Radiographic and histopathological study of gastrointestinal dysmotility in lipopolysaccharide-induced sepsis in the rat

AbstractSepsis is a highly incident condition in which a cascade of proinflammatory cytokines is involved. One of its most frequent consequences is ileus, which can increase mortality. Animal models such as that induced by systemic administration of lipopolysaccharide (LPS) are useful to deeply evaluate this condition. The effects of sepsis on the gastrointestinal (GI) tract have been explored but, to our knowledge, in vivo studies showing the motor and histopathological consequences of endotoxemia in an integrated way are lacking. Our aim was to study in rats the effects of sepsis on GI motility, using radiographic methods, and to assess histological damage in several organs.MethodsMale rats were intraperitoneally injected with saline or E. coli LPS at 0.1, 1, or 5 mg kg−1. Barium sulfate was intragastrically administered, and X‐rays were performed 0–24 h afterwards. Several organs were collected for organography, histopathology, and immunohistochemistry studies.Key ResultsAll LPS doses caused gastroparesia, whereas changes in intestinal motility were dose‐and time‐dependent, with an initial phase of hypermotility followed by paralytic ileus. Lung, liver, stomach, ileum, and colon (but not spleen or kidneys) were damaged, and density of neutrophils and activated M2 macrophages and expression of cyclooxygenase 2 were increased in the colon 24 h after LPS 5 mg kg−1.Conclusions and InferencesUsing radiographic, noninvasive methods for the first time, we show that systemic LPS causes dose‐, time‐, and organ‐dependent GI motor effects. Sepsis‐induced GI dysmotility is a complex condition whose management needs to take its time‐dependent changes into account

Contractility of isolated colonic smooth muscle strips from rats treated with cancer chemotherapy: differential effects of cisplatin and vincristine

BackgroundCertain antineoplastic drugs cause gastrointestinal disorders even after the end of treatment. Enteric neuropathy has been associated with some of these alterations. Our goal was to assess the impact of repeated treatment with cisplatin and vincristine on the contractility of circular and longitudinal muscle strips isolated from the rat colon.MethodsTwo cohorts of male rats were used: in cohort 1, rats received one intraperitoneal (ip) injection of saline or cisplatin (2 mg kg–1 week–1) on the first day of weeks 1–5; in cohort 2, rats received two cycles of five daily ip injections (Monday to Friday, weeks 1–2) of saline or vincristine (0.1 mg kg–1 day–1). Body weight and food and water intake were monitored throughout the study. One week after treatment, responses of colonic smooth muscle strips to acetylcholine (10–9–10–5 M) and electrical field stimulation (EFS, 0.1–20 Hz), before and after atropine (10–6 M), were evaluated in an organ bath.ResultsBoth drugs decreased body weight gain. Compared to saline, cisplatin significantly decreased responses of both longitudinal and circular smooth muscle strips to EFS, whereas vincristine tended to increase them, although in a non-significant manner. No differences were observed in the muscle response to acetylcholine. Atropine abolished the contractile responses induced by acetylcholine, although those induced by EFS were only partially reduced in the presence of atropine.ConclusionThe findings suggest that although both drugs cause the development of enteric neuropathy, this seems to have a functional impact only in cisplatin-treated animals. Understanding the effects of chemotherapy on gastrointestinal motor function is vital for enhancing the quality of life of cancer patients

Effects of vincristine and monosodium glutamate on gastrointestinal motility and visceral sensitivity

Background Chemotherapy‐induced adverse effects are an unresolved nightmare. In preclinical studies in rats, the food additive monosodium glutamate (MSG) improved some of the side effects caused by cisplatin, but its effects in other models of chemotherapy‐treated animals are not well known. The aim of this study was to test if MSG may improve some of the adverse effects induced by vincristine in rats. Methods Young male Wistar rats were exposed or not to MSG (4 g L−1) in drinking water from week 0 till 1 week after treatment (week 3). Rats received two cycles of five daily intraperitoneal (ip) injections (Monday to Friday, weeks 1 and 2) of either saline (2 mL kg−1) or vincristine (0.1 mg kg−1). Gastrointestinal motility was measured in vivo by radiological methods after the first and tenth ip administrations. On week 3, the threshold for mechanical somatic and colorectal sensitivity was recorded using Von Frey filaments applied to the paws and an intracolonic balloon, respectively. Finally, samples of the terminal ileum and distal colon were histologically evaluated in sections. Key Results Vincristine reduced body weight gain, food intake, and upper gastrointestinal transit, caused somatic (but not visceral) hypersensitivity and increased the thickness of the submucosal and muscle layers of the small intestine. In vincristine‐treated animals, MSG partially prevented gastrointestinal dysmotility and reduced visceral sensitivity but did not improve structural alterations of the small intestine. Conclusions and Inferences MSG could be used as an adjuvant to conventional treatments to improve some gastrointestinal dysfunctions caused by chemotherapy

Changes in fatty acid dietary profile affect the brain–gut axis functions of healthy young adult rats in a sex-dependent manner

This article belongs to the Special Issue Dietary Management of Gastrointestinal Diseases and Disorders.Dietary modifications, including those affecting dietary fat and its fatty acid (FA) composition, may be involved in the development of brain–gut axis disorders, with different manifestations in males and females. Our aim was to evaluate the impact of three purified diets with different FA composition on the brain–gut axis in rats of both sexes. Male and female Wistar rats fed a cereal-based standard diet from weaning were used. At young adult age (2–3 months old), animals were divided into three groups and treated each with a different refined diet for 6 weeks: a control group fed on AIN-93G diet containing 7% soy oil (SOY), and two groups fed on AIN-93G modified diets with 3.5% soy oil replaced by 3.5% coconut oil (COCO) or 3.5% evening primrose oil (EP). Different brain–gut axis parameters were evaluated during 4–6 weeks of dietary intervention. Compared with SOY diet (14% saturated FAs, and 58% polyunsaturated FAs), COCO diet (52.2% saturated FAs and 30% polyunsaturated FAs) produced no changes in brain functions and minor gastrointestinal modifications, whereas EP diet (11.1% saturated FAs and 70.56% polyunsaturated FAs) tended to decrease self-care behavior and colonic propulsion in males, and significantly increased exploratory behavior, accelerated gastrointestinal transit, and decreased cecum and fecal pellet density in females. Changes in FA composition, particularly an increase in ω-6 polyunsaturated FAs, seem to facilitate the development of brain–gut axis alterations in a sex-dependent manner, with a relatively higher risk in females.We thank Comunidad Autónoma de Madrid for the technician contract of Lorena Blanco (PEJ15/BIO/TL-0580) and the predoctoral contract of Yolanda López-Tofiño (PEJD-2017-PRE/BMD-3924), and URJC for the predoctoral contracts of Yolanda López-Tofiño and Carlos Gálvez-Robleño (both under PREDOC20-054 call). Damian Jacenik was a recipient of fellowship funded by Faculty of Biology and Environmental Protection, University of Lodz, Poland.Peer reviewe

Dependency on sex and stimulus quality of nociceptive behavior in a conscious visceral pain rat model

Visceral pain may be influenced by many factors. The aim of this study was to analyze the impact of sex and quality of intracolonic mechanical stimulus on the behavioral manifestations of visceral pain in a preclinical model. Male and female young adult Wistar rats were sedated, and a 5 cm long latex balloon was inserted into the colon. Sedation was reverted and behavior was recorded. The pressure of the intracolonic balloon was gradually increased using a sphygmomanometer. Visceral sensitivity was measured as abdominal contractions in response to mechanical intracolonic stimulation. Two different types of stimulation were used: tonic and phasic. Phasic stimulation consisted of repeating several times (3x) the same short stimulus (20 s) within a 5 min interval allowing a 1 min break between individual stimuli. For tonic stimulation the stimulus was maintained throughout the whole 5 min interval. Both phasic and tonic stimulation produced a pressure-dependent increase of abdominal contractions. The abdominal response was more intense under phasic than under tonic stimulation, but with differences depending on the sex of the animals: females exhibited more contractions than males and of similar duration at all pressures, whereas duration of contractions pressure-dependently increased in males. The duration of tonically stimulated contractions was lower and not sex- or pressure-dependent. In the rat, responses to colonic distension depend on the quality of the stimulus, which also produces sex-dependent differences that must be taken into account in the development of models of pathology and visceral pain treatments.Ministerio de Ciencia, Innovación y Universidades, Spain (PID2019- 111510RB-I00) and Grupo Español de Motilidad Digestiva, Spain(Beca Allergan, 2017)

