scholarly journals ACTION OF HYDROGEN SULFIDE DONORS ON NITROSO-OXIDATIVE PROCESSES IN SMALL INTESTINE OF RATS WITH METHOTREXATE-INDUCED ENTEROPATHY

Author(s):  
Yu. O. Sklyarova ◽  
I. S. Fomenko

Introduction. Medication-induced enteropathy plays an important part among factors leading to the development of small intestinal injury. There are some evidences indicating a potential preventive action of hydrogen sulfide (H2S) donors against drug-induced enteropathies based on that fact that the use of the most of enterotoxic medications including anti-tumor drugs leads to the suppression of this gaseous mediator production. The aim of the study – to compare the action of H2S donors in small intestine of rats on parameters of NO-synthase system and oxidative stress under condition of methotrexate-induced enteropathy. Research Methods. The experimental procedures were carried out on rats which on the background of methotrexate-induced enteropathy received H2S donors NaHS (1 and 10 mg/kg) and L-cysteine. Following biochemical parameters were measured in small intestinal mucosa: activity of NO-synthases, myeloperoxidase, superoxide dismutase and catalase; concentrations of NOx (nitrite/nitrate) and malonic dialdehyde. H2S concentration was determined in blood serum. Results and Discussion. Administration of methotrexate didn’t cause any visible changes of small intestine surface, however led to serious biochemical changes. NO concentration increased as a result of iNOS activation (more than fivefold (p≤0.01). Simultaneously concentration of H2S decreased in blood serum. Administration of H2.S donors practically returned these parameters to their normal value. Methotrexate-induced enteropathy caused the increase of myeloperoxidase activity by 66 %, p≤0.01, indicating of inflammatory process formation and activation of lipid peroxidation. Administration of NaHS didn’t cause any serious changes in myeloperoxidase activity, however increased SOD activity and practically retuned it to its norm. Conclusions. Nirtoso-oxidative stress plays the key role in enteropathy formation resulted in methotrexate administration. H2S donors modulate parameters of NO-synthase system and activity of SOD.

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Zhongshen Kuang ◽  
Tingting Jin ◽  
ChangYi Wu ◽  
Yanan Zong ◽  
Panpan Yin ◽  
...  

This study is aimed at exploring the effects of lentinan on small intestinal mucosa as well as lung and liver injury in mice with gut-origin sepsis. Cecal ligation and perforation (CLP) were used to construct a mouse model of gut-origin sepsis. The mice were randomly divided into six groups: sham operation group (sham), gut-origin sepsis model group (CLP), ulinastatin-positive drug control group (UTI), lentinan low concentration group (LTN-L, 5 mg/kg), lentinan medium concentration group (LTN-M, 10 mg/kg), and lentinan high concentration group (LTN-H, 20 mg/kg). H&E staining was used to detect the pathological damage of the small intestine, liver, and lung. The serum of mice in each group was collected to detect the expression changes of inflammatory cytokines, oxidative stress biomarkers, and liver function indexes. In vitro assessment of bacterial translocation was achieved through inoculated culture media. Western blot and RT-qPCR were used to detect the expression of molecules related to the NF-κB signaling pathway in the small intestine tissues of mice. The results showed that compared with the CLP group, the injury degree of the small intestine, liver, and lung in mice with gut-origin sepsis was improved with the increase of lentinan concentration. In addition, TNF-α, IL-1β, IL-6, and HMGB1 were decreased with the increase of lentinan concentration, but the expression of IL-10 was increased. Lentinan could also reduce the expression of oxidative stress injury indexes and liver function indexes and inhibit bacterial translocation to liver and lung tissues. Further mechanism investigation revealed that lentinan downregulated the expression of the NF-κB signaling pathway molecules (NF-κB, TLR4, and Bax) and upregulated the expression of occludin and Bcl-2. In conclusion, lentinan inhibits the activity of the NF-κB signaling pathway, thus attenuating injuries of small intestinal mucosa and liver and lung in mice with gut-origin sepsis and reducing the inflammatory response in the process of sepsis.


