RESUMEN
We studied the effect of enteral administration of GABA on the gastric mucosa in male Wistar rats (n=47) with modeled metabolic stress (food deprivation for 9 days with free access to water). The relative weights of the adrenal glands and thymus were determined, and histological examination of the stomach was performed. In control rats, modeling the metabolic stress was accompanied by the development of erosive damage to the gastric mucosa related to blood supply disturbances. Administration of GABA prevented erosions and exhibited a pronounced gastroprotective effect. Thus, administration of GABA can be a promising method for the prevention and treatment of erosive gastric lesions associated with metabolic stress.
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Mucosa Gástrica , Ratas Wistar , Estrés Fisiológico , Ácido gamma-Aminobutírico , Animales , Masculino , Ácido gamma-Aminobutírico/metabolismo , Ácido gamma-Aminobutírico/farmacología , Ratas , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Estrés Fisiológico/efectos de los fármacos , Glándulas Suprarrenales/efectos de los fármacos , Glándulas Suprarrenales/metabolismo , Glándulas Suprarrenales/patología , Timo/efectos de los fármacos , Timo/patología , Timo/metabolismo , Privación de Alimentos , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patología , Úlcera Gástrica/prevención & control , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológicoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Eucalyptus genus has been used for a very long time in conventional treatment as an anti-ulcer remedy. AIM OF THE STUDY: The study aimed to explore the gastroprotective potential of 7-O-methyl aromadendrin (7-OMA), and sakuranetin (SKN) in comparison with omeprazole. The study tackled the contribution of their anti-inflammatory, antioxidant, and antiapoptotic capabilities to their anti-gastric ulcer effects. MATERIALS AND METHODS: An ethanol-induced gastric ulcer model in rats was adopted and the consequences were confirmed by a molecular docking study. RESULTS: The oral pretreatment of rats 1 h before ethanol using omeprazole (20 mg/kg) or 7-OMA (20 or 40 mg/kg) or SKN (20 or 40 mg/kg) exhibited gastroprotective and anti-inflammatory properties to different extents. These amendments witnessed as restorations in the stomach histological architecture in H and E-stained sections, mucus content in periodic acid-Schiff (PAS) stained sections with increased cellular proliferation, as demonstrated by increased immunohistochemical staining of PCNA, and increments in stomach COX-1 activity and eNOS. The highest dose of SKN showed the best corrections to reach 4.8, 1.8, and 2.1 folds increase in PAS, COX-1 and eNOS, respectively as compared to the untreated ethanol-induced gastric ulcer group; effects that were comparable to that of omeprazole. Moreover, reductions in COX-2 activity, and the protein expression of NF-κB, IL-6, TNF-α and NOx, in addition to the gene expression of inducible iNOS were also noted. Moreover, the antioxidant and antiapoptotic capabilities of omeprazole, 7-OMA, and SKN were perceived. SKN (40 mg/kg) succeeded to show the unsurpassed results to reach 293.6%, 237.1%, 274.7%, 248.2%, and 175.4% in total and reduced GSH, catalase, SOD, and Bcl2, respectively, as well as 50.0%, 46.8%, and 52.1 % in oxidized GSSG, TBARS and caspase-3, respectively. The gastroprotective potential of the tested compounds can be assigned to their anti-inflammatory, antioxidant and antiapoptotic properties.7-OMA and SKN were studied using molecular docking into the binding sites of the most significant inflammatory targets, including COX-2, TNF-α, iNOS, and NF-κB. Pharmacokinetic and physicochemical parameters in silico were appropriate. CONCLUSION: The prophylactic use of 7-OMA and SKN could be considered as an add-on to recurrent gastric ulcers and might influence its therapeutic approaches.
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Antiinflamatorios , Antiulcerosos , Antioxidantes , Etanol , Simulación del Acoplamiento Molecular , Estrés Oxidativo , Úlcera Gástrica , Animales , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patología , Estrés Oxidativo/efectos de los fármacos , Antiulcerosos/farmacología , Masculino , Antiinflamatorios/farmacología , Etanol/química , Ratas , Antioxidantes/farmacología , Ratas Wistar , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Mucosa Gástrica/metabolismo , Flavonoides/farmacología , Omeprazol/farmacología , Apoptosis/efectos de los fármacos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , FitoalexinasRESUMEN
Aberration of the gastric mucosal barrier homeostasis circuit is one of the key features linked to the onset of gastric ulcers (GU). This work aimed to inspect the gastroprotective influence of dimethyl fumarate (DMF) on ethanol-induced GU in rats and to decipher the possible mechanisms entailed. Rats were pretreated with either DMF (80 mg/kg) or omeprazole (OMP) (20 mg/kg) by oral gavage for 2 weeks. After 24 h of starvation, ethanol (5 ml/kg, oral) was employed to trigger GU in rats, while carboxymethyl cellulose (CMC) was used as a control. Ethanol notably elevated both macroscopic and microscopic gastric damage. DMF and OMP exhibited similar effects on gastric ulcer healing. DMF intervention led to a substantial improvement in gastric insults. DMF significantly reduced ethanol-triggered gastric lesions, as manifested by decreased gastric secretion, acidity, ulcer surface area percent, reduced leukocyte incursion, and increased mucus percent. DMF upregulated miR-34a-5p expression concomitant with the suppression of high mobility group box1 (HMGB1) and inflammatory responses in gastric mucosal homogenate. DMF improved GU by restoring reduced antioxidant defense mechanisms through the coactivation of nuclear factor erythroid 2-related factor-2 (Nrf2), peroxisome proliferator-activated receptor gamma (PPARγ), and sirtuin1 (SIRT1), indicating the protective role of the PPARγ/SIRT1/Nrf2 pathway. Intriguingly, DMF mitigated apoptosis in ethanol-elicited GU. Taken together, this research implies the potential for the repurposing of DMF as an innovative gastroprotective medication to reestablish the balance of the gastric mucosal barrier via the attenuation of gastric inflammation, oxidative stress, and apoptosis.
