Administration Of Indomethacin Research Articles

Apigenin attenuates indomethacin-induced gastric ulcer in rats: emphasis on antioxidant, anti-inflammatory, anti-apoptotic, and TGF-β1 enhancing activities.

Gastric ulcer disease is associated with significant morbidity and mortality rates. The most two common causes of the ulcer are Helicobacter pylori infection and non-steroidal anti-inflammatory drugs. In the past few decades, a significant decrease in the morbidity and mortality rate has been observed probably due to the discovery of proton pump inhibitors. However, the medications used to treat gastric ulcers impose several nauseous side effects. Therefore, recent studies focus on the use of natural products to treat gastric ulcers. In the current study, gastric ulcer was effectively induced using indomethacin, and the protective effect of apigenin, a potent antioxidant flavonoid, was assessed in comparison to omeprazole. The administration of a single oral indomethacin (50mg/kg) induced gastric ulcer as manifested by hemorrhagic lesions in the gastric mucosa, increased ulcer index, and histopathological alterations. Indomethacin also increased lipid peroxidation, decreased the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase, increased the immunoreactivity of the inflammatory markers cyclo-oxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-α), and nuclear factor-kappa B (NF-κB), increased the transcription of the apoptotic marker, Bax, and decreased that of the antiapoptotic Bcl-2. Indomethacin also decreased the immunoreactivity of transforming growth factor-beta 1 (TGF-β1). On the other hand, pretreatment with apigenin (10 and 20mg/kg) resulted in a dose-dependent improvement in the macroscopic and microscopic features of the gastric mucosa in a manner comparable to that of omeprazole. The gastroprotective effects of apigenin may be attributed to its anti-inflammatory, anti-antioxidant, and anti-apoptotic activities as well as enhancing the expression of TGF-β1. Further experimental and clinical research is required to confirm activity of apigenin as anti-ulcer agent.

Rapamycin and Starvation Mitigate Indomethacin-Induced Intestinal Damage through Preservation of Lysosomal Vacuolar ATPase Integrity.

Nonsteroidal anti-inflammatory drugs (NSAIDs) possess anti-inflammatory, antipyretic, and analgesic properties and are among the most commonly used drugs. Although the cause of NSAID-induced gastric ulcers is well understood, the mechanism behind small intestinal ulcers remains elusive. In this study, we examined the mechanism through which indomethacin (IM), a prominent NSAID, induces small intestinal ulcers, both in vitro and in vivo. In IEC6 cells, a small intestinal epithelial cell line, IM treatment elevated levels of LC3-II and p62. These expression levels remained unaltered after treatment with chloroquine or bafilomycin, which are vacuolar ATPase (V-ATPase) inhibitors. IM treatment reduced the activity of cathepsin B, a lysosomal protein hydrolytic enzyme, and increased the lysosomal pH. There was a notable increase in subcellular colocalization of LC3 with Lamp2, a lysosome marker, post IM treatment. The increased lysosomal pH and decreased cathepsin B activity were reversed by pretreatment with rapamycin (Rapa) or glucose starvation, both of which stabilize V-ATPase assembly. To validate the in vitro findings in vivo, we established an IM-induced small intestine ulcer mouse model. In this model, we observed multiple ulcerations and heightened inflammation following IM administration. However, pretreatment with Rapa or fasting, which stabilize V-ATPase assembly, mitigated the IM-induced small intestinal ulcers in mice. Coimmunoprecipitation studies demonstrated that IM binds to V-ATPase in vitro and in vivo. These findings suggest that IM induces small intestinal injury through lysosomal dysfunction, likely due to the disassembly of lysosomal V-ATPase caused by direct binding. Moreover, Rapa or starvation can prevent this injury by stabilizing the assembly. SIGNIFICANCE STATEMENT: This study elucidates the largely unknown mechanisms behind small intestinal ulceration induced by indomethacin and reveals the involvement of lysosomal dysfunction via vacuolar ATPase disassembly. The significance lies in identifying potential preventative interventions, such as rapamycin treatment or glucose starvation, offering pivotal insights that extend beyond nonsteroidal anti-inflammatory drugs-induced ulcers to broader gastrointestinal pathologies and treatments, thereby providing a foundation for novel therapeutic strategies aimed at a wide array of gastrointestinal disorders.

Probiotic bacteria protect against indomethacin-induced gastric ulcers through modulation of oxidative stress, inflammation, and apoptosis.

