Antiulcerogenic Activity of Vitamin E on Gastric Ulcers produced by Indomethacin

Objective: To study the morphological and histological effects of vitamin E on gastric lesions produced by indomethacin.Materials and Methods: This was an animal interventional study, 48 adult healthy albino mice were selected and were split into four groups A, B, C and D. Number of animals in each group was 12. Group A was categorized as control. Evion 400mg/kg was administered to Group B. Indocid 25mg/kg was given to group C. Indocid and Evion both (25mg/kg &400 mg/kg respectively) were administered to Group D. In all group, six animals were selected and treated for three days and rest for eight days with calculated doses of drugs. Mice were sacrificed and dissection was done 24 hours after the last dose. The stomach was identified, washed, and observed under dissecting microscope to study the number and shape of ulcers. The dimension of ulcers was measured under a compound microscope.Results: No ulcers were seen in groups A and B. 35 and 10 ulcers were observed in groups C and D respectively. The mean number of ulcers in groups C and D was statistically significant (p-value=0.000). In comparison to group D, Pindot, linear, Irregular, and punched-out ulcers were more prevalent in group C and were statistically significant (p-value < 0.05). The mean linear dimension of ulcers in group C was much greater than in group D. The mean dimension of ulcers in group C1 and C2 was 262.50µm and 232.5µm respectively. Whereas in group D1 and D2 given both Indocid and vitamin E the dimensions were 56.5µm and 50µm.Conclusion: Vitamin E has an anti-ulcerogenic effect on stomach mucosa by reducing the number and dimension of ulcers.

ANTIULCEROGENIC EFFECT OF CRYOPRESERVED PLACENTA EXTRACT AND THE EFFECT OF LOW TEMPERATURES ON THE DIGESTIVE TRACT INJURED BY DICLOFENAC SODIUM IN THE EXPERIMENT

Today, the ulcerogenic effect of nonsteroidal anti-inflammatory drugs is a key factor that significantly limits their clinical use and is a serious medical and social problem, as these drugs are among the most commonly used drugs – they are used annually by about 5­–7% of the world's population. The aim is to characterize the antiulcerogenic effect of cryopreserved placenta extract and its application against the background of low temperatures in the model of diclofenac sodium-induced ulcerogenesis in rats according to macroscopic studies of the proximal and distal digestive tract. The study was performed on 42 male rats weighing 200–220 g. Acute diclofenac sodium-induced gastrointestinal damage was replicated by a single intragastric administration of diclofenac sodium to rats at a dose of 50 mg/kg. Euthanasia of animals was performed after 24 hours. The condition of the mucous membrane of the digestive tract was assessed on a scale and calculated integrated indicators – ulcer index and antiulcer activity. Cryocell-cryoextract of placenta was administered to rats intramuscularly at a dose of 0.16 ml/kg body weight. Cryoirrigation was performed once by local injection of liquid nitrogen vapor (temperature – 120˚C) for 10 s. It was found that diclofenac sodium at a dose of 50 mg/kg led to erosive-ulcerative damage to the gastric mucosa in 100% of rats, and the ulcer index was 3.9. The most pronounced leveling of the ulcerogenic effect of diclofenac sodium was observed against the combined preventive use of placental cryoextract and low temperature effect – the ulcer index was 12.6 times lower than that of rats with diclofenac sodium-induced ulcerogenesis without correction. Macroscopic evaluation of the distal gastrointestinal tract showed that the introduction of diclofenac sodium led to a statistically significant (p < 0.05) lesion of the mucous membrane of the small and large intestine in 42.9% of rats. According to the magnitude of antiulcer effect (%) in the model of diclofenac sodium-induced ulcerogenesis, the investigated prophylactic approaches for antiulcer activity have the following priority: action of low temperatures + cryoextract of placenta (96.7%) > cryoextract of placenta (92.1%) ~ esomeprazole (88.2%) > action of low temperatures (72.1%). No lesions of both the small and large intestine on the background of the introduction of placental cryoextract in the model of diclofenac sodium-associated ulcerogenesis were detected.