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Dimetilfumarato , Etanol , Proteína HMGB1 , MicroARNs , Factor 2 Relacionado con NF-E2 , PPAR gamma , Sirtuina 1 , Úlcera Gástrica , Receptor Toll-Like 4 , Animales , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/patología , Etanol/toxicidad , Etanol/efectos adversos , Sirtuina 1/metabolismo , Sirtuina 1/genética , Factor 2 Relacionado con NF-E2/metabolismo , Dimetilfumarato/farmacología , Dimetilfumarato/uso terapéutico , Ratas , MicroARNs/metabolismo , MicroARNs/genética , Masculino , Proteína HMGB1/metabolismo , Proteína HMGB1/genética , PPAR gamma/metabolismo , Receptor Toll-Like 4/metabolismo , Transducción de Señal/efectos de los fármacos , FN-kappa B/metabolismo , Ratas WistarRESUMEN
Gastric ulcer is a highly prevalent digestive tract disease across the world, which is recurrent and hard to cure, sometimes transforming into gastric cancer if left untreated, posing great threat to human health. To develop new medicines for gastric ulcer, we ran a series of screens with ethanol stress model in GES-1 cells, and we uncovered that lamivudine rescued cells from ethanol toxicity. Then, we confirmed this discovery using the well-established ethanol-induced gastric ulcer model in mice and our findings suggest that lamivudine can directly activate phosphoglycerate kinase 1 (PGK1, EC 2.7.2.3), which binds and stimulates superoxide dismutase 1 (SOD1, EC 1.15.1.1) to inhibit ferroptosis and ultimately improve gastric ulcer. Moreover, AAV-PGK1 exhibited comparable gastroprotective effects to lamivudine. The findings are expected to offer novel therapeutic strategies for gastric ulcer, encompassing both lamivudine and AAV-PGK1.
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Ferroptosis , Lamivudine , Ratones Endogámicos C57BL , Fosfoglicerato Quinasa , Úlcera Gástrica , Animales , Úlcera Gástrica/prevención & control , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patología , Ratones , Fosfoglicerato Quinasa/metabolismo , Fosfoglicerato Quinasa/genética , Ferroptosis/efectos de los fármacos , Ferroptosis/fisiología , Humanos , Lamivudine/farmacología , Masculino , Etanol , Línea Celular , Superóxido Dismutasa-1/metabolismo , Superóxido Dismutasa-1/genéticaRESUMEN
INTRODUCTION: Gastric ulcer is one of the most common and serious conditions in the gastrointestinal tract. One of the main causes of gastric ulcers is using of non-steroidal anti-inflammatory drugs (NSAIDs) which have limited their use in clinical practice. Several studies have revealed that metformin and Vitamin C (Vit C) exhibit protective effects against gastric mucosal damage in different animal models. However, no studies indicate their combination's effect on gastric ulcer models. Therefore, this study aims to investigate the protective effects of metformin and Vit C combination on indomethacin-induced gastric ulcers. MATERIAL AND METHODS: In total, thirty rats were divided into six groups, including the control group, rats received indomethacin (50 mg/kg, i.p.), rats received indomethacin and pretreated with ranitidine (100 mg/kg), metformin (100 mg/kg, i.p.), Vit C (100 mg/kg), or metformin combined with Vit C. Four hours after indomethacin administration, rats were euthanized, and gastric tissues were removed for macroscopic, histopathologic, and biochemical examinations. RESULTS: All therapeutics used in this study were found to alleviate gastric mucosal injury caused by indomethacin, as observed in histopathologic and macroscopic evaluations. Both Vit C and metformin were observed to significantly decrease lipid peroxidation and enhance the activity of anti-oxidative enzymes, SOD, GPx, and catalase. However, a more significant effectiveness was observed in catalase and GPx activities when Vit C was co-administered with metformin. CONCLUSIONS: In conclusion, the present study revealed that metformin and Vit C combination therapy could potentially treat gastric ulcers associated with indomethacin.
