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Purpose: We determined the effects of different environmental temperatures on exercise-induced gastrointestinal (GI) damage and delayed gastric emptying (GE) rate. Methods: Eleven trained males completed three trials on different days, consisting of (1) exercise in a thermoneutral environment (CON, 23 °C), (2) exercise in a hot environment (HOT, 35 °C), and (3) exercise in a cold environment (COLD, 10 °C). The subjects performed high-intensity interval-type endurance exercises in all trials. Blood intestinal fatty acid binding protein (I-FABP) levels was determine before and after exercise. We evaluated Tmax (time when the 13C-excretion/h reached a maximum level) as an indication of the GE rate during post-exercise. Results: Rectal temperature during exercise was significantly higher (P < 0.001) in the HOT (38.7 ± 0.3 °C) trial compared with the CON (38.2 ± 0.3 °C) and COLD (38.2 ± 0.3 °C) trials, with no significant difference between the CON and COLD trials. Plasma I-FABP level after exercise (relative to the pre-exercise level) were significantly greater (P = 0.005) in the HOT trial (92.9 ± 69.6%) than in the CON (37.2 ± 31.6%) and COLD (37.6 ± 41.8%) trials. However, there was no significant difference between the CON and COLD trials. Moreover, the Tmax was delayed significantly (P = 0.006) in the HOT trial compared with the CON and COLD trials, with no significant difference between the CON and COLD trials. Conclusion: GI function following endurance exercise was similar between thermoneutral and cold environments, while endurance exercise in a hot environment exacerbated GI function compared with thermoneutral and cold environments. [ABSTRACT FROM AUTHOR]

Irinotecan causes severe gastrointestinal damage, which may affect the expression of intestinal transporters. However, neither the expression of peptide transporter 1 (Pept1) nor the pharmacokinetics of Pept1 substrate drugs has been investigated under irinotecan‐induced gastrointestinal damage. Therefore, the present study quantitatively investigated the effects of irinotecan‐induced gastrointestinal damage on the intestinal expression of Pept1 and absorption of cephalexin (CEX), a typical Pept1 substrate, in rats. Irinotecan was administered intravenously to rats for 4 days to induce gastrointestinal damage. The expression of Pept1 mRNA and the Pept1 protein in the upper, middle, and lower segments of the small intestine of irinotecan‐treated rats was assessed by quantitative real‐time polymerase chain reaction (PCR) and western blotting, respectively. The pharmacokinetic profile of CEX was examined after its oral or intravenous administration (10 mg/kg). In irinotecan‐treated rats, ∼2‐fold increases in Pept1 protein levels were observed in all three segments, whereas mRNA levels remained unchanged. The oral bioavailability of CEX significantly decreased to 76% of that in control rats. The decrease in passive diffusion caused by intestinal damage may have overcome the increase in Pept1‐mediated uptake. In conclusion, irinotecan may decrease the intestinal absorption of Pept1 substrate drugs; however, it increased the expression of intestinal Pept1. [ABSTRACT FROM AUTHOR]

Gastrointestinal damage is generated by a wide range of harmful agents, and is the result of the activation of inflammatory, oxidant and cytotoxic mechanisms, that together overwhelm the “mucosa defense” of the gastrointestinal (GI) tract. It is currently known that the mechanisms by which gastric damage is generated are slightly different from those that generate intestinal damage. The treatments available on the market such as citoprotectors, the use of selective Ciclooxigenase 2 (COX-2) inhibitors, the co-prescription of acid suppressive agents and the use of prostaglandin analogues are mainly focused on the mechanisms of gastric damage, and their use has begun to be limited due to its adverse effects at intestinal and cardiovascular level. Due to its multifactorial origin, the prevention and treatment of GI damage requires effective therapies that can protect both gastric and intestinal level modulating more than one mechanism. Recently, has been reported the contribution of gaseous mediators nitric oxide (NO), hydrogen sulfide (H2S) and carbon monoxide (CO) in many physiological processes in the gastrointestinal tract, including the maintenance of GI mucosal barrier integrity. Experimental evidence has shown promising results regarding the gastric safety of these gasotransmitters, especially those coupled to NSAIDs. This review will try to give a general overview of the mechanisms of gastric and intestinal damage, their main differences, the existing therapies for their treatment and the information available on gas transmitters with a brief description of roles of each of these gaseous molecules.

This work aimed to evaluate the gastrointestinal and metabolic effect in a murine model of a snack rich in fiber (corn, chickpea, sesame, and chia) (HFS) and the comparison with the consumption of a commercial corn snack (CMS). Unlike the commercial snack, the mixture of corn, chickpea, sesame, and chia improved the nutritional quality of the final product. In the evaluation of the intake of the different diets in the mouse model, high-fiber snack (HFS) decreased cholesterol and triglyceride levels after 30 days of consumption, while CMS increased glucose levels and caused metaplasia in gastric tissue, in addition to decreasing the height villus in small intestinal tissue. The reformulation of snacks, using in addition to cereals, legumes, and oilseeds, can be a functional food easily accessible to the population, being a better option than snacks of low nutritional quality that are on the market. [ABSTRACT FROM AUTHOR]

