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SARS-CoV-2 is causing a pandemic of COVID-19, with high infectivity and significant mortality 1 . Currently, therapeutic options for COVID-19 are limited. Historically, metal compounds have found use as antimicrobial agents, but their antiviral activities have rarely been explored. Here, we test a set of metallodrugs and related compounds, and identify ranitidine bismuth citrate, a commonly used drug for the treatment of Helicobacter pylori infection, as a potent anti-SARS-CoV-2 agent, both in vitro and in vivo. Ranitidine bismuth citrate exhibited low cytotoxicity and protected SARS-CoV-2-infected cells with a high selectivity index of 975. Importantly, ranitidine bismuth citrate suppressed SARS-CoV-2 replication, leading to decreased viral loads in both upper and lower respiratory tracts, and relieved virus-associated pneumonia in a golden Syrian hamster model. In vitro studies showed that ranitidine bismuth citrate and its related compounds exhibited inhibition towards both the ATPase (IC 50  = 0.69 µM) and DNA-unwinding (IC 50  = 0.70 µM) activities of the SARS-CoV-2 helicase via an irreversible displacement of zinc( ii ) ions from the enzyme by bismuth( iii ) ions. Our findings highlight viral helicase as a druggable target and the clinical potential of bismuth( iii ) drugs or other metallodrugs for the treatment of SARS-CoV-2 infection. Drug used to treat Helicobacter pylori infection reduces SARS-CoV-2 viral loads in lungs and alleviates virus-associated pneumonia in a golden Syrian hamster model.

The use of inhibitors of gastric acid secretion (IGAS), especially proton pump inhibitors (PPI), has been associated with increased cardiovascular risk. While the mechanisms involved are not known, there is evidence supporting increased oxidative stress, a major activator of matrix metalloproteinases (MMP), as an important player in such effect. However, there is no study showing whether other IGAS such as histamine H2-receptor blockers (H2RB) cause similar effects. This study aimed at examining whether treatment with the H2RB ranitidine promotes oxidative stress resulting in vascular MMP activation and corresponding functional and structural alterations in the vasculature, as compared with those found with the PPI omeprazole. Male Wistar rats were treated (4 weeks) with vehicle (2% tween 20), omeprazole (10 mg/Kg/day; i.p.) or ranitidine (100 mg/Kg/day; gavage). Then the aorta was collected to perform functional, biochemical, and morphometric analysis. Both ranitidine and omeprazole increased gastric pH and oxidative stress assessed in situ with the fluorescent dye dihydroethidium (DHE) and with lucigenin chemiluminescence assay. Both IGAS augmented vascular activated MMP-2. These findings were associated with aortic remodeling (increased media/lumen ratio and number of cells/μm2). Both IGAS also impaired the endothelium-dependent relaxation induced by acetylcholine (isolated aortic ring preparation). This study provides evidence that the H2RB ranitidine induces vascular dysfunction, redox alterations, and remodeling similar to those found with the PPI omeprazole. These findings strongly suggest that IGAS increase oxidative stress and matrix metalloproteinase-2 activity leading to vascular remodeling, which helps to explain the increased cardiovascular risk associated with the use of those drugs.

