ACTION OF HYDROGEN SULFIDE DONORS ON NITROSO-OXIDATIVE PROCESSES IN SMALL INTESTINE OF RATS WITH METHOTREXATE-INDUCED ENTEROPATHY

Abstract

Introduction. Medication-induced enteropathy plays an important part among factors leading to the development of small intestinal injury. There are some evidences indicating a potential preventive action of hydrogen sulfide (H₂S) donors against drug-induced enteropathies based on that fact that the use of the most of enterotoxic medications including anti-tumor drugs leads to the suppression of this gaseous mediator production.

The aim of the study – to compare the action of H₂S donors in small intestine of rats on parameters of NO-synthase system and oxidative stress under condition of methotrexate-induced enteropathy.

Research Methods. The experimental procedures were carried out on rats which on the background of methotrexate-induced enteropathy received H₂S donors NaHS (1 and 10 mg/kg) and L-cysteine. Following biochemical parameters were measured in small intestinal mucosa: activity of NO-synthases, myeloperoxidase, superoxide dismutase and catalase; concentrations of NO_x (nitrite/nitrate) and malonic dialdehyde. H₂S concentration was determined in blood serum.

Results and Discussion. Administration of methotrexate didn’t cause any visible changes of small intestine surface, however led to serious biochemical changes. NO concentration increased as a result of iNOS activation (more than fivefold (p≤0.01). Simultaneously concentration of H₂S decreased in blood serum. Administration of H_2.S donors practically returned these parameters to their normal value. Methotrexate-induced enteropathy caused the increase of myeloperoxidase activity by 66 %, p≤0.01, indicating of inflammatory process formation and activation of lipid peroxidation. Administration of NaHS didn’t cause any serious changes in myeloperoxidase activity, however increased SOD activity and practically retuned it to its norm.

Conclusions. Nirtoso-oxidative stress plays the key role in enteropathy formation resulted in methotrexate administration. H₂S donors modulate parameters of NO-synthase system and activity of SOD.