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Antiinflamatorios no Esteroideos , Ácido Ascórbico , Mucosa Gástrica , Indometacina , Metformina , Úlcera Gástrica , Animales , Metformina/farmacología , Indometacina/toxicidad , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/patología , Ácido Ascórbico/farmacología , Ácido Ascórbico/uso terapéutico , Ratas , Masculino , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Mucosa Gástrica/metabolismo , Antiinflamatorios no Esteroideos/farmacología , Peroxidación de Lípido/efectos de los fármacos , Antioxidantes/farmacología , Modelos Animales de Enfermedad , Quimioterapia Combinada , Ratas Wistar , Antiulcerosos/farmacologíaRESUMEN
PURPOSE: This study aimed to evaluate the morbidity associated with excisional biopsy in patients with spontaneous gastric perforation. METHODS: A retrospective, single-center, observational study was performed. All consecutive patients with spontaneous gastric perforation who underwent surgical therapy were included. Outcomes were assessed concerning the performance of excisional biopsy. RESULTS: A total of 135 adult patients were enrolled. Of these, 110 (81.5%) patients underwent excisional biopsy, while 17 (12.6%) did not. The remaining eight (5.9%) patients who underwent gastric resection were excluded from the analysis. Patients undergoing excisional biopsy developed significantly higher rates of postoperative complications (p = 0.007) and experienced more severe complications according to the Clavien-Dindo classification, particularly type III and above (p = 0.017). However, no significant differences were observed regarding in-hospital mortality, reoperation, suture dehiscence, or length of hospital stay. CONCLUSION: Excisional biopsy for gastric perforation has been shown to be associated with increased morbidity. Surgical closure followed by early endoscopic biopsy may be a superior approach for gastric perforation management to rule out malignancy.
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Úlcera Péptica Perforada , Úlcera Gástrica , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Úlcera Gástrica/patología , Úlcera Gástrica/cirugía , Úlcera Péptica Perforada/cirugía , Úlcera Péptica Perforada/patología , Úlcera Péptica Perforada/mortalidad , Biopsia , Adulto , Complicaciones Posoperatorias/etiología , Anciano de 80 o más AñosRESUMEN
Equine Gastric Ulcer Syndrome (EGUS) occurs with variable prevalence in horses, donkeys, and mules. Due to the particularities of the mucous membranes, the syndrome is made up of Squamous Gastric Disease (ESGD) and Glandular Gastric Disease (EGGD). Given the multifactorial nature and multiple classification systems of the syndrome, significant differences have been reported between prevalence studies performed ante mortem, which are even more remarkable when compared with postmortem evaluations. This study aimed to determine the presence and grade of squamous gastric disease in horses, donkeys and mules immediately after slaughter. The postmortem examination considered the inspection of the squamous region (cardia, dorsal fundus, and margo plicatus) and the classification of the observed lesions. The general prevalence of ESGD in the entire population of study was 83.3 % (78 %, 89 %, and 83 % for horses, donkeys, and mules, respectively), compromising the margo plicatus in all cases. 75 % had more than 5 lesions and 50 % had deep lesions, lesions of varying severity and/or evidence of recent/active bleeding. The prevalence of ESGD was similar in horses, donkeys, and mules subjected to similar handling conditions prior to slaughter, including long-distance traveling, fasting, and stress factors.
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Equidae , Animales , Colombia/epidemiología , Prevalencia , Mataderos/estadística & datos numéricos , Gastropatías/veterinaria , Gastropatías/epidemiología , Gastropatías/patología , Caballos , Úlcera Gástrica/epidemiología , Úlcera Gástrica/veterinaria , Úlcera Gástrica/patología , Enfermedades de los Caballos/epidemiología , Enfermedades de los Caballos/patologíaRESUMEN
We evaluate the value of oral contrast-enhanced gastric ultrasonography (OCUS) by comparing it with conventional gastroscopy in diagnosing and staging benign peptic ulcer. From July 2018 to December 2020, 44 patients with gastroscopy-confirmed benign peptic ulcers (a total of 45 ulcers were detected), who also received OCUS, were retrospectively reviewed. Each patient's ultrasound images were compared with gastroscopy and pathology findings. The characteristics of ultrasonic images of different stages of ulcer were analysed. A total of 43 ulcers were detected by OCUS in 44 patients with benign peptic ulcers. There were no false positive results among the OCUS exams, but two ulcers were misdiagnosed. OCUS for benign peptic ulcer staging also shows acceptable clinical practice results. OCUS is useful for detecting and staging benign peptic ulcer, and may be considered an alternative method for conventional gastroscopy. OCUS is especially useful in the follow-up of BPU treatment, but futher study is needed to improve the diagnostic accuracy of benign and malignant ulcers.