To determine the effects of heat acclimation on gastrointestinal (GI) damage and the gastric emptying (GE) rate following endurance exercise in a hot environment. Fifteen healthy men were divided into two groups: endurance training in hot (HOT, 35 °C, n = 8) or cool (COOL, 18 °C, n = 7) environment. All subjects completed 10 days of endurance training (eight sessions of 60 min continuous exercise at 50% of the maximal oxygen uptake ( V · O 2 max ). Subjects completed a heat stress exercise tests (HST, 60 min exercise at 60% V · O 2 max ) to evaluate the plasma intestinal fatty acid-binding protein (I-FABP) level and the GE rate following endurance exercise in a hot environment (35 °C) before (pre-HST) and after (post-HST) the training period. We assessed the GE rate using the 13C-sodium acetate breath test. The core temperature during post-HST exercise decreased significantly in the HOT group compared to the pre-HST (p = 0.004) but not in the COOL group. Both the HOT and COOL groups showed exercise-induced plasma I-FABP elevations in the pre-HST (p = 0.002). Both groups had significantly attenuated exercise-induced I-FABP elevation in the post-HST. However, the reduction of exercise-induced I-FABP elevation was not different significantly between both groups. GE rate following HST did not change between pre- and post-HST in both groups, with no significant difference between two groups in the post-HST. Ten days of endurance training in a hot environment improved thermoregulation, whereas exercise-induced GI damage and delay of GE rate were not further attenuated compared with training in a cool environment. [ABSTRACT FROM AUTHOR]

Pelvic irradiation, a crucial treatment for pelvic malignancies, is associated with the risk of gastrointestinal (GI) damage due to the high proliferation rate of epithelial cells. The radiosensitive gastrointestinal tract acts as a dose-limiting organ. High doses of ionizing radiation can cause inflammation and rupture of mucosal barriers and can also lead to intestinal fibrosis. Intestinal damage can cause acute to chronic complications, reducing patients' quality of life. The gut microbiota plays a vital role in maintaining gut health, and any changes in the gut microbial composition can worsen damage, emphasizing the importance of therapies that target and sustain the gut microbiota during radiotherapy. One potential strategy to prevent radiation-induced GI damage is to use bacterial supplements. Research suggests that probiotic supplementation may alleviate radiation-induced gastrointestinal damage, maintaining intestinal morphology and decreasing epithelial injury in cancer patients. The observed protective effects occur through various mechanisms, including antioxidant activities, modulation of the immune response, and preservation of gut barrier function. To optimize probiotic therapies, it is imperative to elucidate these mechanisms. The efficiency of probiotics as radioprotectors is highly dependent on the time and dose of administration, and their interaction with the host immune system is a key facet of their therapeutic potential. This review explores the potential benefits of bacterial supplementation in mitigating radiation-induced GI damage and the underlying mechanism. This highlights the need for further research to establish standardized protocols and refine probiotic supplementation strategies, underscoring the potential for enhancing therapeutic outcomes in patients undergoing pelvic radiotherapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract Background Irinotecan (CPT-11) is clinically known to cause severe diarrhea and gastrointestinal damage. Recently, we have reported that CPT-11-induced gastrointestinal damage is associated with the upregulation of intestinal P-glycoprotein (P-gp) expression and decreased absorption of its substrate, dabigatran etexilate (DABE), using a rat model. However, the P-gp activity or its contribution to the decreased absorption remains unclear. The aim of this study was to quantitatively evaluate how P-gp activity changes in rats with CPT-11-induced gastrointestinal damage, as assessed by the absorption of digoxin (DGX), a typical P-gp substrate. Methods Male Sprague-Dawley rats were intravenously administered CPT-11 at a dose of 60 mg/kg/day for 4 days to induce gastrointestinal damage. Then, the rats were administered DGX orally (40 μg/kg), after some of them were orally administered clarithromycin (CAM; 10 mg/kg), a P-gp inhibitor. DGX (30 μg/kg) was administered intravenously to determine the bioavailability (BA). The rats’ DGX plasma concentration profiles were determined using LC-MS/MS. Results CPT-11 treatment decreased the maximum concentration (Cmax) and area under the plasma concentration-time curve (AUCpo) of DGX, which does not contradict to the DABE study. Although in the CPT-11-treated group the BA of DGX was significantly decreased to 40% of the control value, CAM did not affect the BA of DGX in the CPT-11-treated group. Conclusions Increased P-gp expression in rats with CPT-11-induced gastrointestinal damage is not necessarily associated with increased P-gp activity or contribution to the drug absorption in vivo. The decreased DGX absorption observed in this study might be attributable to other factors, such as a reduction in the absorptive surface area of the gastrointestinal tract.

To determine the effects of heat acclimation on gastrointestinal (GI) damage and the gastric emptying (GE) rate following endurance exercise in a hot environment. Fifteen healthy men were divided into two groups: endurance training in hot (HOT, 35 °C, n = 8) or cool (COOL, 18 °C, n = 7) environment. All subjects completed 10 days of endurance training (eight sessions of 60 min continuous exercise at 50% of the maximal oxygen uptake (V·O2max). Subjects completed a heat stress exercise tests (HST, 60 min exercise at 60% V·O2max) to evaluate the plasma intestinal fatty acid-binding protein (I-FABP) level and the GE rate following endurance exercise in a hot environment (35 °C) before (pre-HST) and after (post-HST) the training period. We assessed the GE rate using the 13C-sodium acetate breath test. The core temperature during post-HST exercise decreased significantly in the HOT group compared to the pre-HST (p = 0.004) but not in the COOL group. Both the HOT and COOL groups showed exercise-induced plasma I-FABP elevations in the pre-HST (p = 0.002). Both groups had significantly attenuated exercise-induced I-FABP elevation in the post-HST. However, the reduction of exercise-induced I-FABP elevation was not different significantly between both groups. GE rate following HST did not change between pre- and post-HST in both groups, with no significant difference between two groups in the post-HST. Ten days of endurance training in a hot environment improved thermoregulation, whereas exercise-induced GI damage and delay of GE rate were not further attenuated compared with training in a cool environment.

