Title: The cytoprotective effect of the tripeptides h-glu-asp-gly-oh and h-lys-glu-asp-oh in indomethacin-induced enteropathy in rats

Biography:

Christina Nasadyuk is a physician, researcher and academic teacher with a PhD degree in Medical Biochemistry. Her current research is focused on the evaluation of the glycomic changes in gastrointestinal disorders as well as the role of cyclooxygenases, lipoxygenases, antioxidant and nitric oxide system in the processes of cytoprotection and ulceration of the stomach mucosa and the search for new gastroprotective peptides. The research is aimed at the reduction of NSAIDs gastrotoxicity. Has also scientific and management experience in cord blood banking industry, having contributed to its shaping and development in Ukraine. 

Abstract

Introduction. Nonsteroidal antiinflammatory drugs (NSAIDs) remain the most widely prescribed medications worldwide. Despite generally accepted strategies to reduce the side effects of these drugs towards stomach mucosa, there is increasing evidence that enteric mucosa is also susceptible to NSAIDs toxicity. However, uptodate medicine provides limited options for small intestine protection in chronic NSAIDs users. Short peptides were repeatedly reported to be promising agents for gastroprotective purposes [1,2].Aim of research was to assess the effect of H-Glu-Asp-Gly-OH and H-Lys-Glu-Asp-OH on NO-synthases (NOS) activity and lipid peroxidation processes in small intestinal mucosa (SIM).

 Material and methods. Studies were conducted on white male rats, devided into 4 groups (n=6 per group): 1) control; 2) intragastrically (ig) administered indomethacin (IND), 10 mg/kg; 3-4) ig pretreated with H-Glu-Asp-Gly-OH and H-Lys-Glu-Asp-OH (10µg) ig 30 min before IND introduction. 24h later rats were sacrificed, small intestine was isolated, washed with saline, exposed to gross inspection and in SIM homogenates NOS activity and MDA content were determined. In blood plasma L-arginine concentration was measured.

Results. Gross inspection of SIM did not reveal any visible lesions in experimental animals. However, biochemical investigations of SIM homogenates revealed that nonselective cyclooxygenase (COX)-1/COX-2 blockage with IND caused the development of nitrosooxidative stress. In SIM of IND-treated rats the increase of activities of NOS (28%, p<0.05) and iNOS (35%, p<0.05) was revealed, cNOS activity had tendency to decrease and L-arginine concentration in plasma decreased by 40% (p<0.05) compared to control group. MDA content increased by 35% (p<0.05) compared to control animals. In H-Lys-Glu-Asp-OH-pretreated rats iNOS activity decreased by 26% (p<0.05) in SIM and L-arginine concentartion in plasma increased by 27% (p<0.05) compared to the effect of IND. Pretreatment with H-Glu-Asp-Gly-OH did not cause any statistically significant difference in nitrosooxidative stress indices in SIM and blood plasma, however a tendency to decrease of iNOS activity in SIM, compared to isolated effect of IND, was noted.

Conclusions. Nonselectice COX-1/-2 blockage with IND causes nitrosooxidative stress in SIM. Tripeptide H-Lys-Glu-Asp-OH  reversed pathobiochemical changes in SIM, induced by COX-1/COX-2 blockage and its molecular mechanism of action needs further elucidation.