A standardized extract of Ginkgo biloba suppresses doxorubicin-induced oxidative stress and p53-mediated mitochondrial apoptosis in rat testes.
Br J Pharmacol
; 156(1): 48-61, 2009 Jan.
Article
in En
| MEDLINE
| ID: mdl-19133991
ABSTRACT
BACKGROUND AND PURPOSE:
Doxorubicin evokes oxidative stress and precipitates cell apoptosis in testicular tissues. The aim of this study was to investigate whether the Ginkgo biloba extract 761 (EGb), a widely used herbal medicine with potent anti-oxidant and anti-apoptotic properties, could protect testes from such doxorubicin injury. EXPERIMENTALAPPROACH:
Sprague-Dawley male rats (8 weeks old) were given vehicle, doxorubicin alone (3 mg kg(-1) every 2 days for three doses), EGb alone (5 mg kg(-1) every 2 days for three doses), or EGb followed by doxorubicin (each dose administered 1 day after EGb). At 7 days after the first drug treatment oxidative and apoptotic testicular toxicity was evaluated by biochemical, histological and flow cytometric analyses. KEYRESULTS:
Compared with controls, testes from doxorubicin-treated rats displayed impaired spermatogenesis, depleted haploid germ cell subpopulations, increased lipid peroxidation products (malondialdehyde), depressed antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase and glutathione), reduced antioxidant enzyme expression (superoxide dismutase) and elevated apoptotic indexes (pro-apoptotic modulation of Bcl-2 family proteins, intensification of p53 and Apaf-1, release of mitochondrial cytochrome c, activation of caspase-3 and increase of terminal deoxynucleotidyl transferase nick-end labelling/sub-haploid cells), while EGb pretreatment effectively alleviated all of these doxorubicin-induced abnormalities in testes. CONCLUSIONS AND IMPLICATIONS These results demonstrate that EGb protected against the oxidative and apoptotic actions of doxorubicin on testes. EGb may be a promising adjuvant therapy medicine, potentially ameliorating testicular toxicity of this anti-neoplastic agent in clinical practice.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Testis
/
Plant Extracts
/
Doxorubicin
/
Tumor Suppressor Protein p53
/
Apoptosis
/
Oxidative Stress
/
Antibiotics, Antineoplastic
/
Antioxidants
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Br J Pharmacol
Year:
2009
Document type:
Article
Affiliation country:
Taiwán