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Medios de Contraste , Úlcera Péptica , Ultrasonografía , Humanos , Masculino , Femenino , Ultrasonografía/métodos , Persona de Mediana Edad , Úlcera Péptica/diagnóstico por imagen , Úlcera Péptica/patología , Anciano , Adulto , Estudios Retrospectivos , Gastroscopía/métodos , Estómago/diagnóstico por imagen , Estómago/patología , Anciano de 80 o más Años , Úlcera Gástrica/diagnóstico por imagen , Úlcera Gástrica/patologíaRESUMEN
BACKGROUND: Vanillic acid (VA; 4-hydroxy-3-methoxybenzoic acid) is a flavouring agent found in various natural sources such as olives, fruits, and green tea. While VA exhibits numerous pharmacological effects, its potential protective effects against gastric injury warrants further investigation. Therefore, the primary objective of this study is to elucidate investigate the gastroprotective properties of VA against ethanol-induced gastric injury. METHODS AND RESULTS: Rats were orally administered either saline or VA at different doses (50, 100, and 200 mg/kg/day), with omeprazole (20 mg/kg) serving as a positive control, for fourteen consecutive days before ethanol administration. Blood and gastric tissue samples were collected one hour after ethanol administration for biochemical, molecular, and histological analyses. Pre-treatment with VA before ulcer induction alleviated both macroscopic and microscopic damage. It also increased antioxidant glutathione levels and decreased malondialdehyde and myeloperoxidase activity, along with reducing inflammatory markers such as tumour necrosis factor (TNF)-α, interleukin (IL)-6, and nuclear factor kappa B (NF-κB). Additionally, VA pre-treatment reversed the elevation of Bax mRNA expression and gastric caspase-3 levels induced by gastric damage. It also mitigated the reduction in Bcl-2 mRNA expression. CONCLUSION: These findings suggest that VA exerts protective effects against ethanol-induced gastric injury in rats. It achieves this by augmenting gastric antioxidant capacity and mitigating oxidative, inflammatory, and apoptotic damage.
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Apoptosis , Etanol , FN-kappa B , Transducción de Señal , Úlcera Gástrica , Ácido Vanílico , Animales , FN-kappa B/metabolismo , Etanol/toxicidad , Etanol/efectos adversos , Ratas , Apoptosis/efectos de los fármacos , Ácido Vanílico/farmacología , Transducción de Señal/efectos de los fármacos , Masculino , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patología , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Mucosa Gástrica/metabolismo , Mucosa Gástrica/lesiones , Estrés Oxidativo/efectos de los fármacos , Antioxidantes/farmacología , Antioxidantes/metabolismo , Sustancias Protectoras/farmacología , Ratas Wistar , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/genética , Glutatión/metabolismoRESUMEN
Yucca filamentosa (YF) is widely used in folk medicine for its anti-inflammatory effects. Our study aimed to evaluate the chemical profile of YF extracts. Additionally, the gastroprotective efficacy of its crude leaf extract and nano-cubosomal formulation was assessed in a rat model of ethanol-induced gastric injury by altering the HMGB-1/RAGE/TLR4/NF-κB pathway. The phytochemical composition of YF was investigated using FTIR spectroscopy and LC-MS/MS techniques. Standardization was further accomplished using HPLC. Rats were treated orally with yucca crude extract or its nano-cubosomal formulation at doses of 25, 50, and 100 mg/kg. Famotidine (50 mg/kg, IP) was used as a reference drug. After 1 h, rats were administered ethanol (1 ml, 95 %, orally). One hour later, the rats were sacrificed, and the serum was separated to determine TNF-α and IL-6 levels. Stomachs were excised for the calculation of the ulcer index and histopathological examinations. Stomach tissue homogenate was used to determine MDA and catalase levels. Additionally, the expression levels of HMGB-1/RAGE/TLR4/NF-κB were assessed. Phytochemical analysis confirmed the predominance of steroidal saponins, sucrose, organic and phenolic acids, and kaempferol. The nano-cubosomal formulation demonstrated enhanced gastroprotective, anti-oxidant, and anti-inflammatory efficacy compared to the crude extract at all tested doses. The most prominent effect was observed in rats pretreated with the YF nano-cubosomal formulation at a dose of 100 mg/kg, which was similar to normal control and famotidine-treated rats. Our results highlighted the enhanced gastroprotective impact of the yucca nano-cubosomal formulation in a dose-dependent manner. This suggests its potential use in preventing peptic ulcer recurrence.
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Antiulcerosos , Etanol , Proteína HMGB1 , Extractos Vegetales , Hojas de la Planta , Úlcera Gástrica , Yucca , Animales , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Etanol/química , Hojas de la Planta/química , Masculino , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/patología , Proteína HMGB1/metabolismo , Ratas , Antiulcerosos/farmacología , Antiulcerosos/uso terapéutico , Antiulcerosos/química , Antiulcerosos/administración & dosificación , Yucca/química , FN-kappa B/metabolismo , Receptor Toll-Like 4/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Ratas Wistar , Nanopartículas/química , Interleucina-6/metabolismo , Interleucina-6/sangre , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/sangreRESUMEN
Clinopodium menthifolium (wood calamint) is a folkloric medicinal plant ingested as a treatment for many human disorders including gastric disorders. Our study evaluates the anti-ulcer potentials of Clinopodium menthifolium ethanol extracts (CMEE) in induced gastric ulcers in rats. Thirty Dawley male rats were divided into 5 groups: normal and ulcer controls, treated orally with Tween 20%; reference rats treated with Omeprazole 20 mg/kg, and the remaining two groups received 250 and 500 mg/kg CMEE for 2 weeks. After that, food was taken away for 24 h, and then, rats received ethanol-induced gastric ulceration (except normal control), 80% (1 ml/rat). After anesthetization and sacrificing, the ulcer index, mucus content, and other ulcer measurements were obtained from dissected rat stomachs. Stomach tissues were also analyzed by different histology procedures and homogenized stomach tissues were assessed for their antioxidant contents. The toxicity trial showed the absence of any toxic signs in rats supplemented with 2 and 5 g/kg of CMEE. The gastroprotective results showed a significantly lower ulcer index and higher gastric mucin content in CMEE-ingested rats compared to ulcer controls. Furthermore, CMEE treatments significantly increased the intensity of periodic acid Schiff stained (PAS), HSP 70 protein, and down-regulation of Bax protein expression in the stomach epithelium. Rats supplemented with 500 mg/kg revealed noticeable changes in their serum inflammatory cytokines along with positive regulations of antioxidant enzymes. The outcomes provide a scientific backup behind the gastroprotective potential effect of CMEE that could serve as a natural resource against peptic ulcers.
