Introduction. Non-steroidal anti-inflammatory drugs (NSAIDs) are ranked first among the world's effective anti-inflammatory and analgesic drugs with anticipated side effects. That is why the prevention of development of adverse reactions associated with NSAIDs, in particular, of those related to their ulcerogenicity, remains a serious global problem. Aims. To characterize the mechanisms of gastrocytoprotective activity of cryopreserved placenta in combined action of low temperatures and diclofenac sodium. Material and methods. The study was performed on 42 male rats weighing 200-220 g. Acute diclofenac sodium-induced gastropathy was reproduced by a single injection of the latter in rats at the dose of 50 mg/kg. The content of malonic dialdehyde, catalase activity, prostaglandin synthase activity and the content of nitrogen monoxide metabolites in homogenates of gastric mucosa were determined by spectrophotometric method. Results and discussion. The study showed that prophylactic administration of placental cryoextract in rats with diclofenac sodium-induced gastropathy is associated with increased activity of antioxidant system in gastric mucosa as demonstrated by an elevated catalase activity by 40.0% as compared with control rats. Modulation of antioxidant-prooxidant homeostasis is believed to be one of the principal mechanisms of gastrocytoprotective action in combined action of low temperatures and cryoextract of the placenta. This is shown by a statistically significant (p < 0.05) 2.2-fold increase of antioxidant-prooxidant index in the study group as compared with rats with diclofenac sodium-induced gastropathy. Administration of placental cryoextract was found to increase prostaglandin synthase activity in rats with diclofenac sodium-induced gastropathy by two times as compared with control rats, which would reduce iatrogenic prostaglandin deficiency in gastric mucosa. Also, the combined action of low temperatures and of placenta cryoextract was associated with a statistically significant (p < 0.05) increase in the level of metabolites of nitrogen monoxide (by 70.1%) as compared with rats with diclofenac sodium-induced gastropathy. Conclusions. Modulation of prooxidant-antioxidant homeostasis in gastric mucosa and increase in contents of nitrogen monoxide metabolites and prostaglandin synthase activity are the leading mechanisms of gastroprotective activity of cryopreserved placental extract in diclofenac sodium-induced gastropathy.
References
1.
Hladkykh FV, Chyzh MO, Manchenko AO, Belochkіna IV, Mikhailova IP. EFFECT OF CRYOPRESERVED PLACENTA EXTRACT ON SOME BIOCHEMICAL INDICES OF THERAPEUTIC EFFICIENCY AND TOXICITY OF DICLOFENAC SODIUM IN ADJUVANT-INDUCED EXPERIMENTAL ARTHRITIS. Pharmacy & Pharmacology. 9(4):278–93.
2.
Stepaniuk NG. Characteristics of the protective effect of quercetin and its water-soluble form of corvitin in a model of diclofenac-induced gastropathy. Georgian Med News. 2019;296:140–4.
3.
Iakovlieva LV, Titova AA. Research of medicinal products of the nsaid of the pharmaceutical market in Ukraine for the period 2014–2018. Farmatsevtychnyi zhurnal. (4):41–51.
4.
Hladkykh F, Chyzh M. MODULATION OF MELOXICAM-INDUCED CHANGES IN GASTROINTESTINAL AND MOTOR ACTIVITY OF THE STOMACH BY APPLYING PLACENTA CRYOEXTRACT. Proceedings of the Shevchenko Scientific Society Medical Sciences. 2021;64(1).
5.
Rybolovlev UR, Rybolovlev RS. Dosage of substances for mammals by constants of biological activity. Reports of the USSR Academy of Sciences. 1979;247(6):1513–6.
6.
Xie W, Huang X, Chen R, Chen R, Li T, Wu W, et al. <p>Esomeprazole alleviates the damage to stress ulcer in rats through not only its antisecretory effect but its antioxidant effect by inactivating the p38 MAPK and NF-κB signaling pathways</p> Drug Design, Development and Therapy. Volume 13:2969–84.
7.
Asakawa T, Matsushita S. Coloring conditions of thiobarbituric acid test for detecting lipid hydroperoxides. Lipids. 1980;15(3):137–40.
8.
Korolyuk MA, Ivanova LI, Mayorova IG. Method for determining catalase activity. Lab delo. 1988;1:16–9.
9.
Kamyshnikov VS. Handbook of clinical and biochemical research and laboratory diagnostics. 2009.
10.
Sumbaev Y, I.M. The effect of DDT on nitric oxide synthase activity in the liver, lungs and brain. Modern Problems Toxicology. 2000;3:3–7.
11.
Stefanov OV. Preclinical studies of drugs: guidelines. 2001.
12.
Stepanov YM. Breslavets YS The content of nitric oxide synthase in the mucous membrane of the stomach and duodenum in patients with NSAID gastropathy. Modern Gastroenterol. 2010;6(56):11–5.
The statements, opinions and data contained in the journal are solely those of the individual authors and contributors and not of the publisher and the editor(s). We stay neutral with regard to jurisdictional claims in published maps and institutional affiliations.