Objective. The present study was aimed at investigating the possible antiulcer activities of some natural phytochemicals Aloe perryi leaf extract (APLE) and flower extract (APFE) in addition to the date palm seed extract (DPSE) and the oily samples of DPSE in a pylorus ligation-induced ulcer model using ranitidine as a standard antiulcer drug. Background. Peptic ulcer is a prevalent gastrointestinal disorder due to hypersecretion of gastric acid. It affects four million people worldwide, and 2-10% of these ulcers are perforated and cause bleeding. This increases the risk of morbidity and mortality. So we aimed to introduce a primary study alternatively safe method for treating peptic ulcer. Materials and Methods. Forty-two Wistar Albino rats of either sex were randomly divided into seven groups (6/each). The pylorus ligation was done to induce ulcer in pretreated albino rats. The antiulcer activities of extracts were estimated at different dose levels (250 and 500 mg/kg) using ranitidine as a standard drug (50 mg/kg). Gastric volume, pH, and total and free acidity as well as ulcer index and percentage of ulcer inhibition were measured to elucidate the antiulcerogenic effects. Histological examination of gastric ulcer was also performed. Statistical analysis for the results was done where P<0.05 was considered statistically significant. Results. Pylorus ligation for 6 h in control rats resulted in gastric ulcer which was indicated by the accumulation of gastric secretion and increased total acidity and decreased pH. The pretreatment of rats with APLE, APFE, and DPSE in addition to the oily samples of DPSE significantly inhibited the ulcers induced by pylorus ligation. These effects were attributed to significant reductions in total and free acidity, ulcer index, and gastric volume while there is a marked decrease in gastric pH (the antisecretory) as well as mucosal strengthening properties of these phytochemicals. Conclusion. These findings give these extracts the potential to be a promising tool for the management of gastric ulcer after performing further clinical and experimental studies. Our study demonstrated the promising antiulcer activity of extracts and oils in pyloric ligation-induced gastric ulcer. To the best of our knowledge, this is the first study to explore the antiulcer activity of these extracts; however, further investigations may be recommended for full details about this antiulcerogenic capacity.

BackgroundThe accidental ingestion of the third larval stage of Anisakis can cause acute clinical symptoms, which are relieved via extraction of the larvae. Although this is a highly effective technique, it can only be practiced when the larvae are found in accessible areas of the gastrointestinal tract, and therefore instead the condition has often been treated using various different drugs.AimsThis study evaluates the effectiveness of gastric acid secretion inhibitors (omeprazole and ranitidine), gastric mucosal protectants (sucralfate) and anthelmintics (mebendazole and flubendazole) in treating anisakiasis in Wistar rats.MethodsRats were infected with Anisakis-type I larvae and administered the drugs via a gastric probe. Data were recorded regarding the number of live and dead larvae, their location both within the animal and in its feces, and the presence of gastrointestinal lesions. Additionally, gastric pH was measured and histology performed.ResultsWhile rats in all experimental groups exhibited lesions; those treated with ranitidine and mebendazole showed significantly fewer lesions (50% and 35% of rats exhibited lesions, respectively). Histological examination of the gastric lesions revealed infection-induced changes, but no significant differences were observed between the treated and untreated rats.ConclusionsMebendazole was found to be most efficacious in preventing gastrointestinal lesions, followed by ranitidine, which was the most effective antacid of those studied. Both these drugs could thus be considered as part of the conservative management of anisakiasis.

This study aimed to investigate the antioxidant and protective effect of E. persicus leaf hydroalcoholic extract (EPE) in preventing gastric ulcers induced by ethanol in rats. Wistar rats weighing 180–220 g were randomly divided into five groups. These groups included negative control (normal) group, positive control (ethanolic) group, comparative control (ranitidine recipient) group, group recipient the dose of 250 mg/kg plant extract, and group recipient the dose of 500 mg/kg plant extract. One hour after gavage of the drug and extract, the gastric ulcer was induced by feeding 1 ml of 96% ethanol to each animal except the rats of the negative control group. After one hour, the rats were killed, and their stomachs were separated. Then, the gastric Ulcer index (UI), pH, oxidative stress parameters, and histopathological changes in the stomach of all groups were measured. Pre-treatment of ethanol-induced rats with the EPE reduced ( P  < 0.05) the ulcer index and gastric juice pH, compared to ethanolic group rats. Furthermore, pre-treatment with EPE at a dose-dependent manner, alleviated the gastric oxidative stress injury in rats through increase the activity of CAT, tissue NO · and GSH levels. EPE also was able to decrease the levels of ROS, MDA, PCO and serum NO · . According to the results, it can be concluded that pre-treatment with EPE prevents the formation of gastric ulcers caused by ethanol, which can be attributed to the antioxidant activity of plant polyphenols compounds.

