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

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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.

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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

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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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Authors and Affiliations

  1. Molecular Carcinogenesis and Chemoprevention Division, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi, 110 062, India

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

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  1. Abdul Lateef
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  2. Abdul Quaiyoom Khan
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Correspondence to Sarwat Sultana.

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Lateef, A., Khan, A.Q., Tahir, M. et al. Androgen deprivation by flutamide modulates uPAR, MMP-9 expressions, lipid profile, and oxidative stress: amelioration by daidzein. Mol Cell Biochem 374, 49–59 (2013). https://doi.org/10.1007/s11010-012-1504-7

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