A standardized extract of Ginkgo biloba suppresses doxorubicin-induced oxidative stress and p53-mediated mitochondrial apoptosis in rat testes.
OBJECTIVE
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.


METHODS
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.


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
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.
Yeh
Y-C
YC
Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan.
Liu
T-J
TJ
Wang
L-C
LC
Lee
H-W
HW
Ting
C-T
CT
Lee
W-L
WL
Hung
C-J
CJ
Wang
K-Y
KY
Lai
H-C
HC
Lai
H-C
HC
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053477:Apoptotic Protease-Activating Factor 1 / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000009:adverse effects*; D020441:Ginkgo biloba; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008928:Mitochondria / Q000502:physiology; D018384:Oxidative Stress; D010936:Plant Extracts / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013091:Spermatogenesis / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D000096983:Ginkgo Extract
D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D053477:Apoptotic Protease-Activating Factor 1; D053148:Caspase 3; D045304:Cytochromes c; D004317:Doxorubicin; D005978:Glutathione; D005979:Glutathione Peroxidase; D008315:Malondialdehyde; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D013482:Superoxide Dismutase; D016159:Tumor Suppressor Protein p53; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract