Genistein Reduces Glycosaminoglycan Levels in a Mouse Model of Mucopolysaccharidosis Type II

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 2010 Feb 9

PMID 20136838

Citations 40

Authors

A Friso

R Tomanin

M Salvalaio

M Scarpa

Affiliations

Soon will be listed here.

Abstract

Background And Purpose: 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.

Experimental Approach: 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.

Key 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 And Implications: 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.

Citing Articles

Efficacy of a Combination Therapy with Laronidase and Genistein in Treating Mucopolysaccharidosis Type I in a Mouse Model.

Malinowska M, Nowicka W, Kloska A, Wegrzyn G, Jakobkiewicz-Banecka J Int J Mol Sci. 2024; 25(4).

PMID: 38397051 PMC: 10889377. DOI: 10.3390/ijms25042371.

Actin Cytoskeleton Polymerization and Focal Adhesion as Important Factors in the Pathomechanism and Potential Targets of Mucopolysaccharidosis Treatment.

Gaffke L, Rintz E, Pierzynowska K, Wegrzyn G Cells. 2023; 12(13).

PMID: 37443816 PMC: 10341097. DOI: 10.3390/cells12131782.

A novel CRISPR/Cas9-based iduronate-2-sulfatase (IDS) knockout human neuronal cell line reveals earliest pathological changes.

Badenetti L, Manzoli R, Trevisan M, DAvanzo F, Tomanin R, Moro E Sci Rep. 2023; 13(1):10289.

PMID: 37357221 PMC: 10290981. DOI: 10.1038/s41598-023-37138-5.

Murine Fibroblasts and Primary Hepatocytes as Tools When Studying the Efficacy of Potential Therapies for Mucopolysaccharidosis Type I.

Wesierska M, Nowicka W, Kloska A, Jakobkiewicz-Banecka J, Malinowska M Int J Mol Sci. 2023; 24(1).

PMID: 36613977 PMC: 9820816. DOI: 10.3390/ijms24010534.

Mucopolysaccharidoses: Cellular Consequences of Glycosaminoglycans Accumulation and Potential Targets.

Leal A, Benincore-Florez E, Rintz E, Herreno-Pachon A, Celik B, Ago Y Int J Mol Sci. 2023; 24(1).

PMID: 36613919 PMC: 9820209. DOI: 10.3390/ijms24010477.

References

De Jong J, Wevers R . Measuring urinary glycosaminoglycans in the presence of protein: an improved screening procedure for mucopolysaccharidoses based on dimethylmethylene blue. Clin Chem. 1992; 38(6):803-7. View

Akiyama T, Ishida J, Nakagawa S, Ogawara H, Watanabe S, Itoh N . Genistein, a specific inhibitor of tyrosine-specific protein kinases. J Biol Chem. 1987; 262(12):5592-5. View

Miltyk W, Craciunescu C, Fischer L, Koch M, Lopaczynski W, Mahoney C . Lack of significant genotoxicity of purified soy isoflavones (genistein, daidzein, and glycitein) in 20 patients with prostate cancer. Am J Clin Nutr. 2003; 77(4):875-82. DOI: 10.1093/ajcn/77.4.875. View

Vera R, Sanchez M, Galisteo M, Villar I, Jimenez R, Zarzuelo A . Chronic administration of genistein improves endothelial dysfunction in spontaneously hypertensive rats: involvement of eNOS, caveolin and calmodulin expression and NADPH oxidase activity. Clin Sci (Lond). 2006; 112(3):183-91. DOI: 10.1042/CS20060185. View

Friso A, Tomanin R, Zanetti A, Mennuni C, Calvaruso F, La Monica N . Gene therapy of Hunter syndrome: evaluation of the efficiency of muscle electro gene transfer for the production and release of recombinant iduronate-2-sulfatase (IDS). Biochim Biophys Acta. 2008; 1782(10):574-80. DOI: 10.1016/j.bbadis.2008.07.001. View

Berasain C, Perugorria M, Latasa M, Castillo J, Goni S, Santamaria M . The epidermal growth factor receptor: a link between inflammation and liver cancer. Exp Biol Med (Maywood). 2009; 234(7):713-25. DOI: 10.3181/0901-MR-12. View

DAnna R, Cannata M, Marini H, Atteritano M, Cancellieri F, Corrado F . Effects of the phytoestrogen genistein on hot flushes, endometrium, and vaginal epithelium in postmenopausal women: a 2-year randomized, double-blind, placebo-controlled study. Menopause. 2008; 16(2):301-6. DOI: 10.1097/gme.0b013e318186d7e2. View

Tsai T . Concurrent measurement of unbound genistein in the blood, brain and bile of anesthetized rats using microdialysis and its pharmacokinetic application. J Chromatogr A. 2005; 1073(1-2):317-22. DOI: 10.1016/j.chroma.2004.10.048. View

Roberts A, Thomas B, Wilkinson A, Fletcher J, Byers S . Inhibition of glycosaminoglycan synthesis using rhodamine B in a mouse model of mucopolysaccharidosis type IIIA. Pediatr Res. 2006; 60(3):309-14. DOI: 10.1203/01.pdr.0000233037.00707.da. View

10.

Kim H, PETERSON T, Barnes S . Mechanisms of action of the soy isoflavone genistein: emerging role for its effects via transforming growth factor beta signaling pathways. Am J Clin Nutr. 1998; 68(6 Suppl):1418S-1425S. DOI: 10.1093/ajcn/68.6.1418S. View

11.

Bjornsson S . Simultaneous preparation and quantitation of proteoglycans by precipitation with alcian blue. Anal Biochem. 1993; 210(2):282-91. DOI: 10.1006/abio.1993.1197. View

12.

Urayama A, Grubb J, Banks W, Sly W . Epinephrine enhances lysosomal enzyme delivery across the blood brain barrier by up-regulation of the mannose 6-phosphate receptor. Proc Natl Acad Sci U S A. 2007; 104(31):12873-8. PMC: 1937559. DOI: 10.1073/pnas.0705611104. View

13.

McClain R, Wolz E, Davidovich A, Pfannkuch F, Edwards J, Bausch J . Acute, subchronic and chronic safety studies with genistein in rats. Food Chem Toxicol. 2005; 44(1):56-80. DOI: 10.1016/j.fct.2005.05.021. View

14.

Urayama A, Grubb J, Sly W, Banks W . Mannose 6-phosphate receptor-mediated transport of sulfamidase across the blood-brain barrier in the newborn mouse. Mol Ther. 2008; 16(7):1261-6. PMC: 2908959. DOI: 10.1038/mt.2008.84. View

15.

Boado R, Zhang Y, Zhang Y, Xia C, Wang Y, Pardridge W . Genetic engineering of a lysosomal enzyme fusion protein for targeted delivery across the human blood-brain barrier. Biotechnol Bioeng. 2007; 99(2):475-84. DOI: 10.1002/bit.21602. View

16.

Garcia A, Pan J, Lamsa J, Muenzer J . The characterization of a murine model of mucopolysaccharidosis II (Hunter syndrome). J Inherit Metab Dis. 2007; 30(6):924-34. DOI: 10.1007/s10545-007-0641-8. View

17.

Fanti P, Asmis R, Stephenson T, Sawaya B, Franke A . Positive effect of dietary soy in ESRD patients with systemic inflammation--correlation between blood levels of the soy isoflavones and the acute-phase reactants. Nephrol Dial Transplant. 2006; 21(8):2239-46. DOI: 10.1093/ndt/gfl169. View

18.

Liu L, Chen W, Xie J, Wong M . Neuroprotective effects of genistein on dopaminergic neurons in the mice model of Parkinson's disease. Neurosci Res. 2007; 60(2):156-61. DOI: 10.1016/j.neures.2007.10.005. View

19.

Friso A, Tomanin R, Alba S, Gasparotto N, Puicher E, Fusco M . Reduction of GAG storage in MPS II mouse model following implantation of encapsulated recombinant myoblasts. J Gene Med. 2005; 7(11):1482-91. DOI: 10.1002/jgm.790. View

20.

Jakobkiewicz-Banecka J, Piotrowska E, Narajczyk M, Baranska S, Wegrzyn G . Genistein-mediated inhibition of glycosaminoglycan synthesis, which corrects storage in cells of patients suffering from mucopolysaccharidoses, acts by influencing an epidermal growth factor-dependent pathway. J Biomed Sci. 2009; 16:26. PMC: 2653532. DOI: 10.1186/1423-0127-16-26. View