Hindawi Publishing Corporation
Journal of Biomedicine and Biotechnology
Volume 2012, Article ID 362049, 11 pages
doi:10.1155/2012/362049
Research Article
A Standardized Extract of Ginkgo biloba Neutralizes
Cisplatin-Mediated Reproductive Toxicity in Rats
Amr Amin,
1, 2
Christeena Abraham,
1
Alaaeldin A. Hamza,
1
Zeinab A. Abdalla,
1
Shaikha B. Al-Shamsi,
1
Saina S. Harethi,
1
and Sayel Daoud
3
1
Biology Department, United Arab Emirates University, Al Ain 17551, UAE
2
Zoology Department, Cairo University, Giza, Egypt
3
Histopathology Laboratory, Tawam Hospital in affiliation with Johns Hopkins Medicine, Al Ain, UAE
Correspondence should be addressed to Amr Amin, a.amin@uaeu.ac.ae
Received 26 January 2012; Revised 15 February 2012; Accepted 27 February 2012
Academic Editor: Metka Filipiˇ c
Copyright © 2012 Amr Amin et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
The aim of this study was to evaluate the protective effects of Ginkgo biloba (GB) against testicular damage and oxidative stress as
well as caudal sperm indices in a cisplatin- (CIS-) induced rodent model. Adult male Wistar rats were given vehicle, single i.p. dose
of CIS alone (10 mg/kg), GB alone (200 mg g/kg every day for five days), or single dose of CIS followed by GB (50, 100, or 200 mg/kg
every day for five days). On day 6, after the first drug treatment oxidative and apoptotic testicular toxicity was evaluated. CIS-treated
rats displayed decreased weights of testes and epididymis as well as caudal sperm count and motility. This reproductive toxicity was
accompanied with increased germ-cell degeneration in seminiferous tubules and increased germ-cell apoptosis, increased testicular
MDA levels and MPO activity, and decreased SOD and CAT activities in testes. Intensive expressions of COX-2, iNOS, and NF-κB
p65 in testicular tissues were detected in CIS-treated group. Oral GB administrations at all doses to CIS-treated rats effectively
alleviated all of the CIS-induced toxicity in reproductive system. The present results provide further insights into the mechanisms
of protection against CIS-induced reproductive toxicity and confirm the essential antioxidant potential of a GB extract.
1. Introduction
Chemotherapy has emerged as an efficient mode of treat-
ment for various carcinogenesis. Effective systemic drugs
are increasingly used to treat cancer patients. Cisplatin
(cis-diamminedichloroplatinum-II, CIS), one of the most
effective and widely prescribed anticancer drugs, is still used
in the treatment of many types of solid tumors including
testicular cancer [1, 2]. It has been proven highly effective
in curing testicular cancer in combination with other drugs
even at an advanced stage of the disease [3]. CIS kills cancer
cells by forming covalent adducts with the cellular DNA
molecules and thereby terminating the vital processes like
replication and transcription and inducing apoptosis [4].
In spite of its high efficiency in the treatment of testicular
cancer, CIS has severe adverse effects on spermatogenesis
and even leads to a condition of azoospermia [5, 6]. Sper-
matogenesis is a complex process which is highly influenced
by hormone molecules and temperature and involves an
array of testicular cells such as germ cells, Sertoli cells,
Leydig cells, and peritubular cells [7, 8]. Acute exposure
to antineoplastic agents like CIS has shown an increase in
the frequency of germ-cell apoptosis [9, 10] in experimental
animals. Moreover, it can also lead to decreased reproductive
organ weights, azoospermia, and degenerated spermatogenic
cells [11, 12]. The molecular mechanism by which CIS causes
reproductive toxicity and germ-cell apoptosis remains to
be elucidated. However, pathogenesis of testicular damage
followed by CIS exposure is generally ascribed to oxidative
stress mediated by increased free radical generation and
depletion of antioxidants. Free radicals have been reported
to mediate reactions responsible for a wide range of CIS-
induced side effects [9, 11]. Consequently, antioxidants have
been shown to protect nonmalignant cells and organs against
damage by CIS [9, 11, 13].
Ginkgo biloba (GB) has been used in traditional Chinese
medicine for about 5000 years, and it is one of the herbal
drugs that is used widely according to its antioxidant