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Etanol , Extractos Vegetales , Úlcera Gástrica , Proteína X Asociada a bcl-2 , Animales , Etanol/efectos adversos , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patología , Ratas , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Masculino , Proteína X Asociada a bcl-2/metabolismo , Ratas Sprague-Dawley , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Mucosa Gástrica/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/patología , Inflamación/metabolismo , Proteínas de Choque Térmico/metabolismo , Antioxidantes/farmacología , Estómago/patología , Estómago/efectos de los fármacos , Antiulcerosos/farmacología , Antiulcerosos/uso terapéutico , Proteínas HSP70 de Choque Térmico/metabolismoRESUMEN
BACKGROUND: 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. METHODS: Control group - Physiological saline was administered daily for 10 days. Indo group-Physiological saline was administered daily for 10 days. Ranitidine + Indo group 5 mg/kg ranitidine dose was administered daily for 5 days. On day 11, a single dose of 100 mg/kg of indomethacin was given to the same group. Probiotic + Indo group 1 ml/kg of oral probiotic bacteria was administered daily for 10 days. On day 11, a single 100 mg/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. RESULTS: 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). CONCLUSION: 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.
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Apoptosis , Mucosa Gástrica , Indometacina , Inflamación , Estrés Oxidativo , Probióticos , Úlcera Gástrica , Indometacina/efectos adversos , Probióticos/farmacología , Animales , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/prevención & control , Úlcera Gástrica/patología , Úlcera Gástrica/metabolismo , Estrés Oxidativo/efectos de los fármacos , Apoptosis/efectos de los fármacos , Ratas , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Mucosa Gástrica/metabolismo , Inflamación/metabolismo , Masculino , Ratas Wistar , Antioxidantes/metabolismo , Antioxidantes/farmacologíaRESUMEN
BACKGROUND: Proton-pump inhibitors (PPIs) prevent aspirin-associated gastric and duodenal mucosal damage. However, long-term use of PPIs can lead to various adverse reactions, such as gastric polyps and enterochromaffin-like cell hyperplasia. Current research indicates that the abovementioned adverse reactions are mainly related to hypergastrinemia. We investigated whether low-frequency administration of omeprazole could effectively repair aspirin-induced mucosal damage and reduce the increase in gastrin levels associated with long-term use of PPIs. METHODS: SpragueâDawley rats were divided into four treatment groups: daily aspirin, daily aspirin and omeprazole once every day (qd), daily aspirin and omeprazole once every other day (qod), and daily aspirin and omeprazole once every three days (1/d3). After 15 days of feeding, blood samples were collected, and the stomachs of sacrificed rats were subjected to macroscopic, histological, and immunohistochemical studies. Moreover, in clinical practice, patients with peptic ulcers caused by aspirin took a standard dose of omeprazole (20 mg) every other day. Two months later, gastroscopy was performed to examine the healing of the ulcers. RESULTS: Both the omeprazole qd and omeprazole qod administrations effectively prevented aspirin-induced gastric peptic ulcers, with no significant difference between the two groups in the inhibition of parietal cell secretion of gastric acid and cell apoptosis. However, omeprazole 1/d3 failed to completely prevent aspirin-induced gastric mucosal injury. Notably, the gastrin levels, cell proliferation ability and cholecystokinin B receptor expression of the omeprazole qd group were significantly higher than those of the omeprazole qod group. In clinical work, patients with peptic ulcers caused by aspirin were given a standard dose of omeprazole every other day, and their ulcers healed after 2 months, as observed by gastroscopy. CONCLUSIONS: Omeprazole administration once every other day can effectively prevent aspirin-induced peptic ulcers and reduce hypergastrinemia, which may reduce the long-term adverse effects of PPI treatment.
