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NEW APPROACHES TO PREVENTION OF NSAID-GASTROPATHY

Introduction: At present, the issue of gastric mucosal damage, induced by the use of non-steroidal anti-inflammatory drugs, remains unresolved.

Objectives: The development of new methods of prevention of NSAID-gastropathies with oral coursework use of taurine and procaine, as well as the study of cellular mechanisms of the damaging effect of diclofenac sodium and Ketorolac tromethamine.

Methods: The methodological approach was based on a range of theoretical, pharmacological, histological, statistical, biophysical methods.

Results and discussion: Diclofenac sodium and ketorolac tromethamine, being in direct contact with cell membranes, cause a change in the structural and functional properties that present in the defect formation. This resulted in a decrease in the acid and hypo-osmotic resistance of model cells due to the broken or weakened bonds stabilizing the proteins molecules in membrane (which is associated with the dissociation of NH+-groups of the imidazole ring of histidine, the terminal α-amino groups (not less than 10.5% relative to the control), sulfhydryl groups of cysteine, phenolic groups of tyrosine, ε-amino groups of lysine (not less than 8.7%)). In experiments in vitro and in vivo procaine reduces the damaging effect of Ketorolac trometamina 28% and 19.7%, respectively, the formation of hidden defects reduced by 69% when taurine cellular damage was reduced by 54% and 19.7% of the latent defects is less than 74%.

Conclusion: Prophylactic intragastric administration of procaine or taurine for 7 days before ketorolac tromethamine administration significantly reduces the amount of erosive and ulcerative defects (87% and 90%, respectively).

Иллюстрации

Fig. 1. The study design

Table 1. Study of the efficiency of procaine and taurine for the prevention of ketorolac tromethamine ulcerogenic effects (M±m)

Note: * - the differences are statistically significant at р<0.05

Fig. 2. Histoarchitecture of the gastric mucosa in the prevention of ketorolac tromethamine-induced NSAID-gastropathy by taurine and procaine

Note: A) control; B) ketorolac tromethamine; С) ketorolac tromethamine + taurine; D) ketorolac tromethamine + procaine (Color. gem-eosin. Magnification, appr. 7, v. 40)

Table 2. Indices of acid and hypo-osmotic hemolysis of erythrocytes modified with sodium diclofenac depending on incubation time (M±m)

Note: ** - the differences are statistically significant at p <0.001, * - the differences are statistically significant at p <0.05 

 

Table 3. Indices of acid and hypo-osmotic hemolysis of erythrocytes modified with ketorolac tromethamine depending on incubation time (M±m)

Note: ** - the differences are statistically significant at p <0.001, * - the differences are statistically significant at p <0.05

Table 4. Indices of acid and hypo-osmotic hemolysis for erythrocytes modified by procaine depending on incubation time  (M±m)

Note: ** - the differences are statistically significant at p <0.001, * - the differences are statistically significant at p <0.05

 

Table 5. Indices of acid and hypo-osmotic hemolysis for erythrocytes modified with taurine depending on incubation time (M±m)

Note: ** - the differences are statistically significant at p <0.001, * - the differences are statistically significant at p <0.05

Table 6. Indices of acid and hypo-osmotic hemolysis of erythrocytes modified with ketorolac tromethamine in combination with procaine and taurine (M±m)

Note: ** - the differences are statistically significant at p <0.001, * - the differences are statistically significant at p <0.05   

Fig. 3. The values ​​of Kmax (relative units) of erythrocyte acid hemolysis against the background of the use of ketorolac tromethamine and its combination with taurine and procaine.

Table 7. Values ​​of Kmax, Gsph and G120 indices of acid and hypo-osmotic hemolysis against the combination of ketorolac with procaine and taurine in vivo (M±m)

Note: ** - the differences are statistically significant at p <0.001, * - the differences are statistically significant at p <0.05

Table 8. Oxyhemoglobin buffer properties under the action of ketorolac tromethamine in combination with procaine and taurine (M±m)

Note: * - the differences are statistically significant at p <0.05

DOI: 10.18413/2313-8971-2017-3-3-55-70
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