Gastritis, peptic ulcers, acid reflux, and other gastrointestinal problems may be effectively managed and prevented with the use of gastroprotective medicines. To protect the stomach mucosa against pepsin, gastric acid, and other potentially damaging substances, these medications are useful. The hunt for potent gastroprotective compounds has heated up in response to the rising global incidence of gastrointestinal illnesses. A perovskite-type oxide, Neodymium Manganite (NdMnO3) “has attracted a lot of attention because of its unusual electrical, structural, and magnetic characteristics. Recent studies have started to investigate the possible biological uses of NdMnO3, which has traditionally been researched for its uses in electronics” and catalysis. Its gastroprotective action is one area that shows promise (Wallace, 2008). The “capacity of NdMnO3 to regulate oxidative stress, inflammation, and other biochemical processes that lead to stomach mucosal injury is the reason for its gastroprotective possibilities. An important factor in the development of a number of gastrointestinal” diseases is oxidative stress, which is defined as an imbalance between the generation of reactive oxygen species (ROS) and the antioxidant defence systems. Potentially reducing oxidative damage to the stomach mucosa, NdMnO3 scavenges ROS and enhances antioxidant enzyme activity. In addition, by blocking important inflammatory mediators including prostaglandins and cytokines, NdMnO3 may display anti-inflammatory behaviours. Suppressing inflammatory pathways may help greatly to mucosal protection and repair, which is important since inflammation is a prevalent underlying component in many gastrointestinal diseases (Toma et al., 2005). The objective of this research is to examine, by means of a battery of in vitro and in vivo tests, the gastroprotective action of NdMnO3. This study aims to provide light on the processes by which NdMnO3 provides its protective properties. The ultimate goal is to create new therapeutic approaches for gastrointestinal disorders, both to cure and prevent them (Szabo, 1985).

METHODOLOGY

Experimental Details

We obtained 23 male Wistar rats from the University's animal facility; they were 8 weeks old and weighed 180-220 g. There was no deviation from the “1985 National Institutes of Health Guide for the Care and Use of Laboratory Animals in any of the animal operations. Official Mexican regulations for the use and care of laboratory animals (no. NOM-062-ZOO-1999) dictated the housing, handling, and overall treatment of the animals. The animal research was examined and authorised by an internal bioethical” council. All of the animals were maintained in controlled environments with regulated temperatures (22°C), light cycles (12 hours of light and 12 hours of darkness), and relative humidity (46-50%). Water and rat food were available to the animals at all times. Each one was kept in its own plastic cage. The rats were allowed to drink water freely before the trial began, but they were fasted for 24 hours beforehand (Sandor et al., 2005).

Drugs

This antiulcer evaluation made use of NdMnO3 nanoparticles.

Animal experiment to assess anti-ulcer activity

Gastric ulcer induction was carried out in accordance with the procedure detailed by Konturek et al., “Lewis and Shaw, and Narayan et al. Each of the three groups of rats consisted of six individuals chosen at random. A saline solution was given to the third group, while the first two groups were given acetylsalicylic acid (ASA) via intragastric gavage at a dosage of 150 mg/kg body weight to develop gastric ulcers. The second group was given 400 mg/kg body weight of NdMnO3 mixed with regular rat chow right after induction, whereas the other groups were given the same thing without NdMnO3. This dosage was reported in earlier experiments with a small number of animals to have anti-ulcerative effects. The animals were fed and kept in their own cages for five days. Sodium pentobarbital (120 mg/kg) was injected intraperitoneally the next day to euthanize all of the animals”. The guts of the animals were painstakingly removed during the dissection process. The stomachs were cleaned with PBS after an incision was made along the larger curvature. A microscopic examination of mucosal lesions was performed.

Ulcerative index (UI) and protective effect

The following formula was used to calculate the UI, which takes into consideration the degree of damage to the gastric mucosa: “UI= [1× (number of lesions of ≝1 mm) + 2× (number of lesions of 1-2 mm) + 3× (number of lesions >2 mm)]/10”.