2004 ◽  
Vol 107 (3) ◽  
pp. 281-289 ◽  
Author(s):  
Jayasree BASIVIREDDY ◽  
Molly JACOB ◽  
Kunissery A. BALASUBRAMANIAN

The use of NSAIDs (non-steroidal anti-inflammatory drugs), although of great therapeutic value clinically, is limited by their tendency to cause mucosal damage in the gastrointestinal tract. In the small intestine, the effects these drugs have been shown to produce include inhibition of cyclo-oxygenase, mitochondrial dysfunction and free radical-induced oxidative changes, all of which contribute to the mucosal damage seen. Glutamine is a fuel preferentially used by enterocytes and is known to contribute to maintaining the integrity of these cells. In the present study, we investigated the effect of glutamine on indomethacin-induced changes in the small intestinal mucosa. Rats were given 2% glutamine or glutamic acid or isonitrogenous amino acids, glycine or alanine, in the diet for 7 days. Indomethacin was then administered orally at a dose of 40 mg/kg of body weight. After 1 h, the small intestine was removed and used for the measurement of parameters of oxidative stress and mitochondrial and BBM (brush border membrane) function. Evidence of oxidative stress was found in the mucosa of the small intestine of drug-treated rats, as indicated by significantly increased activity of xanthine oxidase (P<0.001) and myeloperoxidase (P<0.001), with corresponding decreases in the levels of several free radical scavenging enzymes and α-tocopherol (P<0.001 in all cases). Levels of products of peroxidation were also significantly elevated (P<0.001 for all the parameters measured). In addition, oxidative stress was evident in isolated intestinal mitochondria and BBMs (P<0.001 for all the parameters measured), with associated alterations in function of these organelles (P<0.001 for all the parameters measured). Supplementation of the diet with glutamine or glutamic acid prior to treatment with indomethacin produced significant amelioration in all the effects produced by the drug in the small intestine (P<0.001 for all the parameters measured). Glycine and alanine were found to be much less effective in these respects.


1985 ◽  
Vol 104 (2) ◽  
pp. 435-443 ◽  
Author(s):  
A. N. Janes ◽  
T. E. C. Weekes ◽  
D. G. Armstrong

SummaryTwo groups of six sheep were fed either dried-grass or ground maize-based diets for at least 4 weeks before slaughter. Samples of the small intestinal mucosa and spancreatic tissue were assayed for a-amylase, glucoamylase, maltase and oligo-l,6-glucosidase.The pancreatic tissue contained high activities of α-amylase and much lower activities of glucoamylase, maltase and oligo-1,6-glucosidase. There was no effect of diet on the specific activities of any of these enzymes in the pancreatic tissue.The activity of α-amylase adsorbed on to the mucosa of the small intestine was greatest in the proximal region of the small intestine, the activity generally declining with increasing distance away from the pylorus. There was no diet effect on the absorbed α-amylase activity.Similar patterns of distribution along the small intestine were observed for maltase, glucoamylase and oligo-1,6-glucosidase with the highest activities in t he jejunum. There was no overall effect of diet on glucoamylase or maltase specific activities and glucoamylase total activity, although the total activities of maltase and oligo-1,6-glucosidase were significantly greater for the sheep fed the ground maize-based diet (P < 0·05).It is suggested that ruminant animals may be capable of digesting large amounts of starch in the small intestine through an adaptation in the activity of the host carbohydrases.


2015 ◽  
Vol 139 (6) ◽  
pp. 791-795 ◽  
Author(s):  
Stephen Lagana ◽  
Susan Hsiao ◽  
Fei Bao ◽  
Antonia Sepulveda ◽  
Roger Moreira ◽  
...  

