Rat Gastrointestinal Tract Research Articles

Improvement effects of a novel Chinese herbal formula in imiquimod and IL-23-stimulated mouse models of psoriasis

BackgroundPsoriasis is a long-term inflammatory skin disease. A novel herbal formula containing nine Chinese herbal medicines, named Inflammation Skin Disease Formula (ISDF), has been prescribed in clinics for decades.AimsTo investigate the efficacy and action mechanisms of ISDF on psoriasis using imiquimod (IMQ) and Interleukin-23 (IL-23)-induced models in mice and reveal the pharmacokinetics profile of ISDF in rats.MethodsTopical administration of IMQ and intradermal injection with IL-23 respectively induced skin lesions like psoriasis on the dorsal area of Balb/c and C57 mice. The mice's body weight, skin thickness, and psoriasis area and severity index (PASI) were assessed weekly. SD rats were used in the pharmacokinetics study and the contents of berberine and baicalin were determined.ResultsThe PASI scores and epidermal thickness of mice were markedly decreased after ISDF treatment in both models. ISDF treatment significantly decreased the contents of IL-17A and IL-22 in the serum of IMQ- and IL-23-treated mice. Importantly, ISDF markedly downregulated IL-4, IL-6, IL-1β, and tumor necrosis factor α (TNF-α) gene expression, and the phosphorylation of NF-κB p65, JNK, ERKs and MAPK p38 in IMQ-treated mice. The protein phosphorylation of Jak1, Jak2, Tyk2 and Stat3 was significantly mitigated in the ISDF-treated groups. The absorption of baicalin and berberine of ISDF through the gastrointestinal tract of rats was limited, and their distribution and metabolism in rats were also very slow, which suggested ISDF could be used in the long-term application.ConclusionsISDF has a strong anti-psoriatic therapeutic effect on mouse models induced with psoriasis through IMQ and IL-23, which is achieved by inhibiting the activation of the Jak/Stat3-activated IL-23/Th17 axis and the downstream NF-κB signalling and MAPK signalling pathways. ISDF holds great potential to be a therapy for psoriasis and should be further developed for this purpose.

Yeast protein: In vivo gastrointestinal digestion and biochemical characteristics

In this study, the digestion of yeast protein in the gastrointestinal tract of rats, and its effects on the blood biochemical parameters at different time points were investigated. Yeast protein was digested into peptides by pepsin in the stomach, broken down into dipeptides or amino acids by trypsin in the small intestine, and then absorbed by the rats or entered the colon. The peptide levels in gastric, small intestinal, and large intestinal digesta reached the highest level at 4 h, 2 h, and 8 h, respectively. Intact yeast protein in the gastric tract was found within 4 h, and no intact protein was present in intestinal digesta. Compared with gastric digesta, yeast protein intestinal digesta had much less distinguish and distinct stripes. Yeast protein ingestion increased the levels of immunoglobulin, high-density lipoprotein, and uric acid, and decreased the levels of total cholesterol, triglycerides, and low-density lipoprotein, while it did not significantly affect the levels of globulin, albumin, aspartate aminotransferase, and alanine aminotransferase in serum. This study demonstrated the digestion kinetics of yeast protein in the gastrointestinal tract of rats, and its beneficial effects on the blood biochemical parameters of rats and provided scientific evidence for yeast protein as an efficient and sustainable alternative protein source.

Seasonal variation of melatonin secretion across various segments of the gastrointestinal tract in rats

ObjectiveTo investigate whether melatonin (MT) secretion in different parts of the gastrointestinal tract (GIT) exhibits seasonal variations and its correlation with immune regulation. MethodsSixty Sprague-Dawley rats were divided into control and model groups, and the pineal gland was removed in the model group. Stomach, jejunum, ileum, and colon tissues were obtained during the spring equinox, summer solstice, beginning of autumn, autumn equinox, and winter solstice. The levels of MT, MT receptors (MR), arylalkylamine N-acetyltransferase (AANAT), hydroxyindole-O-methyltransferase (HIOMT), interleukin-2 (IL-2), and interleukin-10 (IL-10) in the GIT were measured using enzyme-linked immunosorbent assay. ResultsExcept for the stomach, the jejunum, ileum, and the colon showed seasonal tendencies in MT secretion. In the control group, MT secretion in the jejunum and ileum was the highest in the long summer, and colonic MT secretion was the highest in winter. In the model group, MT levels in the colon were highest in the summer. The seasonal rhythms of the MR, AANAT, HIOMT, IL-2, and IL-10 in the colon were roughly similar to those of MT, and changed accordingly after pinealectomy. ConclusionsGastrointestinal MT secretion is related to seasonal changes, and MT secretion in each intestinal segment is influenced by different seasons. The biological effects of MT in the gut are inextricably linked to the mediation of MR, and a hormone-receptor linkage exists between MT and MR. The effect of seasonal changes on the gastrointestinal immune system may be mediated through the regulation of seasonal secretion of MT.