Background: Irinotecan (CPT-11) is clinically known to cause severe diarrhea and gastrointestinal damage. Recently, we have reported that CPT-11-induced gastrointestinal damage is associated with the upregulation of intestinal P-glycoprotein (P-gp) expression and decreased absorption of its substrate, dabigatran etexilate (DABE), using a rat model. However, the P-gp activity or its contribution to the decreased absorption remains unclear. The aim of this study was to quantitatively evaluate how P-gp activity changes in rats with CPT-11-induced gastrointestinal damage, as assessed by the absorption of digoxin (DGX), a typical P-gp substrate. Methods: Male Sprague-Dawley rats were intravenously administered CPT-11 at a dose of 60 mg/kg/day for 4 days to induce gastrointestinal damage. Then, the rats were administered DGX orally (40 μg/kg), after some of them were orally administered clarithromycin (CAM; 10 mg/kg), a P-gp inhibitor. DGX (30 μg/kg) was administered intravenously to determine the bioavailability (BA). The rats' DGX plasma concentration profiles were determined using LC-MS/MS. Results: CPT-11 treatment decreased the maximum concentration (Cmax) and area under the plasma concentration-time curve (AUCpo) of DGX, which does not contradict to the DABE study. Although in the CPT-11-treated group the BA of DGX was significantly decreased to 40% of the control value, CAM did not affect the BA of DGX in the CPT-11-treated group. Conclusions: Increased P-gp expression in rats with CPT-11-induced gastrointestinal damage is not necessarily associated with increased P-gp activity or contribution to the drug absorption in vivo. The decreased DGX absorption observed in this study might be attributable to other factors, such as a reduction in the absorptive surface area of the gastrointestinal tract. [ABSTRACT FROM AUTHOR]

Aspirin-related gastrointestinal damage is of growing concern. Aspirin use modulates the gut microbiota and associated metabolites, such as bile acids (BAs), but how this impacts intestinal homeostasis remains unclear. Herein, using clinical cohorts and aspirin-treated mice, we identified an intestinal microbe, Parabacteroides goldsteinii , whose growth is suppressed by aspirin. Mice supplemented with P. goldsteinii or its BA metabolite, 7-keto-lithocholic acid (7-keto-LCA), showed reduced aspirin-mediated damage of the intestinal niche and gut barrier, effects that were lost with a P. goldsteinii hdhA mutant unable to generate 7-keto-LCA. Specifically, 7-keto-LCA promotes repair of the intestinal epithelium by suppressing signaling by the intestinal BA receptor, farnesoid X receptor (FXR). 7-Keto-LCA was confirmed to be an FXR antagonist that facilitates Wnt signaling and thus self-renewal of intestinal stem cells. These results reveal the impact of oral aspirin on the gut microbiota and intestinal BA metabolism that in turn modulates gastrointestinal homeostasis. [Display omitted] • Aspirin users have marked gut microbiota dysbiosis, contributing to intestinal injury • P. goldsteinii , depleted by aspirin, alleviates aspirin-related gut barrier disruption • P. goldsteinii and its metabolite 7-keto-LCA maintain intestinal homeostasis • 7-Keto-LCA, an FXR antagonist, facilitates Wnt signaling and stem cell proliferation Li and Ding et al. identify an intestinal microbe, Parabacteroides goldsteinii , whose growth is suppressed by aspirin. They show that P. goldsteinii and its metabolite 7-keto-lithocholic acid promoted repair of aspirin-associated intestinal damage by suppressing the bile acid receptor FXR and maintaining Wnt signaling in intestinal stem cells. [ABSTRACT FROM AUTHOR]

Patulin (PAT) is a toxic fungal metabolite, and oxidative damage was proved to be its important toxicity mechanism. Selenium nanoparticles (SeNPs) were prepared by reducing sodium selenite with chitosan as a stabilizer and used for preventing PAT-induced liver, kidney and gastrointestinal damage. SeNPs have good dispersibility, in vitro antioxidant activity, and are much less cytotoxic than sodium selenite. Cell culture studies indicated that SeNPs can effectively alleviate PAT-induced excessive production of intracellular ROS, the decline of glutathione peroxidase activity, and the suppression of cell viability. Evaluation of serum biochemical parameters, histopathology, oxidative stress biomarkers and activities of antioxidant enzymes in a mouse model showed that pre-treatment with SeNPs (2 mg Se/kg body weight) could ameliorate PAT-induced oxidative damage to the liver and kidneys of mice, but PAT-induced gastrointestinal oxidative damage and barrier dysfunction were not recovered by SeNPs, possibly because the toxin doses suffered by the gastrointestinal as the first exposed tissues exceeded the regulatory capacity of SeNPs. These results suggested that a combination of other strategies may be required to completely block PAT toxicity.

