scholarly journals The Relative Importance of the Small Intestine and the Liver in Phase II Metabolic Transformations and Elimination of p-Nitrophenol Administered in Different Doses in the Rat

2020 ◽  
Vol 88 (4) ◽  
pp. 51
Author(s):  
Attila Almási ◽  
Pál Perjési ◽  
Emil Fischer

Intestinal and hepatic function have been investigated in phase II metabolic reactions and elimination of p-nitrophenol (PNP) in the rat. A jejunal loop was cannulated and recirculated with isotonic solutions containing PNP in different concentrations (0, 20, 100, 500, 1000 µM). Samples were obtained from the perfusate at given intervals. To investigate the metabolic and excretory functions of the liver, the bile duct was cannulated, and the bile was collected. Metabolites of PNP were determined by validated HPLC (high pressure liquid chromatography) methods. The results demonstrated the relative importance of the small intestine and the liver in phase II metabolic transformations and elimination of PNP. There were significant differences between the luminal and biliary appearances of p-nitrophenol-glucuronide (PNP-G) and p-nitrophenol–sulfate (PNP-S). The PNP-G appeared in the intestinal lumen at the lower PNP concentrations (20 µM and 100 µM) at higher rate than in the bile. No significant difference was found between the intestinal and the biliary excretion of PNP-G when PNP was administered at a concentration of 500 µM. However, a reverse ratio of these parameters was observed at the administration of 1000 µM PNP. The results indicated that both the small intestine and the liver might play an important role in phase II metabolic reactions and elimination of PNP. However, the relative importance of the small intestine and the liver can be dependent on the dose of drugs.

1973 ◽  
Vol 44 (6) ◽  
pp. 583-594 ◽  
Author(s):  
R. F. Crampton ◽  
Maria T. Lis ◽  
D. M. Matthews

1. Though mucosal uptake of peptides plays an important part in protein absorption, little is known about the site of maximal absorption of peptides in the small intestine. This paper reports an investigation of the characteristics of absorption and hydrolysis of l-methionyl-l-methionine (Met-Met) and glycylglycine (Gly-Gly) by tied loops along the length of the small intestine of the rat, and those of absorption of the equivalent l-methionine (Met) and glycine (Gly). 2. Absorption of Met-Met, or a mixture of Met-Met and Met, was maximal in the proximal half of the small intestine, whereas absorption of Met was maximal in the distal half. Absorption of Met-Met was greater than that of the equivalent Met, especially in the proximal small intestine. In most sites, absorption of a mixture of Met-Met and Met was not significantly different from that of the equivalent Met-Met. Absorption of Met was not increased by raising its concentration from 100 to 200 μmol/ml, but addition of Met-Met (50 μmol/ml) produced a large increase in absorption, indicating that absorption of Met from Met-Met is independent of that from free Met. During absorption of Met-Met, large amounts of free Met appeared in the intestinal lumen. Most of this resulted from intralumen hydrolysis. The hydrolytic ability of mucosal homogenates was several times greater than that required to hydrolyse the Met-Met disappearing from the lumen during absorption. 3. The sites of maximal absorption of Gly-Gly, Gly and a mixture of Gly-Gly and Gly, were all in the proximal half of the intestine near the mid-point. Absorption of Gly-Gly was greater than that of the equivalent Gly, especially in the proximal sites. In several sites, there was no significant difference between absorption of a mixture of Gly-Gly and Gly and that of the equivalent Gly-Gly. During absorption of Gly-Gly, the amounts of free Gly appearing in the lumen were small except in the two most distal sites. Most of the free Gly resulted from back-diffusion from the mucosa. The hydrolytic ability of mucosal homogenates was barely adequate to hydrolyse the Gly-Gly disappearing from the lumen during absorption. 4. The results suggest that there is no real discrepancy between the site of maximal absorption of protein digestion products from tied loops of small intestine and that of their absorption in the intact animal. They indicate that absorption of Met and Met-Met involves independent mechanisms, and confirm previous evidence that the capacity of the intestine to absorb mixtures of peptides and amino acids is greater than its capacity to absorb amino acids alone.