Evaluation of the feeding safety of Moringa (Moringa oleifera L.) in the Sprague Dawley rat

This study aimed to evaluate the safety of Moringa by comparing the effects of different gavage doses of Moringa. The general behavior, body weight, food intake, blood indexes, serum biochemical indexes, and histopathology of rats were used to determine the safety threshold and to provide a reference for the further development and use of Moringa as animal feed. 40 Sprague Dawley rats were selected and given transoral gavage for 28 consecutive days. The T1, T2 and T3 groups were observed for general behavior, body weight, and food intake. Blood and serum biochemical indices were quantified, and histopathology was performed to evaluate the effect and safety of Moringa. The results of the toxicological test showed that (1) Only T1 groups experienced diarrhea. (2) The body weight and food intake of rats in each group were normal compared with the control group. (3) The hematological and serum biochemical indices of rats in the T1 group were significantly different from those of CK but were in the normal range; (4) The results of microscopic examination of the heart, liver, spleen, lung, and kidney of rats in each group were normal, but inflammation occurred in stomach and jejunum of rats in the T1 group, but not in the ileum. The gastrointestinal tract of rats in the T2 and T3 groups were normal. (5) No abnormal death occurred in any of the treatment groups.The results of this study revealed that gavage of Moringa homogenate at a dose of 6 g/kg BW can cause diarrhea in rats. Although there is no pathological effect on weight, food intake, blood and serum biochemical indicators in rats, there are pathological textures in the gastrointestinal tissue caused by diarrhea. Therefore, the safety threshold of Moringa homogenate should be ≤ 3 g/kg BW.

Pharmacokinetic control of orally dosed cyclosporine A with mucosal drug delivery system.

This study aimed to control the oral absorption of cyclosporine A (CsA) with the use of a mucosal drug delivery system (mDDS). Mucopenetrating nanocarriers (MP/NCs) and mucoadhesive nanocarriers (MA/NCs) were prepared by flash nanoprecipitation employing polystyrene-block-poly(ethylene glycol) and polystyrene-block-poly(N,N-dimethyl aminoethyl methacrylate), respectively. Their particle distribution in the rat gastrointestinal tract were visualized by fluorescent imaging. Plasma concentrations were monitored after oral administration of CsA-loaded MP/NCs (MP/CsA) and MA/NCs (MA/CsA) to rats. MP/NCs and MA/NCs had a particle size below 200nm and ζ-potentials of 4 and 40mV, respectively. The results from in vitro experiments demonstrated mucopenetration of MP/NCs and mucoadhesion of MA/NCs. Confocal laser scanning microscopic images showed diffusion of MP/NCs in the gastrointestinal mucus towards epithelial cells and localization of MA/NCs on the surface of the gastrointestinal mucus layer. In a pH 6.8 solution, rapid and sustained release of CsA were observed for MP/CsA and MA/CsA, respectively. After oral dosing (10 mg-CsA/kg) to rats, amorphous CsA powder exhibited a time to maximum plasma concentration (Tmax) of 3.4h, maximum plasma concentration (Cmax) of 0.12μg/mL, and bioavailability of 0.7%. Compared with amorphous CsA powder, MP/CsA shortened Tmax by 1.1 to 2.3h and increased the bioavailability by 43-fold to 30.1%, while MA/CsA prolonged Tmax by 3.4 to 6.8h with Cmax and bioavailability of 0.65μg/mL and 11.7%, respectively. These pharmacokinetic behaviors would be explained by their diffusion and release properties modulated by polymeric surface modification. The mDDS approach is a promising strategy for the pharmacokinetic control of orally administered CsA.