Indomethacin is an anti-inflammatory drug that causes ulcers on the gastric mucosa due to its use. Probiotic bacteria are live microorganisms, and it has been stated by various studies that these bacteria have antioxidant and anti-inflammatory effects. In this study, we investigated the possible protective effect of various types of probiotic bacteria (Lactobacillus rhamnosus, Lactobacillus fermentum, and Lactobacillus brevis) against acute gastric mucosal damage caused by indomethacin. Control group - Physiological saline was administered daily for 10 days. Indo group-Physiological saline was administered daily for 10 days. Ranitidine + Indo group 5mg/kg ranitidine dose was administered daily for 5 days. On day 11, a single dose of 100mg/kg of indomethacin was given to the same group. Probiotic + Indo group 1ml/kg of oral probiotic bacteria was administered daily for 10 days. On day 11, a single 100mg/kg dose of indomethacin was given. After the application, the rats were anesthetized with ketamine xylazine, killed under appropriate conditions, the abdominal cavity was opened and the stomach tissues were removed. The obtained gastric tissues were used in the biochemical and histopathological analyses discussed below. All data were statistically evaluated by one-way ANOVA using SPSS 20.00, followed by Duncan Post hoc test. The data were expressed as mean ± SD. P < 0.05 was considered statistically significant. As a result, the administration of indomethacin caused gastric damage, stimulating oxidative stress, inflammation, and apoptosis. We found that the use of probiotic bacteria reduces oxidative stress (TOC), increases the activity of antioxidant enzymes (TAC), suppresses inflammation (IL-6 and Tnf-α), and inhibits apoptosis (Bax and Bcl-2) (P < 0.05). Probiotic treatment can mitigate gastric damage and apoptosis caused by indomethacin-induced gastric damage in rats. Probiotic also enhances the restoration of biochemical oxidative enzymes as it has anti-inflammatory, antioxidant, and antiapoptotic properties.

Indomethacin restrains cytoplasmic nucleic acid-stimulated immune responses by inhibiting the nuclear translocation of IRF3.

The recognition of cytosolic nucleic acid triggers the DNA/RNA sensor-IRF3 axis-mediated production of type I interferons (IFNs), which are essential for antiviral immune responses. However, the inappropriate activation of these signaling pathways is implicated in autoimmune conditions. Here, we report that indomethacin, a widely used nonsteroidal anti-inflammatory drug, inhibits nucleic acid-triggered IFN production. We found that both DNA- and RNA-stimulated IFN expression can be effectively blocked by indomethacin. Interestingly, indomethacin also prohibits the nuclear translocation of IRF3 following cytosolic nucleic acid recognition. Importantly, in cell lines and a mouse model of Aicardi-Goutières syndrome, indomethacin administration blunts self-DNA-induced autoimmune responses. Thus, our study reveals a previously unknown function of indomethacin and provides a potential treatment for cytosolic nucleic acid-stimulated autoimmunity.

Neutrophil extracellular trap formation and its implications in nonsteroidal anti-inflammatory drug-induced small intestinal injury.

Nonsteroidal anti-inflammatory drugs (NSAIDs) damage the small intestine via neutrophil infiltration driven by the mucosal invasion of enterobacteria. The antimicrobial function of neutrophils is partially dependent on neutrophil extracellular traps (NETs). Excessive NET formation has been associated with several inflammatory diseases. Here, we aimed to investigate the role of NETs in NSAID-induced small intestinal damage using human samples and an experimental mouse model. Human small intestine specimens were obtained from NSAID users during double-balloon enteroscopy. Wild-type, protein arginine deiminase 4 (PAD4) knockout, and antibiotic-treated mice were administered indomethacin to induce small intestinal injury. The expression of NET-associated proteins, including PAD4, citrullinated histone H3 (CitH3), cell-free DNA, and myeloperoxidase (MPO), was evaluated. The double-positive stained area with CitH3 and MPO, which is specific for neutrophil-derived extracellular traps, was significantly high in the injured small intestinal mucosa of NSAID users. In a mouse model, small intestinal damage developed at 6h after indomethacin administration, accompanied by increased mRNA levels of interleukin-1β and keratinocyte chemoattractant and elevated NET-associated protein levels of PAD4, CitH3, and MPO in small intestine and serum levels of cell-free DNA. Both genetic deletion and pharmacological inhibition of PAD4 attenuated this damage by reducing the mRNA expression of inflammatory cytokines and NET-associated proteins. Furthermore, mice pretreated with antibiotics showed resistance to indomethacin-induced small intestinal damage, with less NET formation. These results suggest that NETs aggravate NSAID-induced small intestinal injury. Therefore, NET inhibition could be a potential treatment for NSAID-induced small intestinal injury.