Purpose: Coronavirus disease 2019 (COVID-19) tends to affect multiple organs and induce abnormal laboratory parameters. We designed this study to investigate the association between carcinoembryonic antigen (CEA) elevation and SARS-CoV-2 infection. Methods: We retrospectively analyzed 177 patients with confirmed SARS-CoV-2 infection who received plasma CEA assays during hospitalization. Patients with other causes of CEA elevation were excluded. Data regarding epidemiological and demographical characteristics, clinical symptoms, laboratory tests, and outcomes were analyzed. Linear regression analysis was used to evaluate the correlation between CEA levels and inflammation severity. Results: 171 patients were included in the final study and 32 patients (18.7%) had raised serum of CEA (> 5 ng/ml), with a median (range) age of 66 (53–86). The median [interquartile range (IQR)] CEA level was 11.4 ng/ml (8.1–21.6), which was significantly higher than the upper limit of reference range. CEA level between 5–10 ng/ml was in 11 patients, 10–15 ng/ml in 10 patients, and > 15 ng/ml in 11 patients. No correlation was found between CEA levels and lymphocyte (R2 = 0.055; P = 0.10) nor CRP (R2 = 0.026; P = 0.38). The median levels of CEA were 20.0 ng/ml (IQR, 14.7–23.0) in non-survivors and 10.9 ng/ml (IQR 7.5–16.1) in survivors, and the difference between two groups was statistically significant (P = 0.048). Conclusion: SARS-CoV-2 infection might be another cause of CEA elevation, with nearly 20% of patients experienced transient and marked CEA increment during COVID-19 pneumonia. The false-positive results of CEA elevation might have clinical significance for patients with colorectal cancer. [ABSTRACT FROM AUTHOR]

BACKGROUND: Capsaicin, as a major pungent ingredient of peppers, has many health benefits. However, the strong irritation effect of capsaicin inhibits its application in the food industry. Emulsions can be an effective approach to alleviate the irritation. RESULTS: In this study, we used tocopheryl polyethylene glycol 1000 succinate (TPGS) as an emulsifier to prepare capsaicin emulsions through high‐pressure homogenization. Capsaicin emulsions with a particle size of about 100 nm, −36.4 mV zeta potential, and 91.9% encapsulation efficiency were prepared successfully and showed better environmental stability and higher antioxidant activity. Emulsions reduced the cumulative release of capsaicin and had no toxic effect on buffalo rat liver (BRL‐3A) cells. Moreover, the gastrointestinal injury model of rats showed that emulsions reduced the strong irritation of capsaicin. CONCLUSION: This work provides a theoretical basis for the application of irritant ingredients in food industry. © 2019 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Irinotecan causes serious gastrointestinal damage. Dabigatran etexilate (DABE), an oral anticoagulant and substrate of P‐glycoprotein (P‐gp), is poorly absorbed and exhibits low bioavailability in humans. The aim of this study was to evaluate the effects of irinotecan‐induced gastrointestinal damage on the pharmacokinetics/pharmacodynamics (PK/PD) of DABE. Irinotecan was administered intravenously to rats for 4 days to induce gastrointestinal damage. To investigate the PK profile of dabigatran (DAB), an active moiety of DABE, DABE was administered orally on day 5, and then DAB was administered intravenously on day 6. To evaluate the PD profile of DAB, the activated partial thromboplastin time (APTT) was measured. The protein expression level of intestinal P‐gp was evaluated. In the irinotecan‐treated rats, the area under the concentration–time curve of DAB after the oral administration of DABE and the bioavailability of DABE were decreased significantly. The APTT ratio also decreased, suggesting that the impaired efficacy of DABE was attributable to a reduction in its bioavailability. The expression of intestinal P‐gp was higher in the irinotecan‐treated rats. Taking into consideration the histological damage caused to the intestinal epithelium, both the increased P‐gp expression and the reduced passive diffusion were considered to be responsible for the reduction in the bioavailability of DABE. [ABSTRACT FROM AUTHOR]

Indomethacin is a non-steroidal anti-inflammatory drug that causes gastric ulceration and increased 'leakiness' in rat models, and is used routinely as a toxicology assay to screen novel compounds for repair and restitution properties. We set out to establish conditions for indomethacin-induced gut damage in wax-moth (Galleria mellonella) larvae with a view to reducing the need for rodents in such experimentation. We administered indomethacin (0.5–7.5 µg/larva; 2–30 mg/kg) to G. mellonella via intrahaemocoelic injection and gavage (force-feeding) and monitored survival and development, blood cell (haemocyte) numbers, and changes in gut permeability. Increased levels of gut leakiness were observed within the first 4- to 24 h by tracking fluorescent microspheres in the faeces and haemolymph (blood equivalent). Additionally, we recorded varying levels of tissue damage in histological sections of the insect midgut, including epithelial sloughing and cell necrosis. Degeneration of the midgut was accompanied by significant increases in detoxification-associated activities (superoxide dismutase and glutathione-S-transferase). Herein, we present the first evidence that G. mellonella larvae force-fed indomethacin display broad symptoms of gastric damage similar to their rodent counterparts. [ABSTRACT FROM AUTHOR]

