UV-spectrophotometric screening of 5α-reductase inhibitors for benign prostatic hyperplasia treatment / 中国病理生理杂志
Chinese Journal of Pathophysiology
;
(12): 828-832, 2007.
Article
in Chinese
| WPRIM
| ID: wpr-408034
ABSTRACT
AIM:
Tranditional methods of screening drugs for benign prostatic hyperplasia(BPH)requires senile male animals such as dogs or rats.It consumes a long time to get the results. Over-expression of type Ⅱ5α-reductase in prastate induces BPH.A fast and efficient screening model of type Ⅱ5α-reductase inhibitors for BPH was set up in this paper.METHODS:
Microsomes were extracted from male Sprague-Dawley rat livers by gradient centrifugation.Type Ⅱ5α-reductase enzyme-catalyzed reaction was assayed by UV-spectrophotometry using testosterone as a substrate and NADPH as hydrogen donor.The change of enzymatic activity was recorded with a NADPH wavelength of 340 nm by subtracted descending velocity of the control(without 5α-reductase).Effects at different conditions(temperatures,pH,enzyme and testosterone concentrations)on 5α-reductase were assayed.RESULTS:
The suitable condition of type Ⅱ5α-reductase reaction Was defined as concentration of 109.05 mg protein/L enzyme(pH 6.00)with 2 μmol/L testosterone at 37℃.Michaelis'constant of type Ⅱ5α-reductase was 0.6μmol/L.Finasteride,a new drug for BPH,significantly inhibited activity of type Ⅱ 5α-reductase.IC50 of finasteride Was 64.1 nmol/L.As solvent of drugs,concentration of ethanol below 1.1% did not inhibite enzymatic activity(P>0.05).Concentration of ethanol above 1.6%could obviouslv suppress enzymatic activity(P<0.01).Daytime difference within five days had no significant difference(P>0.05).CONCLUSION:
A handy and fast screening method for type Ⅱ 5α-reductase inhibitors has been set up using UV-spectrophotometry.It may be used to screening drugs for BPH treatment.
Full text:
Available
Index:
WPRIM (Western Pacific)
Type of study:
Diagnostic study
/
Screening study
Language:
Chinese
Journal:
Chinese Journal of Pathophysiology
Year:
2007
Type:
Article
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