Author(s):  
А.А. Коваленко ◽  
Г.П. Титова ◽  
В.К. Хугаева

Оперативное лечение различных заболеваний кишечника сопровождается осложнениями в виде нарушений микроциркуляции в области анастомоза кишки. Ранее нами показана способность лимфостимуляторов пептидной природы восстанавливать нарушенную микроциркуляцию, что послужило основой для настоящего исследования. Цель работы - оценка влияния стимуляции лимфотока в стенке кишки на процессы восстановления микроциркуляции, структуры и функции тонкой кишки в области оперативного вмешательства. Методика. В экспериментах на наркотизированных крысах (хлоралгидрат в дозе 0,6 г/кг в 0,9% растворе NaCl) моделировали различные поражения тонкой кишки (наложение лигатуры, перевязка 1-3 брыжеечных артерий, перекрут петли кишки вокруг оси брыжейки, сочетание нескольких видов повреждений). Резекция поврежденного участка через 1 сут. с последующим созданием тонкокишечного анастомоза завершалась орошением операционного поля раствором пептида-стимулятора лимфотока (40 мкг/кг массы животного в 1 мл 0,9% раствора NaCl). На 7-е сут. после операции проводили гистологическое исследование фрагмента кишки в области анастомоза. Результаты. На 7-е сут. после резекции у выживших животных (летальность вследствие кишечной непроходимости составляла 30%) имеют место морфологические признаки острых сосудистых нарушений стенки кишки, изменений кровеносных и лимфатических микрососудов, интерстициальный отек всех слоев стенки кишки, дилатация просвета кишки, повреждение всасывающего эпителия ворсин с истончением щеточной каемки клеток, морфологические признаки гиперфункции бокаловидных клеток. Использование лимфостимулятора пептидной природы после операции увеличивало выживаемость животных на 24%. У части животных отмечалось уменьшение расширения просвета кишки, у других практически полная его нормализация. Восстанавливалась форма кишечных ворсин и распределение бокаловидных клеток. Отсутствовали признаки внутриклеточного и межмышечного отека. Отмечено умеренное полнокровие венул. Заключение. Использование лимфостимулятора при хирургическом лечении кишечной непроходимости увеличивает выживаемость животных на 24% по сравнению с контролем, способствует более раннему восстановлению структуры и функции тонкой кишки. Полученные результаты свидетельствуют о перспективности использования стимуляции лимфотока при операциях на кишечнике. Surgical treatment of bowel diseases is associated with complications that cause microcirculatory disturbances in the anastomosis area and may lead to a fatal outcome. This study was based on our previous finding that peptide-type lymphatic stimulators are able to restore impaired microcirculation. The aim of this work was stimulating the lymph flow in the intestinal wall to facilitate recovery of microcirculation, structure and function of the small intestine in the area of surgical intervention. Methods. In experiments on anesthetized rats (0.6 g/kg chloral hydrate in 0.9% NaCl), various small bowel lesions were modeled (bowel ligation, ligation of 1-3 mesenteric arteries, gut torsion, combination of several lesion types). In 24 h, the damaged area was resected, and a small intestine anastomosis was creased. The surgery was completed with irrigation of the operative field with a solution of lymph flow stimulating peptide (40 мg/kg body weight in 1 ml of 0.9% NaCl). A gut fragment from the anastomosis area was examined histologically on day 7 after the surgery. Results. On the 7th day after removing the intestinal obstruction, the surviving animals (lethality 30%) had morphological signs of acute vascular disorders in the intestinal wall; changes in blood and lymphatic microvessels; interstitial edema of all intestinal wall layers; dilatation of the intestinal lumen; damage to the absorptive epithelium of villi with thinning of the brush border, and hyperfunction of mucous (goblet) cells. The use of the peptide after surgery increased the survival rate of animals by 24% and provided a smaller dilatation of the intestinal lumen in some animals. In other animals, the lumen recovered. The shape of intestinal villi and distribution of goblet cells were restored. Signs of intracellular and intermuscular edema were absent. Moderate venular congestion was noticed. Conclusion. Using the lymphatic stimulator in surgical treatment of intestinal obstruction increases the survival rate of animals by 24% compared to the control, facilitates earlier restoration of the small intestine structure and function. The obtained results indicated the effectiveness of lymphatic stimulation in intestinal surgery.


Marine Drugs ◽  
2021 ◽  
Vol 19 (1) ◽  
pp. 23
Author(s):  
M. Carmen Louzao ◽  
Paula Abal ◽  
Celia Costas ◽  
Toshiyuki Suzuki ◽  
Ryuichi Watanabe ◽  
...  

