Effects of 6-mercaptopurine (6-MP) on histomorphometric parameters of the rat bones.
6-Mercaptopurine (6-MP) is an antimetabolite. The drug inhibits DNA synthesis of cells by acting as a false analog of purines. 6-MP displays a cytostatic and immunosuppressive activity. The studies carried out so far focus mostly on recognizing the clinical effectiveness of 6-MP, particularly in treating autoimmune diseases, whereas its effect on the osseous tissue still remains unknown. We examined the effect of 6-MP on the osseous system in rats after a 4-week period of its administration by analyzing histomorphometric parameters and bone mass, mineral and calcium content. We also tested the reversal of the above changes after the lapse of 4 week-period during which 6-MP was not administered. Male Wistar rats were divided into 6 groups, each group was composed of 8 animals. Treatment of 6-MP started on day 2 of the experiment, and the drug was administered for 28 days, i.e. between day 2 and 29 in all groups examined. Changes in the histomorphometric parameters were examined in 3 groups 4 weeks after the first 6-MP or 0.9% NaCl administration: I - control group (0.9% NaCl solution), II - 6MP group (6-MP at the dose of 2.5 mg/kg po), III - 6-MP group (6-MP at the dose of 5 mg/kg po). Reversal of the changes was examined 8 weeks after the first 6-MP or 0.9% NaCl administration in 3 groups: IV - control group (0.9% NaCl solution), V - 6-MP group (6-MP at the dose of 2.5 mg/kg po), VI - 6-MP group (6MP at the dose of 5 mg/kg po). We demonstrated that 6-MP administered orally at a dose of 2.5 mg/kg po or at a dose of 5 mg/kg po for the period of 4 weeks inhibited the synthesis and mineralization of the osseous tissue by causing a disorder in histomorphometric parameters, which were not totally reversed after 4 weeks. 6-MP administered at a dose of 5 mg/kg also caused a reduction of mineral and calcium content, mostly in the cancellous bone, which returned to normal after 4 weeks.
Cegieła
Urszula
U
Department of Pharmacology, Silesian Medical University, Jagiellońska 4, PL 41-200 Sosnowiec, Poland.
Kaczmarczyk-Sedlak
Ilona
I
Sliwiński
Leszek
L
Nowińska
Barbara
B
D000284:Administration, Oral; D000818:Animals; D000963:Antimetabolites / Q000009:adverse effects*; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D015122:Mercaptopurine / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar
D000963:Antimetabolites; D015122:Mercaptopurine; D002118:Calcium