To determine the percentage of ulcer prevention, the total score was split among the 10 ulcer index items. To calculate ulcer protection as a percentage, subtract the ulcer-induced group from the ulcer-treated group and then divide by two.multiply by 100, divided by the group that developed ulcers due to UI.

Lipid peroxidation

The gastric mucosal “tissues were homogenised using a Tissue-Tearor (BioSpec Products Inc.) after being put in a 20 mM Tris-HCl buffer (pH 7.4) at 4°C. The concentration of the tissues was 100 mg/ml. The mixtures were spun in a centrifuge at 2,000 × g for 10 minutes at 4°C. After collecting the liquid portion, it was kept at 4°C until needed. Using the Lipid Hydroperoxide Assay kit (Bioquochem SL), the quantity of malondialdehyde (MDA) and 4-hydroxynonenal (HNE) was used to estimate the degree of lipid peroxidation. Briefly, a 1:3 combination of acetonitrile and methanol was supplemented with 200 µl of the supernatant and 650 µl of 10.3 nM N-methyl-2-phenylindole. Afterwards, 150 µl of methanesulfonic acid was added and the mixture was left to incubate at 40°C for 40 minutes afterwards. Afterwards, the tubes were spun at 5,000 × g for 5 minutes at room” temperature. At last, the “absorbance was measured at 586 nm after 200 µl of the supernatant was collected. At the same time, a standard calibration curve was created to determine the concentration” of the sample (Pohle, 2003).

Acute toxicity

It was determined to administer” 400 mg/kg NdMnO3 all at once to prove that this dosage is safe, in accordance with the OECD 425 recommendations, which provide that a limit test (a maximum fixed dose) may be conducted with five animals using 2,000 mg/kg NdMnO3 as a starting point. Fifteen rats were given 400 mg/kg of NdMnO3 via intragastric” gavage. The “animals were monitored for a week to identify any symptoms of toxicity and for an extra week to identify any indicators of delayed toxicity. Clinical symptoms, body mass index, and mortality rates were documented. Separate blood samples were taken from the tail vein 14 days after NdMnO3 injection and kept at −80°C until biochemical parameter examination. The Jendsrassik and Grof technique was used to assess bilirubin, while the Reitman and Frankel method was used to measure the activities of alanine transaminase (ALT) and aspartate transaminase (AST). The albumin concentration was determined using the Doumas et al. technique, and the alkaline phosphatase (ALP) activity was measured using the” Bessey et al. method.

Statistical analysis

Mean ± “standard error of the mean is how values are presented. The groups were compared using one-way analysis of variance and Tukey's post hoc test to find any statistically significant differences. A significant level of P<0.05 was deemed” to signify statistical importance. A statistical analysis was conducted using the programme SigmaStat 8.0.

RESULT

Analysis of gastric lesions

The glandular areas of the stomach showed gastric mucosal lesions in the ulcer-induced group, measuring more than 2 mm in diameter. The lesions on the mucosa seemed to be elongated bands of black and dark red. Rats given NdMnO3 after developing ASA-induced stomach ulcers showed a gastroprotective effect, which is noteworthy. The non-induced group also had mucosal gastric lesions that were comparable in severity, and their lesions were less than 1 mm in diameter.

Anti-ulcerative effects of NdMnO₃

In the “group that developed ulcers due to ASA administration, severe stomach lesions with an ulcer index value of 9.65±0.89 were observed. The rats in the ulcer-induced group that were given NdMnO3 powder showed a much less severe and fewer gastrointestinal lesions, with a UI of 4.52±0.14. Fig. 2 shows that, surprisingly, this group's UI value was much lower than the non-induced” group's (UI=5.04±0.30).