Okadaic acid (OA) and its main structural analogs dinophysistoxin-1 (DTX1) and dinophysistoxin-2 (DTX2) are marine lipophilic phycotoxins distributed worldwide that can be accumulated by edible shellfish and can cause diarrheic shellfish poisoning (DSP). In order to study their toxicokinetics, mice were treated with different doses of OA, DTX1, or DTX2 and signs of toxicity were recorded up to 24 h. Toxin distribution in the main organs from the gastrointestinal tract was assessed by liquid chromatography-mass spectrometry (LC/MS/MS) analysis. Our results indicate a dose-dependency in gastrointestinal absorption of these toxins. Twenty-four hours post-administration, the highest concentration of toxin was detected in the stomach and, in descending order, in the large intestine, small intestine, and liver. There was also a different toxicokinetic pathway between OA, DTX1, and DTX2. When the same toxin doses are compared, more OA than DTX1 is detected in the small intestine. OA and DTX1 showed similar concentrations in the stomach, liver, and large intestine tissues, but the amount of DTX2 is much lower in all these organs, providing information on DSP toxicokinetics for human safety assessment.


Animals ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 660
Author(s):  
Edoardo Bardi ◽  
Martina Manfredi ◽  
Raffaella Capitelli ◽  
Emanuele Lubian ◽  
Alessandro Vetere ◽  
...  

The use of long-acting gonadotropin-releasing hormone (GnRH) agonists to suppress fertility has been poorly investigated in reptiles, and the few available studies show inconsistent results. The efficacy of single and double intramuscular 4.7 mg deslorelin acetate implants in captive pond sliders (Trachemys scripta) was investigated, with 20 animals divided into three groups: a single-implant group (6 animals), a double-implant group (6 animals), and a control group (no implant). During one reproductive season (March to October), plasmatic concentration of sexual hormones (estradiol, progesterone, and testosterone) and ovarian morphometric activity via computed tomography were monitored about every 30 days. A significative decrease in the number of phase II ovarian follicles was detected in the double-implant group compared with the control group, but no significant difference was noted in the number of phase III and phase IV follicles, egg production, and plasmatic concentration of sexual hormones. Results show that neither a single nor a double deslorelin acetate implant can successfully inhibit reproduction in female pond sliders during the ongoing season, but the lower number of phase II follicles in the double-implant group can possibly be associated with reduced fertility in the following seasons.


Author(s):  
Kusmardi Kusmardi ◽  
Arif Ramadhan Tamzir ◽  
Santi Widiasari ◽  
Ari Estuningtyas

Objective: The incidence of small intestine cancer (SIC) is rising despite available preventive measures. Kaempferol and quercetin are a potential chemopreventive agent for SIC, but in vivo findings are inconclusive. We aim to study the effects of kaempferol and quercetin on colitis-associated small intestine carcinogenesis in mice.Methods: Suppression effect was tested using mice divided into 6 groups of treatment, i.e.; normal (N) group, negative control (NC), leaf extract (medium dose [MD]) dose 12.5 and 25 mg/kg body weight (BW), leaf extract chitosan and nanoparticle of mahkota dewa (NPMD) dose 6.25 and 12.5 mg/kg BW. Dextran sulfate sodium induction of 1% w/v was administered through drinking water for 6 weeks of treatment. The suppression effect was observed histopathologically by counting the mitotic cells and hyperplasia cells of the crypt of small intestine with hematoxylin-eosin staining.Results: Mitosis cells mean of NC group was not significant difference either with MD 12.5 (p=0.394) or MD 6.5 (p=0.310). However, mitosis cell mean appears to be lower in the NPMD 12.5 (p=0.09) and NPMD 6.25 (p=0.05) groups than the NC group. There was a significant difference among the mean of hyperplasia NC group and MD and also NPMD group. Significant difference also can be showed between MD 12.5 and MD 25 (p=0.026), and between NPMD 6.25 and NPMD 12.5 (p=0.002), and between MD 12.5 and NPMD 12.5 (p=0.002).Conclusion: Our results demonstrate suppression of hyperplasia small intestine by either nanoparticle or extract of Phaleria macrocarpa extracts. The suppression of mitosis was showed by administration of nanoparticle.