Indomethacin with or without prophylactic pancreatic stent placement to prevent pancreatitis after ERCP: a randomised non-inferiority trial

The combination of rectally administered indomethacin and placement of a prophylactic pancreatic stent is recommended to prevent pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk patients. Preliminary evidence suggests that the use of indomethacin might eliminate or substantially reduce the need for stent placement, a technically complex, costly, and potentially harmful intervention. In this randomised, non-inferiority trial conducted at 20 referral centres in the USA and Canada, patients (aged ≥18 years) at high risk for post-ERCP pancreatitis were randomly assigned (1:1) to receive rectal indomethacin alone or the combination of indomethacin plus a prophylactic pancreatic stent. Patients, treating clinicians, and outcomes assessors were masked to study group assignment. The primary outcome was post-ERCP pancreatitis. To declare non-inferiority, the upper bound of the two-sided 95% CI for the difference in post-ERCP pancreatitis (indomethacin alone minus indomethacin plus stent) would have to be less than 5% (non-inferiority margin) in both the intention-to-treat and per-protocol populations. This trial is registered with ClinicalTrials.gov (NCT02476279), and is complete. Between Sept 17, 2015, and Jan 25, 2023, a total of 1950 patients were randomly assigned. Post-ERCP pancreatitis occurred in 145 (14·9%) of 975 patients in the indomethacin alone group and in 110 (11·3%) of 975 in the indomethacin plus stent group (risk difference 3·6%; 95% CI 0·6-6·6; p=0·18 for non-inferiority). A post-hoc intention-to-treat analysis of the risk difference between groups showed that indomethacin alone was inferior to the combination of indomethacin plus prophylactic stent (p=0·011). The relative benefit of stent placement was generally consistent across study subgroups but appeared more prominent among patients at highest risk for pancreatitis. Safety outcomes (serious adverse events, intensive care unit admission, and hospital length of stay) did not differ between groups. For preventing post-ERCP pancreatitis in high-risk patients, a strategy of indomethacin alone was not as effective as a strategy of indomethacin plus prophylactic pancreatic stent placement. These results support prophylactic pancreatic stent placement in addition to rectal indomethacin administration in high-risk patients, in accordance with clinical practice guidelines. US National Institutes of Health.

Reactive oxygen species induced by indomethacin enhance accumulation of heme carrier protein 1 and hematoporphyrin accumulation in vitro and in vivo in a brain tumor model.

Photodynamic therapy (PDT) is useful for various cancers such as high-grade glioma and cancers of other organs. However, the mechanism of tumor-specific accumulation of porphyrin is not clear. The authors previously reported that heme carrier protein 1 (HCP1) contributes to the transport of porphyrins; specifically, we showed that the production of cancer-specific reactive oxygen species from mitochondria (mitROS) leads in turn to enhanced HCP1 expression. Indomethacin (IND), a non-steroidal anti-inflammatory drug, increases ROS production by affecting mitochondrial electron transfer system. In the present work, the authors investigated the effect of pretreatment with IND on cancer-specific porphyrin accumulation, using both a glioma cell line and a rat brain tumor model. This work demonstrated that exposure of a rat glioma cell to IND results in increased generation of cancer-specific mitROS and accumulation of HCP1 expression and porphyrin concentration. Additionally, systemic dosing of a brain tumor animal model with IND resulted in elevated cellular accumulation of porphyrin in tumor cell. This is an effect not seen with normal brain tissue. Thus, the administration of IND increases intracellular porphyrin concentrations in tumor cell without exerting harmful effects on normal brain tissue, and increased porphyrin concentration in tumor cell may lead to improved PDT effect.

Gastroprotective effect of Vien Khoi Tim capsules on indomethacin-induced gastric ulcers in rats

Available anti-ulcer drugs unveil partial effectiveness and numerous adverse reactions. Plants offer an alternative strategy in the search for new drugs in the therapy and prevention of peptic ulceration. The present study investigated the possible protective effect of the herbal formulation Vien Khoi Tim (VKT) on indomethacin-induced gastric mucosal damage in rats. VKT was tested at two doses (1.44 &amp; 0.48 capsules/kg/d po) ten days before the indomethacin single-dose challenge (40 mg/kg po). Animals were sacrificed six hours after indomethacin administration, and gastric tissues were collected for gross observation and histopathological analyses. The results revealed that the administration of indomethacin caused evident gastric mucosal damage with morphological and histological manifestations. VKT pretreatment tended to avert the rise in lesion numbers, reduce the ulcer index, and improve the severity of bleeding streaks and epithelial sloughing in gastric mucosa on the macroscopic examination compared to the model group. It is worth noting that no ulcerative lesions were observed in the gastric tissues of rats receiving VKT upon microscopic examination. Our results indicated that Vien Khoi Tim capsules might possess a protective role against indomethacin-induced gastric ulcers. Additional research is needed to better understand the mechanism by which Vien Khoi Tim capsules exert their gastroprotective effect.