Purpose: Strenuous exercise induces intestinal injury, which is likely related to splanchnic hypoperfusion and may be associated with gastrointestinal complaints commonly reported during certain exercise modalities. Increasing circulating nitric oxide (NO) levels or inducing postprandial hyperemia may improve splanchnic perfusion, thereby attenuating intestinal injury during exercise. Therefore, we investigated the effects of both dietary nitrate ingestion and sucrose ingestion on splanchnic perfusion and intestinal injury induced by prolonged strenuous cycling. Methods: In a randomized crossover manner, 16 well-trained male athletes (age, 28 ± 7 yr; W max, 5.0 ± 0.3 W·kg−1) cycled 60 min at 70% W max after acute ingestion of sodium nitrate (NIT; 800 mg NO3), sucrose (SUC; 40 g), or a water placebo (PLA). Splanchnic perfusion was assessed by determining the gap between gastric and arterial pCO2 (gapg-apCO2) using gastric air tonometry. Plasma intestinal fatty acid–binding protein (I-FABP) concentrations, reflecting enterocyte damage, were assessed every 20 min during and up to 60 min of postexercise recovery. Results: The exercise protocol resulted in splanchnic hypoperfusion, as gapg-apCO2 levels increased during exercise (P < 0.001), with no differences between treatments (P = 0.47). Although plasma I-FABP concentrations increased during exercise and postexercise recovery for all treatments (P < 0.0001), the increase was different between treatments (P < 0.0001). Post hoc comparisons showed an attenuated increase in I-FABP in SUC versus PLA (P = 0.020). In accordance, I-FABP area under the curve (AUC0–120) was significantly lower in SUC versus PLA (57,270 ± 77,425 vs 114,907 ± 91,527 pg·mL−1 per 120 min, P = 0.002). No differences were observed between NIT and PLA (P = 0.99). Conclusion: Sucrose but not nitrate ingestion lowers intestinal injury evoked during prolonged strenuous cycling. These results suggest that sucrose ingestion, but not nitrate, prevents hypoperfusion-induced gastrointestinal damage during exercise and, as such, may help to lower exercise-related gastrointestinal complaints. [ABSTRACT FROM AUTHOR]

Abstract: Preclinical Research & Development The objective of the present study was to evaluate the tapentadol–diclofenac combination in three dose‐ratios in the mouse acetic acid‐induced visceral pain and their ulcerogenic activity on the stomachal mucous. Dose‐response curves were generated for tapentadol, diclofenac, and their combination in the acetic acid‐induced writhing test in mice. Moreover, the stomachs of animals were surgically removal and gastrointestinal ulcerogenic action of the combination was assessed. The isobolographic analysis, interaction index, and ANOVA were used to analyze the data. The isobolographic analysis and interaction index showed a similar antinociceptive activity for the three combinations of the analgesic mixture. Moreover, tapentadol and the proportions 1:1 or 3:1 of the analgesic combination caused a mild gastrointestinal damage. These data indicate that the systemic co‐administration of tapentadol and diclofenac produced a synergistic interaction in the acetic acid‐induced visceral pain test with an acceptable gastric damage profile in mice. [ABSTRACT FROM AUTHOR]

Cisplatin (CP) is a widely used chemotherapeutic agent that elicits severe gastrointestinal toxicity. Nigella sativa , a member of family Ranunculaceae, is one of the most revered medicinal plant known for its numerous health benefits. Thymoquinone (TQ), a major bioactive component derived from the volatile oil of Nigella sativa seeds, has been shown to improve gastrointestinal functions in animal models of acute gastric/intestinal injury. In view of this, the aim of the present study was to investigate the protective effect of TQ on CP induced toxicity in rat intestine and to elucidate the mechanism underlying these effects. Rats were divided into four groups viz. control, CP, TQ and CP + TQ. Animals in CP + TQ and TQ groups were orally administered TQ (1.5 mg/kg bwt) with and without a single intraperitoneal dose of CP (6 mg/kg bwt) respectively. The effect of TQ was determined on CP induced alterations in the activities of brush border membrane (BBM), carbohydrate metabolism, and antioxidant defense enzymes in rat intestine. TQ administration significantly mitigated CP induced decline in the specific activities of BBM marker enzymes, both in the mucosal homogenates and in the BBM vesicles (BBMV) prepared from intestinal mucosa. Furthermore, TQ administration restored the redox and metabolic status of intestinal mucosal tissue in CP treated rats. The biochemical results were supported by histopathological findings that showed extensive damage to intestine in CP treated rats and markedly preserved intestinal histoarchitecture in CP and TQ co-treated group. The biochemical and histological data suggest a protective effect of TQ against CP-induced gastrointestinal damage. Thus, TQ may have a potential for clinical application to counteract the accompanying gastrointestinal toxicity in CP chemotherapy. [ABSTRACT FROM AUTHOR]

Red seaweeds synthesize a great variety of sulfated galactans. Sulfated polysaccharides (PLSs) from seaweed are comprised of substances with pharmaceutical and biomedical potential. The aim of the present study was to evaluate the protective effect of the PLS fraction extracted from the seaweed Gracilaria birdiae in rats with naproxen-induced gastrointestinal damage. Male Wistar rats were pretreated with 0.5% carboxymethylcellulose (control group—vehicle) or PLS (10, 30, and 90 mg/kg, p.o.) twice daily (at 09:00 and 21:00) for 2 days. After 1 h, naproxen (80 mg/kg, p.o.) was administered. The rats were killed on day two, 4 h after naproxen treatment. The stomachs were promptly excised, opened along the greater curvature, and measured using digital calipers. Furthermore, the guts of the animals were removed, and a 5-cm portion of the small intestine (jejunum and ileum) was used for the evaluation of macroscopic scores. Samples of the stomach and the small intestine were used for histological evaluation, morphometric analysis and in assays for glutathione (GSH) levels, malonyldialdehyde (MDA) concentration, and myeloperoxidase (MPO) activity. PLS treatment reduced the macroscopic and microscopic naproxen-induced gastrointestinal damage in a dose-dependent manner. Our results suggest that the PLS fraction has a protective effect against gastrointestinal damage through mechanisms that involve the inhibition of inflammatory cell infiltration and lipid peroxidation.