DISCUSSION

Research on medicinal plants is crucial for finding new medicines to treat gastrointestinal problems. Here, we looked at rat studies that examined the anti-ulcerative properties of NdMnO3 against stomach ulcers caused by ASA. Research on gastroprotective effects, gastrointestinal irritation, gastric haemorrhage, lipid peroxidation, carbonylated protein content, and elevations in gastric myeloperoxidase activity has been conducted using the rat model of ASA-induced gastric ulcers. Animals with ASA-induced stomach ulcers showed a gastroprotective effect of 53.16±2.60% after ingesting NdMnO3, which was significantly lower in the UI group compared to the ASA-induced ulcer group. The findings from the research conducted by Sánchez-Mendoza et al., which included the administration of a hexane extract from the leaves of NdMnO3 to rats suffering from ethanol-induced stomach ulcers, are in line with the outcomes seen here. The primary active ingredients of Eupatorium plants are secondary metabolites, which include terpenes, flavonoids”, and alkaloids. These compounds have been shown to have anti-ulcer properties.

Increased lipid peroxidation, caused by ASA-induced reactive oxygen species generation, damages cell membrane lipids. “Important hazardous consequences of lipid peroxidation, MDA and HNE aldehydes are used as markers of tissue injury. These findings regarding the potential antioxidant activity were similar to those reported by Tuluce et al. (2011) and Krishnan et al. (2011), respectively, using 50% aqueous-ethanolic small centaury in an acute gastric ulcer model and methanolic fractions of Eupatorium triplinerve on a model of ulcerative colitis caused by acetic acid in mice. Rats given NdMnO3 had substantially lower levels of MDA and HNE in gastric mucosal tissues compared to those in the ASA-induced ulcer group”. It is possible that the feed intake of the rats soon after ASA treatment lowered the capacity of ASA to cause ulcers, even if these data imply that NdMnO3 displayed gastroprotective effects at the level used. Despite the widespread use of many traditional medicines for illness prevention and treatment, the safety of these plants is still up for debate since they contain bioactive components that might have negative side effects. This is why it's crucial to assess the effectiveness and safety of traditional and alternative medicine, since their use is on the rise throughout the globe. After administering 400 mg/kg of NdMnO3 powder to assess its acute toxicity, all animals showed signs of tolerance “and showed no signs of death or toxicity. One way that chemicals and pharmaceuticals might manifest their harmful effects is via changes in body weight. In this study, researchers could not find any correlation between participants' food consumption and body weight. Serum bilirubin, AST, ALT, ALP, and gamma-glutamyl transferase levels, as well as those of other biochemical markers used to assess liver function, were not substantially different from those in the non-induced group. Creatinine, urea, and albumin are renal indicators that showed no difference between the two groups. Considering that no harmful side effects were noted, it can be concluded that consuming NdMnO3 when administered at a specific dosage is safe. Additional research is needed to evaluate NdMnO3 in comparison to other medications used to treat ulcers. Ultimately, this research found that NdMnO3 has gastroprotective” and anti-ulcerative properties in rats with ASA-induced stomach ulcers, which might lead to its usage in gastric ulcer prevention. Furthermore, no signs of liver or kidney damage were found following acute oral administration of NdMnO3, so the ingestion of this metal was deemed pharmacologically safe.

CONCLUSION

Ultimately, the results show that NdMnO3 has the makings of a great agent for the treatment and prevention of stomach ulcers, according to the research on its gastroprotective action. Based on the results of the experiments, NdMnO3 has a number of gastroprotective properties, including increasing gastric mucus production, decreasing stomach acidity, and speeding up the healing process of gastric mucosal injury. The compound's antioxidant characteristics further help explain its protective benefits by reducing oxidative stress, an important player in stomach ulcer pathophysiology. The safety profile and therapeutic effectiveness of NdMnO3 in clinical settings, as well as the mechanisms behind its gastroprotective properties, need further investigation. To further comprehend its possible uses in gastroenterology, we must investigate its interactions with other gastroprotective drugs and evaluate its long-term effects. As a whole, NdMnO3 is an exciting new possibility for better gastric ulcer disease management via the creation of gastroprotective treatments.

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