Vasomotor reactivity measurement using Breath Holding Index to objectively diagnose migraine in Indonesia

Objective. Migraine is currently diagnosed using the subjective fulfilment of the International Headache Society (IHS) criteria. Considering the pathophysiology of endothelial dysfunction in migraine, this study aimed to utilize the breath holding index (BHI) to diagnose migraine objectively by assessing the vasodilatation response of intracranial arteries in migraine without aura. Material and method. 128 subjects with primary headache in the interictal phase were cross-sectional recruited and classified into migraine and non-migraine groups. BHI was performed using transcranial Doppler examination. Confirmed migraine was diagnosed using the validated IHS-equivalent Indonesian Migraine Screen Questionnaire (MS-Q) score of ≥4, BHI of &lt;0.69, and one-month clinical response to topiramate and/or indomethacin administration based on the nature of their headache. Result. This study enrolled 104 and 24 subjects with migraine and non-migraine headache, respectively. The sociodemographic profile was similar between groups. Reduced ipsilateral BHI was more observed in the migraine than the non-migraine group (0.70 vs 1.53, p&lt;0.001), with sensitivity of 49 (39-59) % and specificity of 92 (81-100) % using the established cut off value of 0.69. Conclusion. The breath holding index is a highly specific, moderately sensitive and objective tool to diagnose migraine. Measurement of vasoconstrictive response may be considered to further increase the sensitivity of this objective diagnostic tool.

Synergistic gastroprotective and antioxidative effects of natural olive oil and usnic acid isolated from Usnea longissima, a lichen species in Anatolia (Türkiye), in the indomethacin ulcer model created in rats

Usnea longissima, a medically important lichen growing up in forests in Anatolia (Turkey). In this study, the gastroprotective effect of usnic acid (UA) was investigated using an indomethacin (IND)-induced gastric ulcer model in rats. While 25, 50, 100 and 200 mg/kg UA doses were dissolved in 2 ml of olive oil (OO) and administered to rats, only OO was given to one group. In addition, lansoprazole (LAN) and ranitidine (RAN) and IND were dissolved in water and administered to rat groups. IND administration caused very high levels of damage to rat stomachs. On the other hand, when four doses of UA, OO, RAN and LAN were administered, it was determined that hyperemias in the stomach of rats was significantly reduced. After macroscopic analysis of gastric tissues, the activities of superoxide dismutase (SOD), catalase (CAT), myeloperoxidase (MPO) and nitric oxide synthase (iNOS and cNOS) enzymes as well as glutathione (GSH) and lipid peroxidation (LPO) levels were determined in these tissues. After IND application, it was detected increases in MPO, CAT and iNOS activities in gastric tissues and decreases in SOD, cNOS and GSH amounts. Four doses of UA, OO, RAN and LAN applications reversed the trend, bringing them closer to healthy levels.

Unravelling the Gastroprotective Potential of Kefir: Exploring Antioxidant Effects in Preventing Gastric Ulcers.

The present study was conducted to evaluate the protective effect of milk kefir against NSAID-induced gastric ulcers. Male Swiss mice were divided into three groups: control (Vehicle; UHT milk at a dose of 0.3 mL/100 g), proton pump inhibitor (PPI; lansoprazole 30 mg/kg), and 4% milk kefir (Kefir; 0.3 mL/100 g). After 14 days of treatment, gastric ulcer was induced by oral administration of indomethacin (40 mg/kg). Reactive oxygen species (ROS), nitric oxide (NO), DNA content, cellular apoptosis, IL-10 and TNF-α levels, and myeloperoxidase (MPO) enzyme activity were determined. The interaction networks between NADPH oxidase 2 and kefir peptides 1-35 were determined using the Residue Interaction Network Generator (RING) webserver. Pretreatment with kefir for 14 days prevented gastric lesions. In addition, kefir administration reduced ROS production, DNA fragmentation, apoptosis, and TNF-α systemic levels. Simultaneously, kefir increased NO bioavailability in gastric cells and IL-10 systemic levels. A total of 35 kefir peptides showed affinity with NADPH oxidase 2. These findings suggest that the gastroprotective effect of kefir is due to its antioxidant and anti-inflammatory properties. Kefir could be a promising natural therapy for gastric ulcers, opening new perspectives for future research.