Nonsteroidal anti-inflammatory drugs (NSAIDs), which are globally prescribed, exhibit mainly anti-inflammatory and analgesic effects but also can cause adverse effects including gastrointestinal erosions, ulceration, bleeding, and perforation. The purpose of this study was to investigate surrogate biomarkers associated with the gastrointestinal (GI) damage caused by NSAID treatment using pattern recognition analysis of 1 H-nuclear magnetic resonance ( 1 H NMR) spectra of rat urine. Urine was collected for 5 h after oral administration of the following NSAIDs at low or high doses: acetylsalicylic acid (10 or 200 mg kg −1 ), diclofenac (0.5 or 15 mg kg −1 ), piroxicam (1 or 10 mg kg −1 ), indomethacin (1 or 25 mg kg −1 ), or ibuprofen (10, or 150 mg kg −1 ) as nonselective COX inhibitors and celecoxib (10 or 100 mg kg −1 ) as a COX-2 selective inhibitor. The urine was analyzed using 500 MHz 1 H NMR for spectral binning and targeted profiling and the level of gastric damage was examined. The nonselective COX inhibitors caused severe gastric damage while no lesions were observed in the celecoxib-treated rats. The 1 H NMR urine spectra were divided into spectral bins (0.04 ppm) for global profiling, and a total of 44 endogenous metabolites were assigned for targeted profiling. Multivariate data analyses were performed to recognize the spectral pattern of endogenous metabolites related to NSAIDs using partial least square-discrimination analysis (PLS-DA). The 1 H NMR spectra clustered differently according to gastric damage score in global profiling. In targeted profiling, the endogenous metabolites of citrate, allantoin, 2-oxoglutarate, acetate, benzoate, glycine, and trimethylamine N-oxide were selected as putative biomarkers for gastric damage caused by NSAIDs. These putative biomarkers might be useful for predicting the risk of adverse effects caused by NSAIDs in the early stage of drug development process. [ABSTRACT FROM AUTHOR]

The choice of a specific medication belonging to a drug class is under the criteria of efficacy, safety, cost and suitability. NSAIDs currently constitute one of the most consumed drug in the world, so it is very important review of the safety aspects of this drug class. This review has the objective of analyze the safety of NSAIDs on 3 main criteria: gastrolesivity, cardiotoxicity and nephrotoxicity. [ABSTRACT FROM AUTHOR]

Purpose: Splanchnic hypoperfusion is a physiological phenomenon during strenuous exercise. It has been associated with gastrointestinal symptoms and intestinal injury and may hamper athletic performance. We hypothesized that L-citrulline supplementation improves splanchnic perfusion and decreases intestinal injury by enhancing arginine availability. The aim of this study was to determine the effect of L-citrulline intake on splanchnic perfusion, intestinal injury, and barrier function during exercise. Methods: In this randomized, double-blind crossover study, 10 men cycled for 60 min at 70% of their maximum workload after L-citrulline (10 g) or placebo (L-alanine) intake. Splanchnic perfusion was assessed using gastric air tonometry. Sublingual microcirculation was evaluated by sidestream dark field imaging. Plasma amino acid levels and intestinal fatty acid binding protein concentrations, reflecting enterocyte damage, were assessed every 10 min. Urinary excretion of sugar probes was measured to evaluate intestinal permeability changes. Results: Oral L-citrulline supplementation enhanced plasma citrulline (1840.3 ± 142.3 µM) and arginine levels (238.5 ± 9.1 µM) compared with that in placebo (45.7 ± 4.8 µM and 101.5 + 6.1 µM, respectively, P < 0.0001), resulting in increased arginine availability. Splanchnic hypoperfusion was prevented during exercise after L-citrulline ingestion (reflected by unaltered gapg-apCO2 levels), whereas gapg-apCO2 increased with placebo treatment (P < 0.01). Accordingly, L-citrulline intake resulted in an increased number of perfused small sublingual vessels compared with that in placebo (7.8 ± 6.0 vs —2.0 ± 2.4, P = 0.06). Furthermore, plasma intestinal fatty acid binding protein levels were attenuated during exercise after L-citrulline supplementation compared with that in placebo (AUC0-60 min, 185% ± 506% vs 1318% ± 553%, P < 0.01). No significant differences were observed for intestinal permeability. Conclusions: Pre-exercise L-citrulline intake preserves splanchnic perfusion and attenuates intestinal injury during exercise in athletes compared with placebo, probably by enhancing arginine availability. These results suggest that oral L-citrulline supplementation is a promising intervention to combat splanchnic hypoperfusion-induced intestinal compromise. [ABSTRACT FROM AUTHOR]

Patulin (PAT) is a toxic fungal metabolite, and oxidative damage was proved to be its important toxicity mechanism. Selenium nanoparticles (SeNPs) were prepared by reducing sodium selenite with chitosan as a stabilizer and used for preventing PAT-induced liver, kidney and gastrointestinal damage. SeNPs have good dispersibility, in vitro antioxidant activity, and are much less cytotoxic than sodium selenite. Cell culture studies indicated that SeNPs can effectively alleviate PAT-induced excessive production of intracellular ROS, the decline of glutathione peroxidase activity, and the suppression of cell viability. Evaluation of serum biochemical parameters, histopathology, oxidative stress biomarkers and activities of antioxidant enzymes in a mouse model showed that pre-treatment with SeNPs (2 mg Se/kg body weight) could ameliorate PAT-induced oxidative damage to the liver and kidneys of mice, but PAT-induced gastrointestinal oxidative damage and barrier dysfunction were not recovered by SeNPs, possibly because the toxin doses suffered by the gastrointestinal as the first exposed tissues exceeded the regulatory capacity of SeNPs. These results suggested that a combination of other strategies may be required to completely block PAT toxicity. [ABSTRACT FROM AUTHOR]

