Ornidazole On Mechanism Of Action Of Rats' Genetic Function

Ornidazole (Ornidazole, 1 - (3 - chlorine -2 - hydroxypropyl) -2 - methyl -5 - nitroimidazoles) is the third generation of nitroimidazoles derivatives after the metronidazole, tinidazole. It is a good anti-anaerobic bacteria and anti-protoplasts (such as trichomonas, etc.) infect drug. As a conventional drug, it is widely used in clinical treatment of male and female urogenital trichomonas and giardia infection, the role of the male reproductive has been of concern for people, too. In 1988, McClain RM has confirmed: given ornidazole (400 mg·kg-1) for 30 consecutive days to rats, the tail of the epididymis sperm activity compared with the control group is obviously lower. Two weeks after the withdrawal, sperm activity could resume. According to the role of the anti-microbial mechanism, the molecular structure of nitro was reducted by the nitro-reductase and produces short-lived free highly cytotoxicity radicals, they can damage sperm structural and trigger the reduction of animal reproductive function. This topic used to be the PK - PD experimental methods, to understand the reasons of Ornidazole anti-fertility of male rats, and to explore a new way on anti-fertility drugs. Seek to establish the indicators to evaluate the weak sperm animal model of pathological, male anti-fertility drugs to explore the role of new channels.The subject is divided into two parts; the first part is about the effect of Ornidazole on the environment of sperm mature male rats. This part of the experiment to be adopted PK-PD experiment, using HPLC to determinate ornidazole on rats'blood, testes and epididymis after given ornidazole (200mg·kg - 1) for 20 consecutive days; Parallel observed dynamic effect of ornedazole on carnitine concentration of epididymis and integrity of rats'sperm cell membrane, research to understand the epididymis Ornidazole impact of mature sperm in a sign of material - the content of carnitine; to understand the reasons of Ornidazole triggered animal sperm vitality of the possible reasons for declining. The second part though the angle of morphological and histological chemistry to investigate the effect on sperm formation and maturity of the places. Investigate the testis and epididymis and morphological changes in cells in the reproductive system of indicators of the characteristics of dynamic change, to got a better understanding of Ornidazole'role on the reproductive system of rats and its mechanism. The main results are as follow:①Results of ornidazole on rats'blood, testes and epididymis after oral gave male rats ornidazole (200mg·kg-1) for 20 consecutive days show that ratio of testes-blood and epididymis-blood zoomed, and reached highest in the last administration. Ratio of epididymis-testes maintained 1.12-1.16. Dynamic monitoring of drug show that ornidazole can through blood-pancreatic barrier and accumulated in epididymis and testes. This accumulation and administration was positive correlation. Cumulant in epididymis was higher than testes.②Parallel observed dynamic changes of carnitine show that it decreased quickly by given ornidazole, and retain the level of 26 mmol·L-1.③Test results of rats'sperm hypotension tumescence show that decreasing of carnitine in rats'epididymis could affect the quality of sperm. Ratio of rats'epididymis sperm hypotension tumescence on 10th day decreased 50% compared to control group.④IL-6 and IL-10 protein expression: compare 1-day drug treatment group and the 5-day group to the control group the changes do not express obvious differences; compare the medication for 10 days group to the control group the expressions are increased, but have no statistics significance; 15-days medication group and 20-days group compared with the normal group the expressions are increased more obvious, especially in epididymis.⑤Sex hormone-binding protein (SHBG) expression: in rats'epididymis organizations, the SHBG of 1-day group and the 5-day treatment group compare with the control group do not express obvious differences, the one of 10-day treatment group is less than the control group, 15-day drug treatment group and the group 20 days compared with the normal expression reduce more obvious. But the SHBG of drug-treated rats'testicular tissues expression showed no significant difference.Based on the above findings, Ornidazole effect the sperm quality first by interfering carnitine of initiative uptake in epididymis, then changing the environment of mature sperm, at last resulting in the decline of sperm quality.