Resistance of Lactobacillus Sp. SKG 34 in The Digestive Tract of Rats Detected Using Random Amplified Polymorphic DNA Technique

In recent years, interest in probiotics, particularly Lactobacillus strains like Lactobacillus sp. SKG34, isolated from Sumbawa mare milk, has surged due to their potential health benefits. This strain holds promise as a probiotic agent, but understanding its behavior in the gastrointestinal (GI) tract is essential for effective application. This study aimed to investigate the resistance and persistence of Lactobacillus sp. SKG34 in the GI tract of rats. Rats were orally administered the strain at a concentration of 10^8 cells for 30 days. The probiotic’s ability to modulate gut microbiota and improve host health is a key area of interest. By utilizing techniques like PCR-RAPD, this research sought to elucidate the fate of Lactobacillus sp. SKG34 in the complex environment of the rat GI tract. Results revealed a significant increase in LAB population in cecal contents, from 3.06 x 10^9 cfu/g in the control group to 1.25 x 10^10 cfu/g in the probiotic group. RAPD analysis also detected Lactobacillus sp. SKG34 in approximately 23% of the total population of lactic acid bacteria in cecal contents, indicating its resistance and proliferation within the GI tract. Further investigation is warranted to fully understand the potential of Lactobacillus sp. SKG34 as a beneficial probiotic strain for human application.

Insight into the Beneficial Use of Iru An African Condiment from Parkia Biglobosa

The composition and activity of the gut microbiota, which is essential for preserving health, are greatly influenced by the food that humans eat. Iru, a traditional West African fermented condiment, is derived from Parkia biglobosa seeds and is a sought-after ingredient in West African cuisine due to its unique aroma, flavor, and texture. Iru is a spice that adds depth to stews, soups, and sauces in West African cooking, especially in Nigeria and Cameroon. Due to the fermentation process, which transforms complex ingredients into more easily absorbed forms, it has a distinct flavor and fragrance. Beyond only eating, iru has a deep cultural meaning that is frequently emphasized in ceremonies, festivals, and customs. Generations of people have used this fermenting technique. Iru is a traditional condiment from West Africa that showcases the region’s culinary heritage and is a favorite condiment in West African cookery. It is made using beneficial bacteria to make distinctive, tasty, and culturally significant food items. This study investigated the effects of two distinct food components—Maggi Knorr, a chemical seasoning mixture, and Iru (Parkia biglobosa), a traditional fermented condiment from West Africa—on the intestinal microbial communities of mice. Using mice as a well-researched animal model, we will assess the short- and long-term effects of food supplementation with Maggi Knorr and Iru on microbial diversity, composition, and functional ability in the gastrointestinal tract. The metabolic activities of the microbial communities will be characterized by means of high-throughput sequencing of 16S rRNA genes in conjunction with metabolism analysis. This study aimed to investigate how two commonly utilized food additives, namely chemical seasoning (Maggi Star, Knorr and Vedan) and Iru (Parkia biglobosa), affect the microbial community residing in the gastrointestinal tracts of rats.

Dose proportionality and bioavailability of quinoxaline-based JNK inhibitor after single oral and intravenous administration in rats

The dose proportionality and bioavailability of the potential anti-inflammatory and neuroprotective JNK inhibitor 11H-indeno[1,2-b]quinoxalin-11-one oxime (IQ-1) were evaluated by comparing pharmacokinetic parameters after single oral (25, 50 and 100 mg/kg) and intravenous (1 mg/kg) IQ-1 administration in rats. IQ-1 and its major metabolite ketone 11H-indeno[1,2-b]quinoxalin-11-one (IQ-18) were isolated from plasma samples by liquid–liquid extraction. IQ-1 (E-isomer) and IQ-18 were simultaneously quantified in plasma by the validated method of liquid chromatography with triple quadrupole mass spectrometry (HPLC–MS/MS). The absolute bioavailability of IQ-1 was < 1.5%. C max values were 24.72 ± 4.30, 25.66 ± 7.11 and 37.61 ± 3.53 ng/mL after single oral administration of IQ-1 at doses of 25, 50 and 100 mg/kg, respectively. IQ-1 exhibited dose proportionality at 50–100 mg/kg dose levels, whereas its pharmacokinetics was not dose proportional over the range of 25–50 mg/kg. IQ-18 demonstrated the invariance of the dose-normalized Cmax. In this study we systematically elucidated the absorption characteristics of IQ-1 in rat gastrointestinal tract and provided better understanding of IQ-1 pharmacology for the future development of a new formulations and therapeutic optimisation.

Quantitative analysis of gastrointestinal fluid absorption and secretion to estimate luminal fluid dynamics in rats

The drug absorption profile is dependent on the luminal drug concentration, which in turn is influenced by the gastrointestinal (GI) fluid dynamics. In the present study, therefore, we aimed to examine the luminal fluid dynamics by kinetically analyzing fluid absorption and secretion along the GI tract in rats using the in situ closed-loop technique with non-absorbable fluorescein isothiocyanate-dextran 4000 (FD-4) and tritium water labeling ([3H]water) under different osmotic conditions. We found that the luminal fluid volume in the jejunum and ileum, but not the colon, gradually decreased and reached a steady state. In contrast, [3H]water almost completely disappeared in all intestinal regions. Kinetic analysis revealed the following rank order for the rate constant of fluid secretion: jejunum > ileum > colon, whereas a negligible regional difference was observed in the rate constant of fluid absorption. Fluid secretion under an isosmotic condition (300 mOsm/kg) was higher than that at 0 mOsm/kg in all intestinal regions, though no significant changes in fluid absorption were observed. Thus, the fluid secretion process appears to be the major determinant of the regional differences in GI fluid dynamics. Our findings indicate that the luminal fluid volume is altered as a result of water ingestion, absorption, and secretion, and finally reaches an apparent steady state, which is regulated mainly by the process of fluid secretion.

Evaluation of the Safety and Gastrointestinal Migration of Guanidinylated Chitosan after Oral Administration to Rats.

Arginine-rich membrane-permeable peptides (APPs) can be delivered to cells by forming complexes with various membrane-impermeable bioactive molecules such as proteins. We recently reported on the preparation of guanidinylated chitosan (GCS) that mimics arginine peptides, using chitosan, a naturally occurring cationic polysaccharide, and confirmed that it enhances protein permeability in an in vitro cell system. However, studies on the in vivo safety of GCS are not available. To address this, we evaluated the in vivo safety of GCS and its translocation into the gastrointestinal tract in rats after a single oral administration of an excessive dose (500 mg/kg) and observed changes in body weight, major organ weights, and organ tissue sections for periods of up to 2 weeks. The results indicated that GCS causes no deleterious effects. The results of an oral administration of rhodamine-labeled chitosan and an evaluation of its migration in the gastrointestinal tract suggested that the disappearance of rhodamine-labeled GCS from the body appeared to be slower than that of the non-dose group and pre-guanidinylated chitosan due to its mucoadhesive properties. In the future, we plan to investigate the use of GCS to improve absorption using Class III and IV drugs, which are poorly water-soluble as well as poorly membrane-permeable.

Alternate-day fasting induces metabolic and morphofunctional changes in the gastrointestinal tract of male rats.

Alternate-day fasting (ADF) is a nutritional intervention with modulatory and overall protective effects, but its role in the gastrointestinal (GI) tract is still uncertain. The aim of this study was to investigate the influence of ADF on the metabolic patterns and morphofunctional motility of the GI tract in rats. Thirty-two male Wistar rats were allocated into groups: control for 15 days (CON 15, n=8), control for 30 days (CON 30, n=8), ADF for 15 days (ADF 15, n=8), and ADF for 30 days (ADF 30, n=8). Blood glucose, body weight, and food and water consumption were measured. Frequency and amplitude of gastric contractions as well as gastric emptying time, small intestinal transit time, and cecum arrival time were measured. Intestinal histomorphometric, relative weight of organs, lipidogram, and leptin levels were also evaluated. ADF decreased water consumption and food consumption. The weight gain decreased; however, the relative kidney weight increased. ADF triggered an increase in the amplitude of gastric contractions and accelerated gastric emptying. However, small intestinal transit time was delayed in both ADF groups. Total cholesterol, triglycerides, non-HDL cholesterol, and very low-density lipoprotein cholesterol levels decreased, whereas villus height, depth of the crypts and thickness of the circular, and longitudinal muscular layers of intestine increased after ADF. In conclusion, our results showed ADF exert an effect on both metabolism and GI motility and impacts on overall digestive functions.