Calcium hydroxide is a strong alkali which may cause irreversible injury to tissues that comes in contact with this substance. It is commonly consumed as "choona" in paan or betel leaf preparations in this part of the world. We present a rare case of death due to overdose of calcium hydroxide consumed for a strange belief of being a slimming agent. The corrosive effects of calcium hydroxide caused severe bleeding from the upper GI tract and proved to be fatal. The social myths and ignorance with respect to such toxic compounds are resulting in morbidity and mortality even in this age. Here we have discussed the incidence, symptomatology, pathology and manner of calcium hydroxide poisoning. [ABSTRACT FROM AUTHOR]

Low-dose aspirin and thienopyridine are associated with gastrointestinal (GI) complications such as petechiae, erosion, ulcer, bleeding, and perforation. The incidence of GI bleeding in aspirin study groups was 0.82 % in the hypertension optimal treatment (HOT) study and 0.76 % in the primary prevention project (PPP) study. On the other hand, the incidence of GI bleeding by endoscopic evaluation was higher than in an observational study. In a study of 187 patients receiving low-dose aspirin for prevention of cardiovascular disease, the prevalence of endoscopically detected GI ulcers was 11 % (95 % CI 6.3-15.1 %). Several risk factors for GI bleeding (history of peptic ulcer or GI bleeding, high aspirin dose, concomitant use of non-steroidal anti-inflammatory drugs and anti-platelet agents, advanced age and Helicobacter pylori infection) were reported for patients receiving aspirin. Prevention strategies for GI complications induced by anti-platelet agents are treatment with proton pump inhibitors, histamine-2 receptor antagonists, prostaglandin analogs, prostaglandin inducers and H. pylori eradication therapy. Further investigation is necessary to identify the strategies which are suitable for Japan. [ABSTRACT FROM AUTHOR]

Gastrointestinal (GIT) diseases represent an important part of pediatric health disorders. The recent years have brought not only significant improvement of digestive endoscopy technologies and a new equipment suitable for pediatric age but also progress in management of diagnostic approach and treatment of the pediatric GIT diseases. In contrast to adult patients, endoscopic examination in pediatrics is in most cases performed for diagnostic, not therapeutical purposes. The histological assessment of biopsy specimens taken during endoscopy therefore forms an integral part of the endoscopic examination and in most cases the diagnosis cannot be concluded without their evaluation. In particular, the clinical gastroenterologist expects from the pathologist a description that will help confirm or contradict the diagnosis considered after the macroscopic examination. In this review, we would like to highlight the most common endoscopic findings of the gastrointestinal tract in pediatric population and the role of histology in determining the correct diagnosis.

The article discusses research which was conducted to determine the effect of oral ibuprofen administration before exercise on gastrointestinal (GI) integrity and barrier function in healthy individuals. Researchers evaluated plasma intestinal fatty acid binding protein (1-FABP) levels in nine men who either took 400 milligrams of ibuprofen twice before cycling, cycled without ibuprofen, took 400 milligrams of ibuprofen twice at rest, or were at rest without ibuprofen intake. They found that both ibuprofen consumption and cycling resulted in increased 1-FABP levels, reflecting small intestinal injury and that the levels were higher after cycling with ibuprofen than after cycling without ibuprofen, rest with ibuprofen, or rest without ibuprofen.

Red seaweeds synthesize a great variety of sulfated galactans. Sulfated polysaccharides (PLSs) from seaweed are comprised of substances with pharmaceutical and biomedical potential. The aim of the present study was to evaluate the protective effect of the PLS fraction extracted from the seaweed Gracilaria birdiae in rats with naproxen-induced gastrointestinal damage. Male Wistar rats were pretreated with 0.5% carboxymethylcellulose (control group--vehicle) or PLS (10, 30, and 90 mg/kg, p.o.) twice daily (at 09:00 and 21:00) for 2 days. After 1 h, naproxen (80 mg/kg, p.o.) was administered. The rats were killed on day two, 4 h after naproxen treatment. The stomachs were promptly excised, opened along the greater curvature, and measured using digital calipers. Furthermore, the guts of the animals were removed, and a 5-cm portion of the small intestine (jejunum and ileum) was used for the evaluation of macroscopic scores. Samples of the stomach and the small intestine were used for histological evaluation, morphometric analysis and in assays for glutathione (GSH) levels, malonyldialdehyde (MDA) concentration, and myeloperoxidase (MPO) activity. PLS treatment reduced the macroscopic and microscopic naproxen-induced gastrointestinal damage in a dose-dependent manner. Our results suggest that the PLS fraction has a protective effect against gastrointestinal damage through mechanisms that involve the inhibition of inflammatory cell infiltration and lipid peroxidation. [ABSTRACT FROM AUTHOR]

