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Molecular and Cellular Biochemistry

, Volume 374, Issue 1–2, pp 49–59 | Cite as

Androgen deprivation by flutamide modulates uPAR, MMP-9 expressions, lipid profile, and oxidative stress: amelioration by daidzein

  • Abdul Lateef
  • Abdul Quaiyoom Khan
  • Mir Tahir
  • Rehan Khan
  • Muneeb U Rehman
  • Farrah Ali
  • Oday O. Hamiza
  • Sarwat Sultana
Article

Abstract

The growth and development of prostate gland is governed by testosterone. Testosterone helps in maintaining the adipose tissue stores of the body. It is well documented that with advancing age there has been a gradual decline in testosterone levels. Our aim was to study the protective role of daidzein on flutamide-induced androgen deprivation on matrix degrading genes, lipid profile and oxidative stress in Wistar rats. Sub-chronic (60 days) flutamide (30 mg/kg b.wt) administration resulted in marked increase in expressions of matrix degrading genes [matrix metalloproteases 9 and urokinase plasminogen activation receptor]. Additionally, it increased the levels of low density lipoproteins, total cholesterol, triglycerides, and lowered the levels of high density lipoproteins and endogenous antioxidant levels. Oral administration of daidzein (20 and 60 mg/kg b.wt) restituted the levels to normal. Daidzein administration resulted in amelioration of the prostate atrophy, degeneracy and invasiveness induced by flutamide. Our findings suggest that the daidzein may be given as dietary supplement to patients who are on androgen deprivation therapy, to minimize the adverse effects related to it and also retarding susceptibility of patients to cardiovascular diseases.

Keywords

Androgen receptor (AR) Flutamide Matrix metalloproteases 9 (MMP-9) Daidzein Urokinase plasminogen activation receptor (uPAR) Cholesterol 

Abbreviations

AR

Androgen receptor

BPH

Benign prostatic hyperplasia

CDNB

1-Chloro 2,4-dinitrobenzene

CaP

Cancer of prostate

CAT

Catalase

CVD’s

Cardiovascular diseases

DTNB

5,5′-Dithio-bis [2-nitrobenzoic acid]

EDTA

Ethylenediamine tetra acetic acid

GR

Glutathione reductase

GSH

Reduced glutathione

GSSG

Oxidized glutathione

HDL

High density lipoprotein

LDL

Low density lipoprotein

MMP-9

Matrix metalloproteases 9

PMS

Post-mitochondrial supernatant

NADPH

Reduced nicotinamide adenine dinucleotide phosphate

ROS

Reactive oxygen species

TG

Triglycerides

uPAR

Urokinase plasminogen activation receptor

VP

Ventral prostate

Notes

Acknowledgments

The author (SS) is thankful to the Department of Biotechnology (DBT), Govt. of India, New Delhi for providing funds and SRF to her student (AL) to carry out this work.

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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Abdul Lateef
    • 1
  • Abdul Quaiyoom Khan
    • 1
  • Mir Tahir
    • 1
  • Rehan Khan
    • 1
  • Muneeb U Rehman
    • 1
  • Farrah Ali
    • 1
  • Oday O. Hamiza
    • 1
  • Sarwat Sultana
    • 1
  1. 1.Molecular Carcinogenesis and Chemoprevention Division, Department of Medical Elementology and Toxicology, Faculty of ScienceJamia Hamdard (Hamdard University)New DelhiIndia

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