Evaluation of the Effects of Instant Cascara Beverage on the Brain-Gut Axis of Healthy Male and Female Rats

Instant cascara (IC) is a sustainable beverage obtained from dried coffee cherry pulp, rich in nutrients and bioactive compounds. The present research aimed to determine the effects of IC on general health and brain-gut axis parameters of healthy female and male rats. Wistar rats were exposed to IC (10 mg/mL) in their drinking water for 3 weeks. Body weight and solid and liquid intakes were monitored as indicators of food safety. Gastrointestinal transit was radiographically evaluated one day (acute) and 3 weeks (chronic) after the start of IC exposure. Locomotor activity, anxiety, and anhedonia of the animals after 3 weeks of treatment was also studied. Overall, compared to water-exposed animals, IC significantly increased food intake in males (p < 0.0001) and liquid intake in females (p < 0.05) without changes in body weight in either case. IC did not significantly modify gastrointestinal motility parameters after its acute or repeated intake and did not cause any significant behavioral alterations in males or females (p > 0.05). In conclusion, repeated intake of IC at the studied concentration did not negatively affect brain-gut axis functions of healthy male and female rats. Anxiety behavior, diarrhea, constipation, abnormal weight modifications, or other typical effects of toxicity were not observed in animals treated with the new powdered beverage, suggesting its food safety under the studied conditions

Supplementary Material: Evaluation of the effects of instant cascara beverage on the brain-gut axis of healthy male and female rats

Figure S1: Effect of INSTANT CASCARA (IC) beverage on gastrointestinal transit of male and female rats evaluated radiographically 24 h after initiation of IC exposure (cohort 2). Figure S2: Effect of INSTANT CASCARA (IC) beverage on the morphometric and densitometric radiographic analysis of gastrointestinal organs 24 h after IC administration (cohort 2). Figure S3: Effect of INSTANT CASCARA (IC) beverage on the wet and dry weight of the feces of male and female rats. Feces were collected from the cages throughout the X-ray session (cohorts 1 and 2). Table S1: Effect of INSTANT CASCARA (IC) beverage on the macroscopic characteristics of the gastrointestinal organs and epididymal/periovarian and retroperitoneal fat at sacrifice. Table S2: Distribution of female animals (%) according to their estrous cycle in the different studies performed.Peer reviewe

Sars-Cov-2 Infection in Patients on Long-Term Treatment with Macrolides in Spain: A National Cross-Sectional Study

The aim of this study was to know the prevalence and severity of COVID-19 in patients treated with long-term macrolides and to describe the factors associated with worse outcomes. A cross-sectional study was conducted in Primary Care setting. Patients with macrolides dispensed continuously from 1 October 2019 to 31 March 2020, were considered. Main outcome: diagnosis of coronavirus disease-19 (COVID-19). Secondary outcomes: symptoms, severity, characteristics of patients, comorbidities, concomitant treatments. A total of 3057 patients met the inclusion criteria. Median age: 73 (64–81) years; 55% were men; 62% smokers/ex-smokers; 56% obese/overweight. Overall, 95% of patients had chronic respiratory diseases and four comorbidities as a median. Prevalence of COVID-19: 4.8%. This was in accordance with official data during the first wave of the pandemic. The most common symptoms were respiratory: shortness of breath, cough, and pneumonia. Additionally, 53% percent of patients had mild/moderate symptoms, 28% required hospital admission, and 19% died with COVID-19. The percentage of patients hospitalized and deaths were 2.6 and 5.8 times higher, respectively, in the COVID-19 group (p < 0.001). There was no evidence of a beneficial effect of long-term courses of macrolides in preventing SARS-CoV-2 infection or the progression to worse outcomes in old patients with underlying chronic respiratory diseases and a high burden of comorbidity