Abstract: The dose-dependent perturbations in urinary metabolite concentrations caused by naproxen toxicity were investigated using 1H NMR spectroscopy coupled with multivariate statistical analysis. Histopathologic evaluation of naproxen-induced acute gastrointestinal damage in rats demonstrated a significant dose-dependent effect. Furthermore, principal component analysis (PCA) of 1H NMR from rat urine revealed a dose-dependent metabolic shift between the vehicle-treated control rats and rats treated with low-dose (10mg/kg body weight), moderate-dose (50mg/kg), and high-dose (100mg/kg) naproxen, coinciding with their gastric damage scores after naproxen administration. The resultant metabolic profiles demonstrate that the naproxen-induced gastric damage exhibited energy metabolism perturbations that elevated their urinary levels of citrate, cis–aconitate, creatine, and creatine phosphate. In addition, naproxen administration decreased choline level and increased betaine level, indicating that it depleted the main protective constituent of the gastric mucosa. Moreover, naproxen stimulated the decomposition of tryptophan into kynurenate, which inhibits fibroblast growth factor-1 and delays ulcer healing. These findings demonstrate that 1H NMR-based urinary metabolic profiling can facilitate noninvasive and rapid diagnosis of drug side effects and is suitable for elucidating possible biological pathways perturbed by drug toxicity. [Copyright &y& Elsevier]

Abstract: Gastrointestinal toxicity remains a significant and dose-limiting complication of cancer treatment. While the pathophysiology is becoming clearer, considerable gaps in the knowledge remain surrounding the timing and site-specific gene changes which occur in response to insult. As such, this study aimed to assess gene expression profiles in a number of regions along the gastrointestinal tract following treatment with the chemotherapy agent, irinotecan, and correlate them with markers of cell death and tissue damage. Data analysis of microarray results found that genes involved in apoptosis, mitogen activated kinase (MAPK) signalling and inflammation were upregulated within 6h, while genes involved in cell proliferation, wound healing and blood vessel formation were upregulated at later time points up to 72h. Cell death was significantly increased at 6 and 24h, and the stomach showed the lowest severity of overt tissue damage. Real time PCR of MAPK signalling pathway genes found that the jejunum and colon had significantly increased expression in a number of genes at 72h, where as the stomach was unchanged. These results indicate that overall severity of tissue damage may be determined by precisely timed target gene responses specific to each region. Therapeutic targeting of key gene responses at the appropriate time point may prove to be effective for prevention of chemotherapy-induced gastrointestinal damage. [Copyright &y& Elsevier]

Drug use increases with age and the elderly is at increased risk of adverse drug reactions. Gastrointestinal adverse effects are one of the most often reported. Serious event are mostly caused by NSAIDs and/or aspirin which are the most widely prescribed medications in the world. NSAIDs and/or aspirin use are associated with complications from both the upper and the lower gastrointestinal tract. The risk of these complications depends on presence of risk factors, and age is the most frequent and relevant one. At-risk patients should be on prevention strategies including the use of the lowest effective dose, co-therapy with a gastroprotective agents or use of a COX-2 selective agent. Treatment of Helicobacter pylori infection is beneficial in patients starting therapy with these agents, especially in the presence of ulcer history. The best strategy to prevent lower GI complications has yet to be defined. [Copyright &y& Elsevier]

It is increasingly recognized that in children swallowed multiple magnets cause considerable damage to the gastrointestinal tract. To emphasize that complications from swallowed magnets are extensive worldwide and throughout childhood. The author surveyed radiologists and researched cases of magnet swallowing in the literature and documented age and gender, numbers of magnets, nature of the magnets, reasons for swallowing, and clinical course. A total of 128 instances of magnet swallowing were identified, one fatal. Cases from 21 countries were found. Magnet swallowing occurred throughout childhood, with most children older than 3 years of age. Numbers of swallowed magnets ranged up to 100. Twelve children were known to be autistic. Many reasons were given for swallowing magnets, and a wide range of gastrointestinal damage was encountered. Considerable delay before seeking medical assistance was frequent, as was delay before obtaining radiographs or US imaging. Damage from swallowing multiple magnets is a considerable worldwide problem. More educational and preventative measures are needed. [ABSTRACT FROM AUTHOR]

The side effects of NSAIDs are equally evident in the stomach and the small bowel. The latter is increasingly seen as being clinically significant, contributing substantially to the iron-deficiency anaemia that is so common in patients with rheumatoid arthritis. Furthermore, NSAID-enteropathy may be associated with life-threatening events. The pathogenesis of NSAID-enteropathy is uncertain but inhibition of COX-1 is believed to be of pivotal importance. However there is increasing evidence that COX-2 inhibition and the topical effect may have a synergistic detrimental action. We examined the role of COX-1, COX-2 and the so called topical effect of acidic NSAIDs. We found that COX-1 or COX-2 inhibition and the topical effect alone do not damage the GI tract. Dual inhibition of COX-1 and COX-2 results in intestinal inflammation similar to that caused by Indomethacin. The topical effect may act synergistically in this damage. The conventional view that the mechanism of gastrointestinal damage is principally caused by COX-1 inhibition needs to be revised in view of recent studies using selective inhibitors of the COX enzymes and COX knockout animals. [ABSTRACT FROM AUTHOR]

Pre-clinical studies suggest that, whilst NSAIDs have similar anti-inflammatory efficacy, the potential for producing side effects varies widely between members of this class of therapeutic agents. The ways in which NSAIDs produce one of their most serious side effects, gastrointestinal damage, are outlined and consideration is given to ways of minimizing such problems. [ABSTRACT FROM PUBLISHER]