Recovery from indomethacin-induced gastrointestinal bleeding by treatment with teprenone

BackgroundGastrointestinal injuries caused by nonsteroidal anti-inflammatory drugs (NSAIDs) is a serious side effect in patients with rheumatoid arthritis (RA). However, effective therapeutic strategies have yet to be established. In this study, we investigated the therapeutic effects of teprenone (TEP), a gastric mucosal protective drug, on NSAID-induced gastrointestinal injuries in rats with RA (AA rats).MethodsGastrointestinal injury was induced by oral administration of indomethacin (IMC), a typical NSAID. TEP was orally administered after IMC-induced gastrointestinal bleeding, and the stomach, jejunum, and ileum were excised.ResultsOn day 14 of IMC administration, lesion areas in the stomach, jejunum, and ileum were significantly larger in AA rats than in normal rats. When TEP was orally administered to AA rats, the lesion areas in the stomach, jejunum, and ileum significantly decreased compared with those in control rats (IMC-induced AA rats). Therefore, we measured NOS2 mRNA and NO levels, which were significantly decreased in rats with IMC-induced AA after treatment with TEP.ConclusionsThese results suggest that the oral administration of TEP may be useful for the treatment of NSAID-induced gastrointestinal injuries in patients with RA.

Evaluation of the Closure of Patent Ductus Arteriosus With Ibuprofen Compared to Indomethacin.

Limited data exist comparing indomethacin and ibuprofen for the treatment of patent ductus arteriosus (PDA). The objective was to compare the safety and efficacy of indomethacin and ibuprofen for treatment of PDA closure. This single-center, pre-test/post-test quasi-experiment included preterm infants admitted to the neonatal intensive care unit who received indomethacin (July 1, 2013-September 30, 2015) or ibuprofen (December 1, 2015-July 31, 2019) for PDA. Patients were excluded if they were thrombocytopenic, had existing kidney injury, unresolved intraventricular hemorrhage (IVH) or necrotizing enterocolitis (NEC) at treatment initiation. Data were obtained from the electronic health record. Study outcomes were complete PDA closure, degree of PDA closure, resolution of symptoms, and new-onset acute kidney injury (AKI), IVH, or NEC. A total of 114 patients were included: 44 (39%) received indomethacin and 70 (61%) received -ibuprofen. Twenty-one (21%) patients experienced successful PDA closure within 1 week: 13 (32%) indomethacin patients and 8 (13%) ibuprofen patients (p = 0.023). PDA size reduction occurred in 43 (46%) patients with 29 (25%) experiencing complete symptom resolution. Significantly more indomethacin patients compared with ibuprofen patients experienced new-onset AKI (48% vs 17%; p < 0.001) and received concomitant nephrotoxins (68% vs 39%; p = 0.002). There were no significant differences in new-onset IVH or NEC. Indomethacin administration successfully closed the PDA in more neonates than ibuprofen but resulted in higher rates of AKI. However, this was confounded by more frequent administration of concomitant nephrotoxins. Larger trials are needed to help elucidate the optimal drug for closure of the PDA in neonates.

Unveiling the interplay between NSAID-induced dysbiosis and autoimmune liver disease in children: insights into the hidden gateway to autism spectrum disorders. Evidence from ex vivo, in vivo, and clinical studies.