The purpose of the study was to develop a novel, directly compressible, co-processed excipient capable of providing a controlled-release drug system for the pharmaceutical industry. A co-processed powder was formed by adsorption of solid lipid nanoparticles (SLN) as a controlled-release film onto a functional excipient, in this case, dicalcium phosphate dihydrate (DPD), for direct compression (Di-Tab®). The co-processed excipient has advantages: easy to implement; solvent-free; industrial scaling-up; good rheological and compressibility properties; and the capability to form an inert platform. Six different batches of Di-Tab®:SLN weight ratios were prepared (4:0.6, 3:0.6, 2:0.6, 1:0.6, 0.5:0.6, and 0.25:0.6). BCS class III ranitidine hydrochloride was selected as a drug model to evaluate the mixture’s controlled-release capabilities. The co-processed excipients were characterized in terms of powder rheology and dissolution rate. The best Di-Tab®:SLN ratio proved to be 2:0.6, as it showed high functionality with good flow and compressibility properties (Carr Index = 16 ± 1, Hausner Index = 1.19 ± 0.04). This ratio could control release for up to 8 h, so it fits the ideal profile calculated based on biopharmaceutical data. The compressed systems obtained using this powder mixture behave as a matrix platform in which Fickian diffusion governs the release. The Higuchi model can explain their behavior.

Gastric ulcers are caused by an imbalance between aggressive and defensive factors. The green synthesis of silver nanoparticles is becoming a new and promising method in the treatment of gastrointestinal ulcers. This study was conducted to investigate the protective and antioxidant effects of silver nanoparticles synthesized from Quercus brantii extract (NSQBE) on gastric damage induced by alcohol in rats. In this study, silver nanoparticles were produced by the green synthesis method using oak extract. The structure and morphology of nanoparticles were confirmed by various techniques such as UV–Vis spectroscopy, fourier transforms infrared spectrometer (FTIR), scanning electron microscope (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), energy-dispersive X-ray analysis (EDX), and dynamic light scattering )DLS(. For the animal studies, 30 male Wistar rats weighing 200 ± 20 g were randomly selected and divided into five groups (the normal, ethanolic, NSQBE treatment (received doses of 20 and 5 mg/kg), and standard (received a dose of 50 mg/kg of ranitidine) groups. After the rats were euthanized, their stomach was removed. A part of the stomach tissue of rats was used for histopathological studies, and the other part was used to study biochemical parameters such as the level of reactive oxygen species (ROS), protein carbonyl oxidation (PCO), malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD) and reduced glutathione (GSH) as well as nitric oxide (NO). Our results showed that in the ethanol group, the levels of ROS, MDA, PCO, and serum NO were higher than in the normal group. In addition, reduced GSH, CAT, SOD, tissue NO, gastric mucus, and antioxidant potential were decreased. In rats pretreated with NSQBE and ranitidine, the levels of ROS, MDA, PCO, and serum NO decreased, and the levels of GSH, CAT, SOD, tissue NO, gastric mucus, and antioxidant potential were increased in comparison to the ethanol group. The results of this study showed that silver nanoparticles synthesized using Quercus brantii are a promising approach for the treatment of gastric ulcers.

Aims: Organophosphates (OPCs), useful agents as pesticides, also represent a serious health hazard. Standard therapy with atropine and established oxime-type enzyme reactivators is unsatisfactory. Experimental data indicate that superior therapeutic results can be obtained when reversible cholinesterase inhibitors are administered before OPC exposure. Comparing the protective efficacy of five such cholinesterase inhibitors (physostigmine, pyridostigmine, ranitidine, tacrine, or K-27), we observed best protection for the experimental oxime K-27. The present study was undertaken in order to determine if additional administration of K-27 immediately after OPC (paraoxon) exposure can improve the outcome. Methods: Therapeutic efficacy was assessed in rats by determining the relative risk of death (RR) by Cox survival analysis over a period of 48 h. Animals that received only pretreatment and paraoxon were compared with those that had received pretreatment and paraoxon followed by K-27 immediately after paraoxon exposure. Results: Best protection from paraoxon-induced mortality was observed after pretreatment with physostigmine (RR = 0.30) and K-27 (RR = 0.34). Both substances were significantly more efficacious than tacrine (RR = 0.67), ranitidine (RR = 0.72), and pyridostigmine (RR = 0.76), which were less efficacious but still significantly reduced the RR compared to the no-treatment group (paraoxon only). Additional administration of K-27 immediately after paraoxon exposure (posttreatment) did not further reduce mortality. Statistical analysis between pretreatment before paraoxon exposure alone and pretreatment plus K-27 posttreatment did not show any significant difference for any of the pretreatment regimens. Conclusions: Best outcome is achieved if physostigmine or K-27 are administered prophylactically before exposure to sublethal paraoxon dosages. Therapeutic outcome is not further improved by additional oxime therapy immediately thereafter.