TOXICOLOGICAL EVALUATION OF INDOMETHACIN AS A RISK FACTOR FOR WORKERS’ HEALTH

Introduction. The toxicity of indomethacin was studied for its hygienic regulation. Material and methods. The toxic properties of indomethacin in the experiments on out-bred and linear mice, rats, Guinea pigs and rabbits contained in standard vivarium conditions and quarantined have been studied. In the experiments, various modes (single, repeated, chronic) and ways of exposure (intragastric, inhalation, epicutaneous) were modeled. The average lethal dose (LD50) of Indomethacin and the threshold of a single acute action (Limac) were determined; irritant effect on the skin and mucous membranes, cumulative and allergenic activity were revealed. In subacute and chronic intake to the body, the main target organs were determined on the based of the results of biochemical and hematological studies. Results. DL50 for male rats, females and male mice, when introduced into the stomach, were have been established to be 20, 15 and 25.6 mg/kg respectively. It refers to the substances of hazard class 2. DL50 in the intraperitoneal introduction for the rats accounted for 13.8 mg/kg, for Guinea pigs - 500 mg/kg. The clinical picture of acute poisoning in mice and rats was characterized by low mobility, decreasing breathing, ataxia, muscle relaxation, anorexia, diarrhea, ulceration with the perforation of the intestines, and the death on the 2-4th days after the poisoning. In the experiments on Guinea pigs, the ulcerogenic effect was not detected. Local irritant effect on the skin and mucous membranes of the eyes was not revealed. It has a marked skin-resorptive action causing ulcerogenic effect and the death of the animals after 6 applications. The introduction of verospiron to the rats in a dose of 25 mg/kg simultaneously with the application of indomethacin ointment on the skin prevented the ulcer development in the gastrointestinal tract and the death of the animals. No sensitizing effect was detected. It has an average cumulative ability: the cumulation coefficient amounted to 2.6. In a subacute experiment, there was a decrease in the body temperature and summation-threshold index, an increase in the vertical motor activity and a threshold of pain sensitivity. During the study of blood serum an increase in AcAt activity, a rise of chlorides in the blood serum and their decrease in the urine, and an increase in the number of erythrocytes and hemoglobin in peripheral blood were revealed. In the pathomorphological study, there was an increase in the coefficients of liver mass and ulceration of the stomach and intestines. The threshold of acute inhalation action accounted for 0.52 mg/m3 (by the reduction of the summation-threshold index and the content of sodium and chlorides in the urine). Conclusion. The maximum permissible concentration of indomethacin in the air of the working area was of 0.05 mg/m3 with the mark “special protection of the skin and eyes”, hazard class 1, aerosol.

Correction: Anti-ulcerogenic effect of KFP-H008 against ethanol-induced gastric ulcer via p38 MAPK/NF-κB pathway

Correction for ‘Anti-ulcerogenic effect of KFP-H008 against ethanol-induced gastric ulcer via p38 MAPK/NF-κB pathway’ by Mei Su et al., RSC Adv., 2017, 7, 49423–49435.

Synthesis and preliminary anti-inflammatory evaluation of xanthone derivatives

Xanthone derivatives of acetic, propionic and 2-methylpropionic acids were synthesized and assayed for their anti-inflammatory, analgesic and ulcerogenic activities. Compound 8 causes a dose-dependent diminution of paw edema (up to 61%) in the carrageenan model and at the highest tested dose reduces mechanical hyperalgesia in the Randall-Selitto test more effectively than the reference compound (~75% and ~32%, respectively). It shows high in vitro metabolic stability (Clint=12.5 μL/mg/min, t1/2=138.6 min) in the rat liver microsomes. None of the studied xanthone derivatives are ulcerogenic. The results of the present study suggest that compound 8 can be of interest in the future for the search for antinociceptive and antiedematous agents devoid of ulcerogenic effect.