Mechanism of antifertility effect of sulasalazine for male rats

Our purpose of this ecperiment was to study the antifertility effect of both metabolited of Sulfasalazine [Sulfaphridine(SP) and 5-Aminosalicylic acid(5-ASA)] in males and to detect the main target organ of Sulfasalazine. Nine-week-old mele Spraque Dawly rats, assigned at random to twelve groups, were treated with SP and 250, 125, 62.5, 31.3mg/kg/day, and 5-ASA at 153, 76.5, 38,3, 19.0mg/kg/day and distilled water, for a period of five weeks in addition to a normal diet. At the end od week-5, the fertility of each male rat was assessed by natural mating with virgin females. After mating male rats were sacrificed, the testes and the epididymides were removed and weighed. A part of the testicular tissu was submitted for flow cytometric DNA, analysis and a part for histological examination. Finally the concentration of N^4-Acetylsulfpyridine(AcSP), the main merabolite of Sulfapyridine, in the tested and the epididymides of the rats treated with SP(250mg/kg/day, for 5 weeks), was investigated by high pressure liquid shromatography. There was adramatical suppression in the fertility rate(number of fetuses/number of corpora lutea) in the groups with 250mg/kg/day and 125mg/kg/day. On the other hand, no suppression was observed in the other groups. In the mean testicular weight, the mean diameter of the seminiferous tuvules and the mean haploid cell ratio, all data were pairs of each group. The concentration of AcSP was confirmed to be significantly higher in the epididymis than in the testis. These finding strongly support the hypothesis that SP is the merabolite of Sufasalazaine, suppressing male fertility and that the main target portion of SP is epididymis.