Autism spectrum disorders (ASD) represent a diverse group of neuropsychiatric conditions, and recent evidence has suggested a connection between ASD and microbial dysbiosis. Immune and gastrointestinal dysfunction are associated with dysbiosis, and there are indications that modulating the microbiota could improve ASD-related behaviors. Additionally, recent findings highlighted the significant impact of microbiota on the development of autoimmune liver diseases, and the occurrence of autoimmune liver disease in children with ASD is noteworthy. In the present study, we conducted both an in vivo study and a clinical study to explore the relationship between indomethacin-induced dysbiosis, autoimmune hepatitis (AIH), and the development of ASD. Our results revealed that indomethacin administration induced intestinal dysbiosis and bacterial translocation, confirmed by microbiological analysis showing positive bacterial translocation in blood cultures. Furthermore, indomethacin administration led to disturbed intestinal permeability, evidenced by the activation of the NLRP3 inflammasomes pathway and elevation of downstream biomarkers (TLR4, IL18, caspase 1). The histological analysis supported these findings, showing widened intestinal tight junctions, decreased mucosal thickness, inflammatory cell infiltrates, and collagen deposition. Additionally, the disturbance of intestinal permeability was associated with immune activation in liver tissue and the development of AIH, as indicated by altered liver function, elevated ASMA and ANA in serum, and histological markers of autoimmune hepatitis. These results indicate that NSAID-induced intestinal dysbiosis and AIH are robust triggers for ASD existence. These findings were further confirmed by conducting a clinical study that involved children with ASD, autoimmune hepatitis (AIH), and a history of NSAID intake. Children exposed to NSAIDs in early life and complicated by dysbiosis and AIH exhibited elevated serum levels of NLRP3, IL18, liver enzymes, ASMA, ANA, JAK1, and IL6. Further, the correlation analysis demonstrated a positive relationship between the measured parameters and the severity of ASD. Our findings suggest a potential link between NSAIDs, dysbiosis-induced AIH, and the development of ASD. The identified markers hold promise as indicators for early diagnosis and prognosis of ASD. This research highlights the importance of maintaining healthy gut microbiota and supports the necessity for further investigation into the role of dysbiosis and AIH in the etiology of ASD.

Protective Effects of Ethanol Extract from Hippophae rhamnoides L. Leaves against Indomethacin-Induced Gastric Ulcer in Rats

We aimed to determine the effects of ethanol extract of Hippophae rhamnoides L. leaves on indomethacin-induced gastric ulcer in rats. 35 male Sprague Dawley rats were divided into 7 groups (n=5) at random: healthy; Hippophae rhamnoides L. leaves ethanol extract (HR) III; indomethacin; indomethacin+famotidine; indomethacin+HRI (100 mg/kg); indomethacin +HRII (250 mg/kg) and indomethacin +HRIII (500 mg/kg). All rats except the healthy group fasted for 24 hours. At the end of this period, HR and famotidine (20 mg/kg) were administered by oral gavage to the corresponding rat groups. Five minutes after the HR treatments, 25 mg/kg of indomethacin was applied by oral gavage to all groups except the Healthy and HR III groups. Six hours after indomethacin administration, stomach tissues were removed for investigation macroscopic and biochemically (Superoxide dismutase activity, Glutathione, and Malondialdehyde levels). HR administration improved ulcerative injury in stomach tissues caused by the indomethacin-induced gastric ulcer. HR administration reduced indomethacin-induced ulcer areas. Moreover, HR treatment significantly decreased malondialdehyde levels, increased glutathione levels, and elevated superoxide dismutase activity. HR significantly improved gastric ulcer by alleviating oxidative stress that could be important in ulcer. HR may be a new potential treatment option for ulcer treatment with an antioxidant effect. These findings may provide a mechanistic basis for using HR leaves to treat gastric ulcer.

Antiulcer effects of the methanolic root extracts of Paulownia elongata on indomethacin-induced peptic ulcer in male albino rats

Medicinal plants have been the basis of treatment of various diseases in African traditional medicine as well as other forms of treatment from diverse cultures of the world. The aim of this study is to evaluate the Antiulcer Effects of the Ethanol Root Extracts of Paulownia elongata on Indomethacin-Induced Peptic Ulcer in Male Albino Rats. A total of sixteen (20) male albino rats gotten from the HEMA animal Farm, Federal Housing Estate Bajabure Gerie, ulcer was induced by administration of indomethacin (30 mg/kg, orally, Clinical isolates of four bacteria (Staphylococcus aureus, Pseudomonas aeruginosa, and Clostridium Bolulinum and Escherichia coli). The well method of the agar dilution was used to determine the antibacterial activity of the plant extracts. Were used for the antibacterial evaluation, and Gas Chromatography-Mass Spectrometry (GC-MS) analysis was used for phytochemical profiling. The study determined the phytochemical profile of methanol extracts of Paulownia elongate roots using GC-MS as displayed 20 chemical constituents, the antibacterial potential of the roots extract showed higher activity at 300 mg/kg/bwt with 18.12 + 0.9 mm on Salmonella typhi and at 400 mg/kg/bwt with inhibition rate 20.14+ 0.0 mm on Klebsiella pneumonia. The anti-ulcer potential was observed higher at 400 mg/kg/bwt in group 7 with potential of 87.71%. This activity of the crude roots extract was possible as a result of the chemical constituent observed. Thus this extract should be used as an agents to cutile diseases such as anti-microbials, anti-ulcer and well as diseases as cancer, HIV in the near feature with more research to isolate the active compounds.