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Aspirina , Mucosa Gástrica , Gastrinas , Omeprazol , Inhibidores de la Bomba de Protones , Ratas Sprague-Dawley , Animales , Aspirina/efectos adversos , Aspirina/administración & dosificación , Omeprazol/farmacología , Omeprazol/administración & dosificación , Inhibidores de la Bomba de Protones/farmacología , Inhibidores de la Bomba de Protones/administración & dosificación , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Gastrinas/sangre , Masculino , Ratas , Esquema de Medicación , Humanos , Úlcera Péptica/prevención & control , Úlcera Péptica/inducido químicamente , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Mucosa Intestinal/metabolismo , Úlcera Gástrica/prevención & control , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/patologíaRESUMEN
OBJECTIVE: To improve the biological and toxicological properties of Mefenamic acid (MA), the galactosylated prodrug of MA named MefeGAL was included in polymeric solid dispersions (PSs) composed of poly(glycerol adipate) (PGA) and Pluronic® F68 (MefeGAL-PS). MefeGAL-PS was compared with polymeric solid formulations of MA (MA-PS) or a mixture of equal ratio of MefeGAL/MA (Mix-PS). METHODS: The in vitro and in vivo pharmacological and toxicological profiles of PSs have been investigated. In detail, we evaluated the anti-inflammatory (carrageenan-induced paw edema test), analgesic (acetic acid-induced writhing test) and ulcerogenic activity in mice after oral treatment. Additionally, the antiproliferative activity of PSs was assessed on in vitro models of colorectal and non-small cell lung cancer. RESULTS: When the PSs were resuspended in water, MefeGAL's, MA's and their mixture's apparent solubilities improved due to the interaction with the polymeric formulation. By comparing the in-vivo biological performance of MefeGAL-PS with that of MA, MefeGAL and MA-PS, it was seen that MefeGAL-PS exhibited the same sustained and delayed analgesic and anti-inflammatory profile as MefeGAL but did not cause gastrointestinal irritation. The pharmacological effect of Mix-PS was present from the first hours after administration, lasting about 44â¯hours with only slight gastric mucosa irritation. In-vitro evaluation indicated that Mix-PS had statistically significant higher cytotoxicity than MA-PS and MefeGAL-PS. CONCLUSIONS: These preliminary data are promising evidence that the galactosylated prodrug approach in tandem with a polymer-drug solid dispersion formulation strategy could represent a new drug delivery route to improve the solubility and biological activity of NSAIDs.
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Sistemas de Liberación de Medicamentos , Ácido Mefenámico , Animales , Ácido Mefenámico/farmacología , Ácido Mefenámico/administración & dosificación , Ratones , Humanos , Masculino , Edema/tratamiento farmacológico , Edema/inducido químicamente , Antiinflamatorios/farmacología , Antiinflamatorios/administración & dosificación , Profármacos/farmacología , Profármacos/administración & dosificación , Analgésicos/farmacología , Analgésicos/administración & dosificación , Analgésicos/toxicidad , Proliferación Celular/efectos de los fármacos , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/toxicidad , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/patología , Poloxámero/químicaRESUMEN
Antidepressant duloxetine has been shown protective effect on indomethacin-induced gastric ulcer, which was escorted by inflammation in the gastric mucosa. Cytokines are the principal mediators of inflammation. Thus, by screening the differential expression of cytokines in the gastric mucosa using cytokine array at 3 h after indomethacin exposure, when the gastric ulcer began to format, we found that indomethacin increased cytokines which promoted inflammation responses, whereas duloxetine decreased pro-inflammatory cytokines increased by indomethacin and increased RANTES expression. RANTES was consistently increased by pretreated with both 5 mg/kg and 20 mg/kg duloxetine at 3 h and 6 h after indomethacin exposure in male rats. Selective blockade of RANTES-CCR5 axis by a functional antagonist Met-RANTES or a CCR5 antagonist maraviroc suppressed the protection of duloxetine. Considering the pharmacologic action of duloxetine on reuptake of monoamine neurotransmitters, we examined the serotonin (5-HT), norepinephrine and dopamine contents in the blood and discovered 20 mg/kg duloxetine increased 5-HT levels in platelet-poor plasma, while treatment with 5-HT promoted expression of RANTES in the gastric mucosa and alleviated the indomethacin-induced gastric injury. Furthermore, duloxetine activated PI3K-AKT-VEGF signaling pathway, which was regulated by RANTES-CCR5, and selective inhibitor of VEGF receptor axitinib blocked the prophylactic effect of duloxetine. Furthermore, duloxetine also protected gastric mucosa from indomethacin in female rats, and RANTES was increased by duloxetine after 6 h after indomethacin exposure too. Together, our results identified the role of cytokines, particularly RANTES, and the underlying mechanisms in gastroprotective effect of duloxetine against indomethacin, which advanced our understanding in inflammatory modulation by monoamine-based antidepressants.
