Drug Designing: Open Access
Open Access
ISSN: 2169-0138
ISSN: 2169-0138
I.V. Tolstenok, O.A. Lebed ko, M.Yu. Fleishman
Central Research Laboratory of Federal State Budgetary Educational Institution of Higher Education �?«Far-East State Medical University�?» of the Ministry of
Healthcare of the Russian Federation
Khabarovsk Facility of Federal State Budgetary Scientific Institution �?«Far Scientific Centre of Physiology and Pathology of Respiration�?» - Scientific research
institute of Mother and Child Care, Russia
Posters & Accepted Abstracts: Drug Des
We studied the influence of small proline-rich peptides (SPRP), the family of glyprolines Pro-Gly-Pro (PGP) and Arg-Gly- Pro (RGP), on DNA synthesis and free radical oxidation in gastric mucosa (GM) of white mice in normal conditions and in the model of NSAID-associated gastropathy (indomethacin 250 mg/kg). Glyprolines were administered in dose 1 mg/ kg. Proliferative activity was evaluated with 3Ð-thymidine autoradiography (dosage 1 �?¼gKu/g). We counted labeling index (LI) in area of fundic glands. PGP showed higher activity than RGP. In physiological conditions peptides did not effect on LI. We observed that LI in â�?�?Indomethacine groupâ�? decreased by 67,7%, comparing to control group. In â�?�?PGP+Indomethacineâ�? group LI increased by 31% comparing to â�?�?Indomethacineâ�?. LI in â�?�?RGP+Indomethacineâ�? decreased by 5%. LI correlates with free radical oxidation. Administration of indomethacine caused oxidative stress. In â�?�?PGP+indomethacineâ�? group reduced manifestations of oxidative stress in GM, which was shown by lower chemiluminescence values in comparison with indomethacin group: activation of free radical oxidation (Ssp increased on 353%), increase of lipoperoxide concentrations (amplitude h on 475%), more rapid formation of peroxide radicals (Sind-1 increased on 475%), reduction of anti-oxidant antiradical defense (Sind-2 increased on 432%), and reduction of peroxide resistance (amplitude H increased on 586%). In â�?�?RGP+indomethacineâ�? group RGP peptide inhibited DNA synthesis and oxidative stress was more intensive in comparison with â�?�?PGP+indomethacineâ�? group: Ssp increased on 169%, amplitude h - on 190% , Sind-1 - on 208%, Sind-2 - on 159%, amplitude H - on 180%). We suppose that high dose of RGP peptide (1 mg/kg) provides high concentration of nitric oxide. The last activates the chain of biochemical reactions directed to apoptosis and reduces proliferation.
M.Yu. Fleishman is the director of Central Research Laboratory of Far-East State Medical University. In 2001 she had a research grant DAAD at the Essen Medical University under the leadership of prof Michel MC. She has published more than 58 papers (Fleishman M, Fleichman M).
Email: marfl@yandex.ru