Background Gastric acid suppressants frequently are used in cats with acid‐related gastric disorders. However, it is not known if these drugs effectively increase intragastric pH in cats. Objectives To examine the effects of PO administered ranitidine and omeprazole on intragastric pH in cats and to compare the efficacy of once‐daily versus twice‐daily dosage regimens for omeprazole. Animals Eight domestic shorthair cats. Methods Using a randomized 4‐way cross‐over design, cats were given enteric‐coated omeprazole granules (1.1–1.3 mg/kg q24h and q12h), ranitidine (1.5–2.3 mg/kg q12h), and placebo. Intragastric pH was monitored continuously for 96 hours using the Bravo™ system, starting on day 4 of treatment, followed by a median washout period of 12 days. Mean percentage of time pH was ≥3 and ≥4 was compared among groups using repeated measures ANOVA. Results Mean ± SD percentage of time intragastric pH was ≥3 and ≥4 was 67.0 ± 24.0% and 54.6 ± 26.4% for twice‐daily omeprazole, 24.4 ± 22.8% and 16.8 ± 19.3% for once‐daily omeprazole, 16.5 ± 9.0% and 9.6 ± 5.9% for ranitidine, and 9.4 ± 8.0% and 7.0 ± 6.6% for placebo administration. Twice‐daily omeprazole treatment significantly increased intragastric pH, whereas pH after once‐daily omeprazole and ranitidine treatments did not differ from that of placebo‐treated cats. Conclusion and Clinical Importance Only twice‐daily PO administered omeprazole significantly suppressed gastric acidity in healthy cats, whereas once‐daily omeprazole and standard dosages of ranitidine were not effective acid suppressants in cats.

ABSTRACT Gastric ulcer (GU) is the most common health concern that occurs due to an imbalance between gastric protective mucosal and aggressive factors. Ethanol‐induced GU in animal models resembles the pathophysiology of human ulcers. Natural products with fewer side effects are highly requested to attenuate their GU effects. The present study was conducted to investigate the potential protective effects of donkey milk against ethanol‐induced GU in rats. The male Wistar were divided into four groups, including normal control (distilled water), donkey milk (1 cm3/animal) and ranitidine (200 mg/kg). Donkey milk and ranitidine were given to rats orally daily for 10 consecutive days before induction of ulcer by ethanol. After 24 h of fasting, GU was induced by oral administration of ethanol. After an hour, the rats were sacrificed, and gastric samples were taken for pathologic analysis, malondialdehyde (MDA) and glutathione (GSH) assessments. The results showed that the severity of ethanol‐induced gastric damage was significantly reduced by donkey's milk pretreatment and then ranitidine. Reduction of ulcer score and MDA level, and also increasing GSH in the gastric tissue in comparison with other groups supports our results. This study described the gastroprotective and antioxidative effects of donkey milk that were determined with ulcer inhibition percentage. We investigated the gastroprotective activity of donkey milk on ethanol‐induced gastric ulcer in rat. Results of our study indicated donkey milk significantly decreased gastric ulcer index and malondialdehyde (MDA) level in the gastric tissue. The present study suggests that one of the anti‐ulcerogenic efficacies of donkey milk may be related to its antioxidative properties. Donkey milk may exert its protective property by inhibiting lipid peroxidation marker (MDA). However, the precise mechanism for this action remains to be elucidated.