期刊
BRITISH JOURNAL OF PHARMACOLOGY
卷 156, 期 1, 页码 48-61出版社
WILEY
DOI: 10.1111/j.1476-5381.2008.00042.x
关键词
EGb; doxorubicin; testis; apoptosis; oxidative stress; cytochrome c; p53
资金
- Yen-Tjing-Ling Medical Foundation [CI-96]
- Taichung Veteran General Hospital Research [TCVGH-963108C, TCVGH-966303C]
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. Experimental approach: 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. Key results: 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.
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