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Quimiocina CCL5 , Clorhidrato de Duloxetina , Mucosa Gástrica , Indometacina , Proteínas Proto-Oncogénicas c-akt , Ratas Sprague-Dawley , Serotonina , Transducción de Señal , Úlcera Gástrica , Factor A de Crecimiento Endotelial Vascular , Animales , Clorhidrato de Duloxetina/farmacología , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Mucosa Gástrica/metabolismo , Masculino , Indometacina/toxicidad , Proteínas Proto-Oncogénicas c-akt/metabolismo , Quimiocina CCL5/metabolismo , Transducción de Señal/efectos de los fármacos , Ratas , Factor A de Crecimiento Endotelial Vascular/metabolismo , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/prevención & control , Úlcera Gástrica/patología , Úlcera Gástrica/metabolismo , Serotonina/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismoRESUMEN
Gastric ulcer is a common disease affecting pigs worldwide, with a prevalence reported as high as 93%. The cause of porcine gastric ulcer is multifactorial, with Helicobacter suis (H. suis) being considered as the primary pathogenic factor. To date, prevalence of H. suis resulting in porcine gastric ulcer in Taiwan has not been investigated. In this study, we collected 360 pig stomachs from the slaughterhouses. In addition, stomach tissues from the 88 diseased pigs submitted for necropsy were divided into symptomatic and asymptomatic groups. Gastric lesions were scored, and polymerase chain reaction was used to determine the occurrence of gastric ulcer and the prevalence of H. suis. The positive rate of H. suis in the samples from slaughtered pigs was 49.7%, and both infection of H. suis and the presence of gastric lesions were prone to occur in autumn. The positive rates of H. suis infection in the symptomatic and asymptomatic groups were 59.1% and 31.8%, respectively. Moreover, the proportion of the samples with gastroesophageal ulcer in the symptomatic group was 68.2%, predominantly observed in growing pigs. The incidence of the samples from the slaughterhouses with gastroesophageal erosion to ulceration revealed a significant difference between H. suis -infected and H. suis -uninfected pigs; however, there is no significant difference in the samples of diseased pigs. In conclusion, H. suis infection was associated with gastric ulcer in slaughtered pigs, but it was not the primary cause of gastroesophageal ulcer in diseased pigs with clinical symptoms.
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Infecciones por Helicobacter , Helicobacter heilmannii , Úlcera Gástrica , Enfermedades de los Porcinos , Animales , Taiwán/epidemiología , Enfermedades de los Porcinos/epidemiología , Enfermedades de los Porcinos/microbiología , Úlcera Gástrica/veterinaria , Úlcera Gástrica/epidemiología , Úlcera Gástrica/microbiología , Úlcera Gástrica/patología , Porcinos , Infecciones por Helicobacter/veterinaria , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/microbiología , Prevalencia , Helicobacter heilmannii/aislamiento & purificación , Mataderos , Reacción en Cadena de la Polimerasa/veterinariaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Zingiberis rhizoma recens-/wine-/euodiae fructus-processed Coptidis Rhizoma (CR, zCR/wCR/eCR) are the commonly used processed products of CR in clinic. After being processed with different excipients, the efficacy of CR will change accordingly. I.e., wCR could resolve excessive heat of the upper energizer, zCR could eliminate gastric heat and harmonize the stomach, eCR could smooth the liver and harmonize the stomach. However, the underlying mechanisms were still unclear. AIM OF THE STUDY: To further verify the differential efficacy of the three processed CR products and compare the mechanisms on gastric ulcer. MATERIAL AND METHODS: First, a GU model, whose onset is closely related to the heat in stomach and the disharmony between liver and stomach, was established, and the therapeutic effects of zCR/wCR/eCR/CR were evaluated by pathologic observation and measurement of cytokine levels. Second, metabolomics analysis and network pharmacology were conducted to reveal the differential intervening mechanism of zCR/eCR on GU. Third, the predicted mechanisms from metabolomics analysis and network pharmacology were validated using western blotting, flow cytometry and immunofluorescence. RESULTS: zCR/wCR/eCR/CR could alleviate the pathologic damage to varying degrees. In metabolomics research, fewer metabolic pathways were enriched in serum samples, and most of them were also present in the results of gastric tissue samples. The gastroprotective, anti-inflammatory, antioxidant, and anti-apoptotic effects of zCR/wCR/eCR/CR might be due to their interference on histidine, arachidonic acid, and glycerophospholipids metabolism. Quantitative results indicated that zCR/eCR had a better therapeutic effect than wCR/CR in treating GU. A comprehensive analysis of metabolomics and network pharmacology revealed that zCR and eCR exerted anti-GU effects via intervening in five core targets, including AKT, TNF, IL6, IL1B and PPARG. In the validation experiment, zCR/eCR could significantly reverse the abnormal expression of proteins related to apoptosis, inflammation, oxidative stress, gastric function, as well as the PI3K/AKT signaling pathways. CONCLUSION: zCR and eCR could offer gastroprotective benefits by resisting inflammation and apoptosis, inhibiting gastric-acid secretion, as well as strengthening gastric mucosal defense and antioxidant capacity. Integrating network pharmacology and metabolomics analysis could reveal the acting mechanism of drugs and promote the development of medications to counteract GU.
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Medicamentos Herbarios Chinos , Metabolómica , Farmacología en Red , Ratas Sprague-Dawley , Úlcera Gástrica , Animales , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/patología , Úlcera Gástrica/metabolismo , Medicamentos Herbarios Chinos/farmacología , Masculino , Ratas , Evodia/química , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Mucosa Gástrica/metabolismo , Coptis chinensis , Modelos Animales de Enfermedad , Antiulcerosos/farmacología , Antiulcerosos/aislamiento & purificación , Citocinas/metabolismo , Citocinas/sangreRESUMEN
The present study was designed to assess Tradescantia spathacea's antidiabetic ability, as well as the antiulcer activity of the entire plant extract. The diabetic condition was evaluated using Streptozotocin's oral glucose tolerance test, diabetes-alloxan and diabetes-models. Antiulcer activities were observed in rats where gastric ulcers were either caused by oral administration of ethanol, or pyloric ligation. Standards include ranitidine, glibenclamide and sucralfate. In all models, the blood glucose levels of animals treated with the test extract were found to be significantly lower compared to diabetic care. Similarly, in all models, the ulcer index in the animals treated with the test extract was found to be significantly lower relative to the animals under vehicle supervision. Our findings say T. Spathacea extract has essential anti-diabetic properties, as well as antiulcer properties.
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Antiulcerosos , Glucemia , Diabetes Mellitus Experimental , Hipoglucemiantes , Extractos Vegetales , Ratas Wistar , Úlcera Gástrica , Animales , Hipoglucemiantes/farmacología , Hipoglucemiantes/aislamiento & purificación , Extractos Vegetales/farmacología , Extractos Vegetales/aislamiento & purificación , Antiulcerosos/farmacología , Antiulcerosos/aislamiento & purificación , Diabetes Mellitus Experimental/tratamiento farmacológico , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/prevención & control , Úlcera Gástrica/patología , Úlcera Gástrica/inducido químicamente , Masculino , Ratas , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Metanol/química , Prueba de Tolerancia a la Glucosa , Solventes/química , FitoterapiaRESUMEN
The purpose of this study was to evaluate the effects of syringic acid, an anti-oxidant, on indomethacin induced gastric ulcers in rats. Experimental groups were control, ulcer, ulcer treated with 20 mg/kg esomeprazole (a proton pump inhibitor that reduces acid secretion), and ulcer treated with 100 mg/kg syringic acid. Rats were pretreated with esomeprazole or syringic acid two weeks before ulcer induction. Our histopathological observations showed that either syringic acid or esomeprazole attenuated the severity of gastric mucosal damage. Moreover, syringic acid and esomeprazole pretreatments alleviated indomethacin-induced damage by regulating oxidative stress, inflammatory response, the level of transforming growth factor-ß (TGF-ß), expressions of COX and prostaglandin E2, cell proliferation, apoptosis and regulation of the NF-κB signaling pathway. We conclude that either esomeprazole or syringic acid administration protected the gastric mucosa from harmful effects of indomethacin. Syringic acid might, therefore be a potential therapeutic agent for preventing and treating indomethacin-induced gastric damage.
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Apoptosis , Ácido Gálico , Indometacina , Inflamación , Estrés Oxidativo , Úlcera Gástrica , Animales , Indometacina/farmacología , Indometacina/toxicidad , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/patología , Estrés Oxidativo/efectos de los fármacos , Apoptosis/efectos de los fármacos , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Masculino , Ácido Gálico/análogos & derivados , Ácido Gálico/farmacología , Ratas , Ratas Sprague-Dawley , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Esomeprazol/farmacologíaRESUMEN
BACKGROUND: There are patents available related to fermented food and beverages which enhance to human health. Citrus limetta (Mosambi) has a high content of flavonoids and exhibits antioxidant activity, which could stimulate the digestive system and be useful for gastroprotective activity. It supports digestion by neutralizing the acidic digestive juices and reducing gastric acidity. OBJECTIVE: This study explored the potential of using waste peel extract from Citrus limetta to prevent ulcers. The study specifically sought to assess the anti-ulcer properties of fermented and non-fermented extracts and compare them. Further, the study looked at the potential benefits of treating or preventing ulcers with Citrus limetta waste peels and whether fermentation affected the efficacy of the treatment. METHODS: Thirty female Wistar albino rats were equally distributed into five different groups. Group 1 received distilled water (20 ml/kg/b.w); Group 2 received indomethacin (mg/kg/b.w); Group 3 received omeprazole (20 mg/kg/b.w); Group 4 received aqueous extract of Mosambi peel (400 mg/kg/b.w) and Group 5 received fermented product of extract of Mosambi peel (400 mg/kg/b.w). RESULTS: Findings explored that, compared to non-fermented citrus fruit juice, biofermented exhibited less gastric volume (1.58 ± 0.10 ml vs. 1.8 ± 0.14 ml), reduced MDA levels (355.23 ± 100.70 µmol/mg protein vs. 454.49 ± 155.88 µmol/mg protein), and low ulcer index (0.49 ± 0.07 vs. 0.72 ± 0.14). CONCLUSION: The results suggest that the bio-fermented product of Citrus limetta peel has better anti-ulcer potential against peptic ulcer induced by indomethacin in Wistar albino rats compared to non-fermented.