1990 ◽  
Vol 259 (3) ◽  
pp. G443-G452 ◽  
Author(s):  
L. C. Read ◽  
A. P. Lord ◽  
V. Brantl ◽  
G. Koch

beta-Casomorphins (beta-CMs) derived from milk beta-casein may exert various opiate activities in milk-fed infants. To assess the physiological significance of beta-CMs as a source of circulating opioids in infants, we measured absorption rates of several beta-CMs under near-physiological conditions using in situ autoperfused lamb intestine. The naturally occurring beta-CMs, beta-CM-7 and beta-CM-4-amide, were absorbed readily into blood with no transfer into lymph. Uptake peaked within several minutes of the luminal infusion of peptide but then declined sharply and stopped within a further 10-15 min. The recovery in blood, intestinal contents, and tissue at the end of the 30-min experiment was less than 1% of the infused dose. The low recovery was due to rapid proteolysis based on in vitro studies that demonstrated half-lives of less than 5 min in lamb blood, luminal contents, and lymph. The synthetic dipeptidyl peptidase IV-resistant analogue beta-[D-Ala2]CM- 4-amide was stable during incubation in blood, lymph, or luminal contents and was absorbed into blood at rates that were maximal within several minutes and remained steady for the 30-min period. We conclude that although natural beta-CMs are transferred across the lamb small intestine, rapid degradation within the intestinal lumen, gut epithelium, and blood would prevent entry into the circulation under normal conditions. Val-beta-CM-7, a putative stable precursor, had similar stability and kinetics of absorption to beta-CM-7, results that exclude Val-beta-CM-7 as a stable precursor for delivery of beta-CMs to the circulation. Essentially identical results to those in lambs were obtained in 7-day-old piglets.


2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P57-P57
Author(s):  
Drew M Horlbeck ◽  
Herman A Jenkins ◽  
Ben J Balough ◽  
Michael E Hoffer

Objective The efficacy of the Otologics Fully Implantable Hearing Device (MET) was assessed in adult patients with bilateral moderate to severe sensorineural hearing loss. Methods Surgical insertion of this totally implanted system was identical to the Phase I study. A repeated-measures within-subjects design assessed aided sound field thresholds and speech performances with the subject's own, appropriately fit, walk-in hearing aid(s) and the Otologics Fully Implantable Hearing Device. Results Six- and 12-month Phase II data will be presented. Ten patients were implanted and activated as part Phase II clinical trial. Three patients were lost to long term follow-up due to two coil failures and one ossicular abnormality preventing proper device placement. No significant differences between preoperative (AC = 59 dB, BC = 55 dB) and postoperative (AC = 61 dB, BC = 54 dB) unaided pure tone averages were noted (p < 0.05). Pure tone average implant aided thresholds (41 dB) were equivalent to that of walk-in-aided (37 dB) condition with no significant difference (p < 0.05) between patients’ walk-in-aided individual frequency thresholds and implant-aided thresholds. Word recognition scores and hearing in noise scores were similar between the walk-in-aided and for the implant-aided condition. Patient benefit scales will be presented at all end points. Conclusions Results of the Otologics MET Fully Implantable Hearing Device Phase II trial provide evidence that this fully implantable device is a viable alternative to currently available hearing aids in patients with sensorineural hearing loss.


1979 ◽  
Vol 57 (7) ◽  
pp. 688-694 ◽  
Author(s):  
A. K. Singh ◽  
E. W. Banister

Adrenalectomized rats exposed to high pressure oxygen (OHP) until convulsion convulse much later than sham-operated or normal rats. No significant changes in the concentration of noradrenaline (NA) and total catecholamines (TC) in the brain were noted in sham-operated or adrenalectomized rats resulting from sham or real surgery and no change occurred in these variables in normal sham-operated or adrenalectomized animals after OHP leading to convulsion. Brain adrenaline (A) concentration, however, decreased significantly in all three groups following OHP-induced convulsions. Activity of catecholamine O-methyltransferase (COMT) decreased significantly only in adrenalectomized rats. Brain γ-aminobutyric acid (GABA), glutamate, and other amino acid level remained unchanged after adrenalectomy whereas the concentration of ammonia decreased significantly when normal rats were adrenalectomized. After OHP-induced convulsions, the concentrations of brain GABA and glutamate decreased and ammonia and glutamine plus asparagine increased significantly in normal, sham-operated, and adrenalectomized rats. In the blood no significant difference was noted in the concentration of the catecholamines, ammonia, and amino acids either in normal or sham-operated rats. In adrenalectomized rats, the blood A and NA concentrations decreased significantly and tyrosine increased significantly. The concentration of NA, ammonia, and glutamine plus asparagine in rats from all three groups increased after OHP-induced convulsions, whereas the concentration of glutamate decreased significantly. Since the concentration of A increased significantly after convulsions in normal and sham-operated rats but did not change in adrenalectomized rats, it might be proposed that adrenalectomy protects against OHP-induced convulsions by reducing the circulating concentration of A and ammonia.However, these are not the only factors involved in the protection since the sham-operated rats also convulsed much later than normal rats but had similar ammonia and A concentrations to normal animals.