Inventarisasi Parasit Gastrointestinal Tikus (Rattus spp) di Pasar Oeba dan Pasar Inpres Naikoten Kota Kupang

Rats (Rattus spp) are known as pests as well as sources of zoonotic diseases such as bubonic plague, leptospirosis, bush fever, salmonellosis, inflammation of the brain, pneumonia, blood diarrhea, and gastritis caused by parasites. So, a study was conducted to see the types of endoparasites in the gastrointestinal tract of rats (Rattus spp) at the Inpres Naikoten Market and Oeba Market and to find out whether there are zoonotic parasites. The samples used were 50 digestive organs of rats (Rattus spp) and fresh feces. Identification was carried out using the nematode clearing method, at the dehydration stage using alcohol 30%, 50%, 96% and at the clearing stage using clove oil to purify adult worms. The simple flotation method was used to determine whether or not eggs of worms and protozoa were present in the feces of rats (Rattus spp). The results showed that adult Cestoda worms were found and no protozoa were found in the feces of rats (Rattus spp).

Leptin system is not affected by different diets in the abomasum of the sheep reared in semi-natural pastures of the Central Apennines

The growing summer drought stress is affecting the nutritional value of pastures, no longer sufficient to support the nutritional status of sheep in extensive rearing. Adipokines affect organ and tissue functionality can be useful to evaluate animal welfare and prompt an improvement in the management of the grazing animals. Leptin (Lep) is an adipokine mainly produced by adipose tissue that regulates food intake by an anorexigenic action. Lep has also been detected in the human and rat gastrointestinal tract, where it regulates the rate of gastric emptying. In this study, Lep system was evaluated in the abomasum of 15 adult sheep reared on Apennine pastures and subjected to different diets. Until the maximum pasture flowering (MxF group), the sheep fed on fresh forage; from that moment until the maximum pasture dryness (MxD group), the experimental group (Exp group) received a feed supplementation in addition to MxD group feeding. The Lep system was investigated in the abomasum samples by immunohistochemistry (IHC) and RT-qPCR. Double-label localisation of Lep and leptin receptor (LepR) with neuroendocrine hormones was conducted to distinguish the gland cell types. The analysis performed revealed the presence of Lep and LepR in the chief and neuroendocrine cells of the fundic glands of the abomasum. RT-qPCR evidenced the transcript for Lep and LepR also identifying the long isoform (LepRb). No significant differences were observed among the three groups of sheep subjected to different diets. The abundant immunostaining observed in the fundic glands suggests that the Lep intervenes in the regulation of abomasum in sheep with a similar pattern to monogastric species while long term food supplementation seems do not influence the local function of the Lep system. A better understanding of the gastrointestinal system can contribute to improving sheep management and optimising the sustainability of livestock production.

Micronucleus test using formalin-fixed rat glandular stomach and colon

BackgroundGenotoxicity in tissues other than hematopoietic tissues, such as the liver and gastrointestinal (GI) tract, is an important focus in the risk assessment of chemicals in humans. We previously developed a rat micronucleus test for the GI tract, which is the first contact tissue where chemicals are introduced into the body through oral exposure. Target cells were obtained from fresh tissue samples by ethylenediaminetetraacetic acid disodium salt (EDTA) treatment. As an improvement to this method, we have used formalin-fixed tissues instead of fresh tissues; this approach can be used for tissues that are sampled from other toxicological tests and that are archived for several years. This new method can be used for examining micronucleus induction retrospectively when needed. In the present study, we compared the performance of the EDTA method and the new method with formalin-fixed tissues (formalin-fixation method).ResultsHistological examination showed that both the EDTA and formalin-fixation methods could be used for collecting cells located in or above the proliferative zone of the GI tract tissues of rats. In addition, the collected cells were similar in shape. We conducted micronucleus tests with rat GI tract tissues by the two methods using model chemicals, which were used as positive control chemicals (a combination of diethylnitrosamine, 1,2-dimethylhydrazine dihydrochloride, and potassium bromate). The two methods showed similar results. We additionally evaluated the aging effect of tissues stored in formalin fixative. The results showed that 1 year of storage did not affect the frequency of micronucleated cells.ConclusionThe equivalence of the EDTA and formalin-fixation methods was confirmed, and micronucleus analysis was possible up to at least 1 year after formalin fixation of the GI tract, indicating that the formalin-fixation method is valuable for the rat GI tract micronucleus test.

Characterization of extracellular vesicles from Lactiplantibacillus plantarum

We investigated the characteristics and functionalities of extracellular vesicles (EVs) from Lactiplantibacillus plantarum (previously Lactobacillus plantarum) towards host immune cells. L. plantarum produces EVs that have a cytoplasmic membrane and contain cytoplasmic metabolites, membrane and cytoplasmic proteins, and small RNAs, but not bacterial cell wall components, namely, lipoteichoic acid and peptidoglycan. In the presence of L. plantarum EVs, Raw264 cells inducibly produced the pro-inflammatory cytokines IL-1β and IL-6, the anti-inflammatory cytokine IL-10, and IF-γ and IL-12, which are involved in the differentiation of naive T-helper cells into T-helper type 1 cells. IgA was produced by PP cells following the addition of EVs. Therefore, L. plantarum EVs activated innate and acquired immune responses. L. plantarum EVs are recognized by Toll-like receptor 2 (TLR2), which activates NF-κB, but not by other TLRs or NOD-like receptors. N-acylated peptides from lipoprotein19180 (Lp19180) in L. plantarum EVs were identified as novel TLR2 ligands. Therefore, L. plantarum induces an immunostimulation though the TLR2 recognition of the N-acylated amino acid moiety of Lp19180 in EVs. Additionally, we detected a large amount of EVs in the rat gastrointestinal tract for the first time, suggesting that EVs released by probiotics function as a modulator of intestinal immunity.

Effects of Energy Drink Acute Assumption in Gastrointestinal Tract of Rats.

Energy drinks (EDs) are non-alcoholic beverages containing high amounts of caffeine and other psychoactive substances. EDs also contain herbal extract whose concentration is usually unknown. EDs can have several adverse effects on different organs and systems, but their effects on the gastrointestinal (GI) tract have been poorly investigated. To determine the acute effects of EDs on the GI tract, we administered EDs, coffee, soda cola, or water to Sprague–Dawley rats (n = 7 per group, randomly assigned) for up to five days, and analyzed the histopathological changes in the GI tract. Data were compared among groups by Kruskal–Wallis or Mann–Whitney tests. We found that, while EDs did not cause any evident acute lesion to the GI tract, they triggered eosinophilic infiltration in the intestinal mucosa; treatment with caffeine alone at the same doses found in EDs leads to the same effects, suggesting that it is caffeine and not other substances present in the EDs that causes this infiltration. The interruption of caffeine administration leads to the complete resolution of eosinophilic infiltration. As no systemic changes in pro-inflammatory or immunomodulating molecules were observed, our data suggest that caffeine present in ED can cause a local, transient inflammatory status that recruits eosinophils.

Synthesis, Characteristics, and Pharmaceutical Properties of Ibuprofen-Cyclodextrin-PEG Conjugate

The NSAIDs ibuprofen was chemically conjugated to the PEG-graft-β-CyD with an ester bond and its aqueous solubility was clearly improved. The preliminary release profile of ibuprofen in rat gastrointestinal tract contents was performed at 37°C within 12 hours. The polymeric conjugate almost did not release ibuprofen in the contents of stomach, released ibuprofen only 7.4% in the contents of small intestine, and evidently released ibuprofen up to 58.7% in the contents of colon, respectively. These results demonstrated that the polymeric conjugate was site-specifically biodegraded in the rat colonic contents. On the other hand, the xylene-induced ear swelling technique, the hot plate test, and the brewer's yeast-induced hyperthermia model in mice were performed for evaluating the anti-inflammatory, analgesic, and antipyretic activities of the polymeric conjugate, respectively. The results revealed that the polymeric conjugate maintained a long and stable pharmacodynamic efficiency over a period of 24 hours. Hence, the present polymeric ibuprofen-cyclodextrin-PEG conjugate may be of value as an orally administered long-acting prodrug of ibuprofen through colon-targeting delivery.

Why is motilin active in some studies with mice, rats, and guinea pigs, but not in others? Implications for functional variability among rodents.

The gastrointestinal (GI) hormone motilin helps control human stomach movements during hunger and promotes hunger. Although widely present among mammals, it is generally accepted that in rodents the genes for motilin and/or its receptor have undergone pseudonymization, so exogenous motilin cannot function. However, several publications describe functions of low concentrations of motilin, usually within the GI tract and CNS of mice, rats, and guinea pigs. These animals were from institute‐held stocks, simply described with stock names (e.g., “Sprague–Dawley”) or were inbred strains. It is speculated that variation in source/type of animal introduces genetic variations to promote motilin‐sensitive pathways. Perhaps, in some populations, motilin receptors exist, or a different functionally‐active receptor has a good affinity for motilin (indicating evolutionary pressures to retain motilin functions). The ghrelin receptor has the closest sequence homology, yet in non‐rodents the receptors have a poor affinity for each other's cognate ligand. In rodents, ghrelin may substitute for certain GI functions of motilin, but no good evidence suggests rodent ghrelin receptors are highly responsive to motilin. It remains unknown if motilin has functional relationships with additional bioactive molecules formed from the ghrelin and motilin genes, or if a 5‐TM motilin receptor has influence in rodents (e.g., to dimerize with GPCRs and create different pharmacological profiles). Is the absence/presence of responses to motilin in rodents’ characteristic for systems undergoing gene pseudonymization? What are the consequences of rodent supplier‐dependent variations in motilin sensitivity (or other ligands for receptors undergoing pseudonymization) on gross physiological functions? These are important questions for understanding animal variation.

MORPHOFUNCTIONAL CHANGES IN GASTROINTESTINAL TRACT OF RATS DURING SULFUR MUSTARD INTOXICATION

Sulfur mustard (SM) is a highly toxic blistering agent (vesicant) that has been widely used as a chemical weapon in wars and armed conflicts. Not only highly effective antidotes, but also tools for pathogenetic therapy of SM-induced lesions currently are not available, which necessitates further research in this field. Aim of the study: to examine the morphofunctional changes in gastrointestinal tract of rats during SM intoxication. Materials and methods. In experiments on rats during SM intoxication the severity of diarrhoea, propulsive activity and the specific mass of gastrointestinal tract were assessed, as well as performed a pathomorphological study of the small intestine. Results of the study. The obtained data indicate the development of the combined motor-evacuation, barrier, secretory-absorption and digestive intestinal dysfunction during SM intoxication. Conclusions. According to the authors, syndrome of intestinal insufficient is an important component of patho- and thanatogenesis of SM intoxication. Moreover, fluid sequestration and endocavitary pressure increase in gastrointestinal tract, which develop in consequence of its functional inability, should be considered as additional pathogenetic components of intoxication.

Intraluminal Behavior of Various Transporter Substrates in the Rat Gastrointestinal Tract.

The aim of this study was to evaluate the intraluminal behavior of various transporter substrates in different regions of the gastrointestinal (GI) tract. Drug solutions containing non-absorbable FITC-dextran 4000 (FD-4), were orally administered to rats. Residual water was sampled from the GI regions to measure the luminal drug concentration. Cephalexin (CEX), a substrate of the proton-coupled oligopeptide transporter, was absorbed rapidly, and no drug was detected in the lower small intestine. Saquinavir (SQV) was primarily absorbed in the upper region. However, unlike CEX, SQV was detected even in the lower segment probably due to the efflux of SQV via P-glycoprotein (P-gp). The concentration of methotrexate (MTX) showed a similar pattern to that of non-absorbable FD-4. The low absorption of MTX was probably due to efflux via several efflux transporters, and the limited expression of proton-coupled folate transporter, an absorptive transporter for MTX, in the upper region. This study revealed that the luminal concentration pattern of each drug differed considerably depending on the site because of the different absorption properties and luminal volumes. Although further investigation using a specific transporter inhibitor or transporter-knockout animals are necessary to clarify the actual contribution of each transporter to the drug absorption, this information will be valuable in evaluating transporter-mediated drug absorption in in vitro transport studies for ensuring optimal drug concentrations.