Gastro-protective Effect of Corn Diet against Indomethacin Induced Ulceration in Experimental Rats

Introduction: One of the most prevalent gastrointestinal ailments is gastric ulcer, which is caused by an imbalance between protective and aggressive factors. Zea mays Corn is a significant cereal crop containing natural phytochemical substances that are sources of nourishment. The methanolic extract of Corn, according to a previous study, lowers stomach acidity and inhibits the percentage of gastric ulceration with no knowledge on the mechanisms involved.&#x0D; Aim: This study investigated the underlying gastroprotective mechanisms of the Corn diet (ZD).&#x0D; Materials and Methods: Sixty male Wistar rats were used, randomly grouped into 6; 1(Normal control), 2(Ulcerated control), 3, 4, 5 (prefed with ZD -55%, 65%, 75%) and 6 (cimetidine- 25mg/kg) for 28 days. Gastric ulcer was induced by oral administration of indomethacin (40mg/kg) and animals were sacrificed after 4 hours. The stomach was excised and cleaned, it was then homogenized and centrifuged for biochemical assays.&#x0D; Results: There is a significant reduction in gastric ulcer area in all treated groups. Significant increase in gastric tissue mucin content and gastric mucosal SOD, NO and PGE2 levels and significant reduction in the MDA was observed in the ZD and cimetidine group. Histological evaluation showed tubular glands closely packed and separated from each other by laminar propia, however there is mild presence of inflammatory cells within the laminar propia in the ZD groups compared to ulcerated control group that showed moderate oedema with infiltration of inflammatory cells with mild vascular congestion in the mucosa. There is significant reduction in the macroscopic gastric mucosal lesions with percentage inhibition of 90%, 92%, 90% and 92% in the ZD (55%, 65% and 75%) and cimetidine group respectively.&#x0D; Conclusion: Results obtained from this study suggests that Zm diet may have anti-ulcerogenic properties by enhancing antioxidant enzymes as well as, nitric oxide and prostaglandin E2 mechanisms.

Indomethacin Prophylaxis Is Associated with Reduced Risk of Intraventricular Hemorrhage in Extremely Preterm Infants Born in the Context of Amniotic Infection Syndrome

Background: Amniotic infection syndrome (AIS) with perinatal inflammation may increase the susceptibility to intraventricular hemorrhage (IVH) in preterm infants. Given its anti-inflammatory and ductus arteriosus constricting capacities, we hypothesized that prophylactic administration of indomethacin reduces the incidence, severity, and consequences of IVH in the context of perinatal inflammation. Methods: We evaluated data of infants born between 2009 and 2020 of 22 + 0–25+6 weeks of gestation from 68 German Neonatal Network centers. The effect of indomethacin prophylaxis on outcomes was analyzed in univariate analyses and multivariate regression models including a subgroup of infants with available data on 5-year follow-up. Results: 4760 infants were included with a median gestational age of 24.6 SSW [interquartile range (IQR) 24.1w–25.2w] and a birth weight of 640 g [IQR 550–750 g]. 1767/4760 (37.1%) preterm infants were born in the context of AIS and 527/4760 (11.1%) received indomethacin prophylaxis. AIS infants receiving prophylactic indomethacin had lower rates of IVH (32.7% vs. 36.9%, p = 0.04), IVH III/IV (9.7% vs. 16.0%, p = 0.02) and the combined outcome of severe IVH or death (15.9% vs. 23.2%, p = 0.01) as compared to infants without prophylaxis. Multivariate logistic regression analyses confirmed our observations. In a subgroup analysis of 730 preterm infants at 5 years of age, we did not find any correlation between prophylactic indomethacin and intelligence quotient <70 or cerebral palsy. Conclusions: Our observational data demonstrate that prophylactic indomethacin is associated with a reduced risk of IVH in the highly vulnerable subgroup of preterm infants <26 weeks of gestation born from AIS.

Gastroprotective effect of electrical spinal cord stimulation may be mediated by glucocorticoids produced in response to this stimulation

We demonstrated previously that stress-induced glucocorticoids are gastroprotective hormones but not ulcerogenic ones (Filaretova et al., 2016). Recently electrical spinal cord stimulation began to be used for both experimental studies of motor functions regulation and rehabilitation of motor functions in patients with spinal cord injury (Gerasimenko et al., 2021; Moshonkina et al., 2016). The spinal cord stimulation directed to the activation of spinal locomotor related networks affected visceral systems as well. Recently in our teamwork we have shown that the electrical spinal cord stimulation can cause an increase in blood glucocorticoid level accompanied by a gastroprotective effect (Filaretova et al., 2022). The aim of the present work was to verify the hypothesis that the gastroprotective effect of the electrical spinal cord stimulation may be mediated by glucocorticoids produced in response to this stimulation. Gastric injury was induced in anesthetized rats by prolonged gastric ischemia/reperfusion (I/R, 30 min occlusion of celiac artery followed by 3 h of reperfusion) or indomethacin administration (IM, 35 mg/kg, sc). For spinal stimulation, stainless steel wire electrodes were fixed in fasciae between T11-12 and L1–L2 vertebrae of anesthetized animals. Motor evoked responses in hindlimbs muscles to spinal stimulation were recorded. Spinal stimulation at 30 Hz was carried out with a subthreshold current for inducing muscle contractions (80% of the threshold). Sham-stimulated (control) rats were subjected to the same manipulations except for the stimulation itself. To test the participation of glucocorticoids in the gastroprotective effect of the stimulation, two approaches were used: pretreatment by the inhibitor of glucocorticoid synthesis, metyrapone (30 mg/kg, i.p.) and the antagonist of glucocorticoid receptors RU-38486 (20 mg/kg, i.p.). The concentration of corticosterone in blood plasma was determined using commercial ELISA kits. In control rats the spinal cord stimulation resulted in an increase of blood corticosterone level 1 h later. The spinal stimulation, applied 1 h before the onset of ulcerogenic stimuli, also significantly attenuated gastric erosion formation induced by I/R and IM as well. Metyrapone injected shortly before the stimulation caused a fast inhibition of corticosterone response and reversed the gastroprotective effect stimulation. The gastroprotective effect of the stimulation was also prevented by the pretreatment rats with glucocorticoid receptor antagonist RU-38486. The obtained results indicate on contribution of glucocorticoids to gastroprotective effect of spinal cord stimulation. In conclusion, the findings support the hypothesis that the gastroprotective effect of the electrical spinal cord stimulation may be mediated by glucocorticoids produced in response to this stimulation. The study was supported by the Ministry of Education and Science of the Russian Federation (agreement No. 075-15-2020-921 for the creation and development of the world-class scientific center “Pavlov Center “Integrative Physiology - to medicine, high-tech healthcare and technologies of stress resistance”). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Manganese abated indomethacin-induced gastrohepatorenal toxicities in Rats via suppression of oxidative stress, polyamine catabolism, inflammation and activation of Caspase-3

Indomethacin (IND) is a non-steroidal anti-inflammatory drug with many therapeutic benefits and multi-organ toxicities. Manganese (Mn) is a trace metal essential in many biological processes. However, there is dearth of information concerning the effect of Mn on IND-induced gastrohepatorenal damage in rats. This study investigated the mitigating effect of manganese on IND-induced gastrohepatorenal damage in rats. Adult male rats were assigned into four groups of eight rats each and were treated once daily for 14 days. Group 1 served as control; group 2 received IND alone (5 mg/kg); group 3 received IND (5 mg/kg) and Mn alone (10 mg/kg) and group 4 received Mn alone Mn alone (10 mg/kg). Administration of IND significantly increased ulcer score, ulcer index, titrable acidity and peptic activity and decreased pH, mucus content, hexosamine and sialic acid levels. IND also increased hepatorenal markers, myeloperoxidase (MPO), nitric oxide (•NO), malondialdehyde (MDA), lipid hydroperoxide (LOOH), protein carbonyl (PCO), spermine oxidase (SpmOX), putrescine Oxidase (PutOX), tumor necrosis factor-α (TNF-α) interleukin-1β (IL-1β), caspase-3 and decreased the activities of superoxide dismutase (SOD), catalase, glutathione S-transferase (GST), glutathione peroxidase (GPx) and glutathione (GSH) level relative to control. Co-administration of IND and Mn significantly decreased ulcerogenic parameters, hepatorenal markers, MPO, •NO, MDA, LOOH, PCO, SpmOX, PutOX, TNF-α, IL-1β, caspase-3 and increased antioxidant status relative to IND alone group.Histological examination showed that injuries induced by IND were ameliorated by Mn rats.Mn suppressed IND-induced oxidative stress, inflammation, polyamine catabolism and caspase-3 activation in the liver and kidney of the rats.