateki Kubo ◽  
Yoshihisa Koyama ◽  
Koichi Tomita ◽  
Kenji Yano ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document