World J Mens Health.  2015 Aug;33(2):73-80. 10.5534/wjmh.2015.33.2.73.

Protective Effects of KH-204 in the Bladder of Androgen-Deprived Rats

• Bae WJ
• Ha US
• Choi JB
• Kim KS
• Kim SJ
• Cho HJ
• Hong SH
• Lee JY
• Wang Z
• Hwang SY
• Kim SW

• KMID: 2032826
• DOI: http://doi.org/10.5534/wjmh.2015.33.2.73

Abstract

PURPOSE
We investigated the protective effects of the herbal formulation KH-204 in the bladder of androgen-deprived rats.
MATERIALS AND METHODS
Male rats aged eight weeks were randomly divided into four groups, containing eight rats each: sham operation only (normal control group), androgen-deprived only (androgen-deprived control group), and androgen-deprived followed by treatment with 200 mg/kg or 400 mg/kg of KH-204. After 0.5 mg/kg of leuprorelin was subcutaneously injected in the androgen-deprived groups, the oral administration of either distilled water in the two control groups or KH-204 in the treatment group was continued for four weeks. Serum testosterone levels, RhoGEF levels, nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-related parameters, oxidative stress, and histologic changes were evaluated after treatment.
RESULTS
Treatment with the herbal formulation KH-204 (1) increased serum testosterone levels; (2) restored the expression of RhoGEFs, endothelial NO synthase, and neuronal NO synthase; (3) increased the expression of superoxide dismutase; and (4) decreased bladder fibrosis.
CONCLUSIONS
Our results suggest that the positive effects of KH-204 on the urinary bladder may be attributed to its antioxidant effects or to an elevation in NO-cGMP activity.

Keyword

Antioxidants; Hypogonadism; Phytotherapy; Testosterone; Urinary bladder

MeSH Terms

Administration, Oral
Animals
Antioxidants
Fibrosis
Guanosine Monophosphate
Humans
Hypogonadism
Leuprolide
Male
Neurons
Nitric Oxide
Nitric Oxide Synthase
Oxidative Stress
Phytotherapy
Rats*
Rho Guanine Nucleotide Exchange Factors
Superoxide Dismutase
Testosterone
Urinary Bladder*
Water
Antioxidants
Guanosine Monophosphate
Leuprolide
Nitric Oxide
Nitric Oxide Synthase
Superoxide Dismutase
Testosterone
Water

Figure

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  Fig. 1 Serum testosterone levels increased by KH-204 treatment. Control: sham operation only, Androgen-dep.: androgen-deprived control group, 200 mg/kg: androgen deprivation followed by treatment with 200 mg/kg of KH-204, 400 mg/kg: androgen-deprivation followed by treatment with 400 mg/kg of KH-204. *p<0.05.

• 

  Fig. 2 Comparison of the mRNA expression of RhoGEFs in the bladder among the four groups. LARG: leukemia-associated RhoGEF, Control: sham operation only, Androgen dep.: androgen-deprived control group, 200 mg/kg: androgen deprivation followed by treatment with 200 mg/kg of KH-204, 400 mg/kg: androgen-deprivation followed by treatment with 400 mg/kg of KH-204. *p<0.05.

• 

  Fig. 3 Comparison of the expression levels of eNOS, nNOS and cyclic guanosine monophosphate (cGMP). (A, B) Densitometric analysis of eNOS and nNOS relative to beta-actin and (C) cGMP concentration in bladder tissue. Control: sham operation only, Androgen dep.: androgen-deprived control group, 200 mg/kg: androgen deprivation followed by treatment with 200 mg/kg of KH-204, 400 mg/kg: androgen-deprivation followed by treatment with 400 mg/kg of KH-204, eNOS: endothelial nitric oxide synthase, nNOS: neuronal nitric oxide synthase. *p<0.05.

• 

  Fig. 4 Comparison of the expression levels of oxdidative stress as reflected by total superoxide dismutase (SOD) expression in bladder tissue. Control: sham operation only, Androgen dep.: androgen-deprived control group, 200 mg/kg: androgen deprivation followed by treatment with 200 mg/kg of KH-204, 400 mg/kg: androgen-deprivation followed by treatment with 400 mg/kg of KH-204. *p<0.05.

• 

  Fig. 5 Comparison of histologic findings among the four groups. (A) Masson's trichrome staining. The scale bars shown in each figure represent 100 µm. (B) Bladder smooth muscle/collagen ratio. Control: sham operation only, Androgen dep.: androgen androgen-deprived control group, 200 mg/kg: androgen deprivation followed by treatment with 200 mg/kg of KH-204, 400 mg/kg: androgen-deprivation followed by treatment with 400 mg/kg of KH-204. *p<0.05.

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