1968 ◽  
Vol 22 (2) ◽  
pp. 237-246 ◽  
Author(s):  
Aileen M. Lennox ◽  
A. K. Lough ◽  
G. A. Garton

1. Total lipids were extracted from digesta obtained from the rumen, abomasum and upper small intestine (jejunum) of each of four slaughtered sheep. The lipids were fractionated into unesterified fatty acids, neutral lipids and phospholipids and the proportional contribution of each fraction to the total fatty acids was determined.2. The contribution made by phospholipids to the total fatty acids in the digesta showed a marked increase in the samples from the small intestine compared with those from the rumen and abomasum. This increase was apparently due to the presence of biliary phospholipids.3. Total lipids and conjugated bile acids were extracted from sheep bile, the lipids were fractionated and their fatty-acid composition was determined. Phospholipids predominated and these consisted mainly of phosphatidylcholine, together with some lysophosphatidylcholine.4. Both phospholipids contained significant amounts of unsaturated C18 components which could account, at least in part, for the previously reported increament to the proportion of these acids in the digesta when it enters the upper jejunum.5. The overall fatty acid compositions of the two biliary phospholipids were very similar and, in common with other naturally occurring phosphatidylcholines, the fatty acids present in position 2 of the phosphatidylcholine of bile were found to consist almost entirely of unsaturated components.6. Total lipids and conjugated bile acids were extracted from samples of digesta obtained from three sheep with cannulas in different positions in the jejunum. Analysis of the lipids indicated that biliary phospholipids, in particular phosphatidylcholine, underwent progressive hydrolysis in the intestinal lumen.7. The distribution of conjugated bile acids, unesterified fatty acids and phospholipids between the solid (particulate) and liquid (micellar) phases of the intestinal digesta was determined. These chyme constituents were, for the most part, associated with the particulate matter and thus, at any given time, it appears that only a small fraction of the total fatty acids is available for absorption in micellar form. It is suggested that the micellar solubilization of fatty acids may be facilitated by the presence of lysophosphatidylcholine.


2000 ◽  
Vol 278 (4) ◽  
pp. G604-G616 ◽  
Author(s):  
K. Indireshkumar ◽  
James G. Brasseur ◽  
Henryk Faas ◽  
Geoffrey S. Hebbard ◽  
Patrik Kunz ◽  
...  

The relative contributions to gastric emptying from common cavity antroduodenal pressure difference (“pressure pump”) vs. propagating high-pressure waves in the distal antrum (“peristaltic pump”) were analyzed in humans by high-resolution manometry concurrently with time-resolved three-dimensional magnetic resonance imaging during intraduodenal nutrient infusion at 2 kcal/min. Gastric volume, space-time pressure, and contraction wave histories in the antropyloroduodenal region were measured in seven healthy subjects. The subjects fell into two distinct groups with an order of magnitude difference in levels of antral pressure activity. However, there was no significant difference in average rate of gastric emptying between the two groups. Antral pressure history was separated into “propagating high-pressure events” (HPE), “nonpropagating HPEs,” and “quiescent periods.” Quiescent periods dominated, and average pressure during quiescent periods remained unchanged with decreasing gastric volume, suggesting that common cavity pressure levels were maintained by increasing wall muscle tone with decreasing volume. When propagating HPEs moved to within 2–3 cm of the pylorus, pyloric resistance was found statistically to increase with decreasing distance between peristaltic waves and the pylorus. We conclude that transpyloric flow tends to be blocked when antral contraction waves are within a “zone of influence” proximal to the pylorus, suggesting physiological coordination between pyloric and antral contractile activity. We further conclude that gastric emptying of nutrient liquids is primarily through the “pressure pump” mechanism controlled by pyloric opening during periods of relative quiescence in antral contractile wave activity.


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