Genistein reduces glycosaminoglycan levels in a mouse model of mucopolysaccharidosis type II.
OBJECTIVE
Mucopolysaccharidoses (MPS) are lysosomal storage disorders resulting from a deficit of specific lysosomal enzymes catalysing glycosaminoglycan (GAG) degradation. The typical pathology involves most of the organ systems, including the brain, in its severe forms. The soy isoflavone genistein has recently attracted considerable attention as it can reduce GAG synthesis in vitro. Furthermore, genistein is able to cross the blood-brain barrier in the rat. The present study was undertaken to assess the ability of genistein to reduce urinary and tissue GAG levels in vivo.


METHODS
We used mice with genetic deletion of iduronate-2-sulphatase (one of the GAG catabolizing enzymes) which provide a model of MPS type II. Two doses of genistein, 5 or 25 mg.kg(-1).day(-1), were given, in the diet for 10 or 20 weeks. Urinary and tissue GAG content was evaluated by biochemical and histochemical procedures.


RESULTS
Urinary GAG levels were reduced after 10 weeks' treatment with genistein at either 5 or 25 mg.kg(-1).day(-1). In tissue samples from liver, spleen, kidney and heart, a reduction in GAG content was observed with both dosages, after 10 weeks' treatment. Decreased GAG deposits in brain were observed after genistein treatment in some animals.


CONCLUSIONS
There was decreased GAG storage in the MPSII mouse model following genistein administration. Our results would support the use of this plant-derived isoflavone in a combined therapeutic protocol for treatment of MPS.
Friso
A
A
Department of Pediatrics, University of Padova, Italy.
Tomanin
R
R
Salvalaio
M
M
Scarpa
M
M
D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019833:Genistein / Q000008:administration & dosage / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000378:metabolism* / Q000652:urine; D007066:Iduronate Sulfatase / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016532:Mucopolysaccharidosis II / Q000188:drug therapy* / Q000235:genetics; D048789:Phytoestrogens / Q000008:administration & dosage / Q000494:pharmacology*
D006025:Glycosaminoglycans; D048789:Phytoestrogens; D019833:Genistein; D007066:Iduronate Sulfatase