Context HepPar-1 and Arginase-1 are urea cycle enzymes used to distinguish hepatocellular carcinoma from other carcinomas. HepPar-1, but not Arginase-1, is known to be immunoreactive with normal human small intestine. Objectives To better define and compare the immunohistochemical staining patterns of HepPar-1 and Arginase-1 in adenocarcinomas arising in the small intestine, including the ampullary region. Design Staining for HepPar-1 and Arginase-1 was performed on 20 nonampullary small intestinal adenocarcinomas and 32 adenocarcinomas from the ampullary region. Ampullary adenocarcinomas were divided into intestinal morphology (15), pancreatobiliary morphology (14), and unclassifiable (3). Nonneoplastic small intestinal mucosa and colorectal adenocarcinomas were used as control groups. Results HepPar-1 stained 12 of 20 nonampullary small intestinal adenocarcinomas, with a median of 63% of cells staining in positive cases. It also stained 11 of 15 ampullary carcinomas with intestinal morphology, with a median of 75% of cells staining in positive cases. Two of 14 ampullary carcinomas with pancreatobiliary morphology were positive for HepPar-1. Arginase-1 showed positivity in 2 ampullary region carcinomas and diffuse positivity in 1 duodenal adenocarcinoma. Two of 22 colorectal carcinomas stained for HepPar-1 with none positive for Arginase-1. Conclusions HepPar-1, but not Arginase-1, usually shows positivity in small intestinal adenocarcinomas and ampullary adenocarcinomas with intestinal morphology, but only rarely shows positivity in ampullary adenocarcinomas with pancreatobiliary morphology. HepPar-1 positivity in metastatic adenocarcinoma with intestinal morphology is suggestive of an upper gastrointestinal primary site.


2011 ◽  
Vol 300 (1) ◽  
pp. E188-E194 ◽  
Author(s):  
Juan C. Marini ◽  
Bettina Keller ◽  
Inka Cajo Didelija ◽  
Leticia Castillo ◽  
Brendan Lee

The synthesis of citrulline from arginine in the small intestine depends on the provision of ornithine. To test the hypothesis that arginase II plays a central role in the supply of ornithine for citrulline synthesis, the contribution of dietary arginine, glutamine, and proline was determined by utilizing multitracer stable isotope protocols in arginase II knockout (AII−/−) and wild-type (WT) mice. The lack of arginase II resulted in a lower citrulline rate of appearance (121 vs. 137 μmol·kg−1·h−1) due to a reduced availability of ornithine; ornithine supplementation was able to restore the rate of citrulline production in AII−/− to levels comparable with WT mice. There were significant differences in the utilization of dietary citrulline precursors. The contribution of dietary arginine to the synthesis of citrulline was reduced from 45 to 10 μmol·kg−1·h−1 due to the lack of arginase II. No enteral utilization of arginine was observed in AII−/− mice (WT = 25 μmol·kg−1·h−1), and the contribution of dietary arginine through plasma ornithine was reduced in the transgenic mice (20 vs. 13 μmol·kg−1·h−1). Dietary glutamine and proline utilization were greater in AII−/− than in WT mice (20 vs. 13 and 1.4 vs. 3.7 μmol·kg−1·h−1, respectively). Most of the contribution of glutamine and proline was enteral rather than through plasma ornithine. The arginase isoform present in the small intestinal mucosa has the role of providing ornithine for citrulline synthesis. The lack of arginase II results in a greater contribution of plasma ornithine and dietary glutamine and proline to the synthesis of citrulline.


2019 ◽  
Vol 149 (12) ◽  
pp. 2164-2173 ◽  
Author(s):  
Roger Yazbeck ◽  
Ruth J Lindsay ◽  
Mark S Geier ◽  
Ross N Butler ◽  
Gordon S Howarth

ABSTRACT Background Prebiotics selectively stimulate the growth of beneficial bacteria within the gastrointestinal tract, and have been investigated in human and animal studies for their capacity to improve intestinal health. Objective We investigated the prebiotics fructo-oligosaccharide (FOS), galacto-oligosaccharide (GOS), and mannan-oligosaccharide (MOS) for their potential to alleviate intestinal damage in rats. Methods Female Dark Agouti rats (6–8 wk old, 110–150 g) were allocated to 1 of the following treatment groups (n = 8/group): saline/water, saline/FOS, saline/GOS, saline/MOS, 5-fluorouracil (5FU)/water, 5FU/FOS, 5FU/GOS, and 5FU/MOS. Rats were pretreated with either 5% GOS, MOS, or FOS or vehicle (water) from day −12 to day 0. On day 0, rats received a single intraperitoneal injection of saline or 5FU. Metabolic data were recorded daily and all rats were killed on day 3. Histopathology was quantified in hematoxylin and eosin–stained sections. Intestinal sucrase and myeloperoxidase activity were quantified by biochemical assay. Fecal SCFAs—acetic, propionic, and butyric acid—were also measured. Statistical analysis was by repeated-measures, 2-factor ANOVA or Kruskal–Wallis and Mann–Whitney U test; P < 0.05 was considered statistically significant. Results Body weight was significantly decreased in all treatment groups after 5FU injection, with no change in body weight observed in any prebiotic treatment group. Total food intake was lower by ≥7% in the GOS treatment group pre-5FU than in all other groups (P < 0.05). Ileal villus height was 18% higher in GOS-treated rats pre-5FU than in respective water controls (P < 0.05). Jejunal and ileal villus height and crypt depth were significantly decreased in all treatment groups after 5FU injection, with no prebiotic effect observed. SCFAs were differentially increased in prebiotic treatment groups compared with water-only controls (P < 0.05). Conclusions FOS, GOS, and MOS have differential effects in modifying small intestinal pathology and SCFA profiles in rats with healthy and damaged small intestinal mucosa.


2008 ◽  
Vol 53 (No. 10) ◽  
pp. 525-532 ◽  
Author(s):  
R. Zitnan ◽  
J. Voigt ◽  
S. Kuhla ◽  
J. Wegner ◽  
A. Chudy ◽  
...  

The objective of this study was to investigate rumen fermentation, apparent digestibility of nutrients, and morphology of ruminal und intestinal mucosa in two cattle breeds of different metabolic type. From each breed six purebred German Holstein (H) bulls representing the secretion type and six Charolais (CH) bulls representing the accretion type were raised and fattened under identical conditions with <I>semi ad libitum</I> feeding of a high energy diet. The animals were used for a digestion trial started at nine months of age and animals were slaughtered at 18 months of age. Body weight (668 vs. 764 kg, <I>P</I> = 0.011), body weight gain (1 223 vs. 1 385 g/day, <I>P</I> = 0.043), and body protein gain (93 vs. 128 g/day, <I>P</I> = 0.001) were lower in H compared to CH bulls. Protein expense per kg protein accretion was higher in H bulls (13.8 vs. 10.2, <I>P</I> = 0.001). No significant differences were found in concentration and pattern of ruminal short chain fatty acid and in apparent digestibility of organic matter, crude fibre, and N-free extracts. There were no significant differencs in all morphometric traits of rumen mucosa between both cattle breeds. Compared to H, the villi of CH bulls were higher in duodenum (586 vs. 495 &mu;m, <I>P</I> = 0.001) and proximal jejunum (598 vs. 518&mu;m, <I>P</I> < 0.001), the crypt were deeper in duodenum (295 vs. 358, <I>P</I>< 0.001) and proximal jejunum (292 vs. 344 &mu;m, <I>P</I> = 0.020). In contrast, the villi in ileum were higher in H (522 vs. 471 &mu;m, <I>P</I> = 0.006). The weight of total small intestine, as percentage of total body weight, was 1.1 in H and 0.8 in CH (<I>P</I> = 0.002). The utilization of food crude protein was positively related to the duodenal (<I>P</I> = 0.001) and proximal jejunal villus height (<I>P</I> = 0.003) and to the duodenal crypt depth (<I>P</I> < 0.001) and negatively related to weight of small intestine (<I>P</I> = 0.004). It is concluded, that the higher growth potential and feed efficiency in CH bulls compared to H bulls is not caused by differences in digestion processes, but in size of small intestine, and morphology of small intestinal mucosa. Obviously the duodenum and proximal jejunum of CH bulls adapt to increase the absorptive surface due to the increase in nutrient demand.


1995 ◽  
Vol 42 (3) ◽  
pp. 297-299
Author(s):  
L P Arciuch ◽  
A Omasta ◽  
K Rostkowska ◽  
M Gałazyn-Sidorczuk ◽  
J Moniuszko-Jakoniuk ◽  
...  

Inhibition by ethanol of the activities of lysosomal exoglycosidases in stomach, small intestine, liver and brain of rats exposed to cadmium (Cd2+) was determined. Out of the glycosidases tested the most distinct effect of Cd2+ and ethanol administered to the rats in vivo was observed in the small intestinal mucosa in a decreasing order: N-acetyl-beta-hexosaminidase, beta-galactosidase and alpha-fucosidase.


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