Andrologia. 2020;00:e13855. wileyonlinelibrary.com/journal/and | 1 of 12
https://doi.org/10.1111/and.13855
© 2020 Wiley-VCH GmbH
1 | INTRODUCTION
Spermatogenesis is a multifaceted development in which highly spe-
cialised spermatozoa are produced by the male reproductive system
(O'Donnell et al., 2017). In this process, germinal epithelium consumes
a high amount of mitochondrial oxygen, which corresponds to high cell
division (Nishimura & L’Hernault, 2017). Hence, any interruption in this
process results in the reduction of sperm concentration and motility
and, finally, leads to infertility (Qu et al., 2019). Spermatogenesis is a
very delicate process that is profoundly affected by oxidative stress. In
testes, oxidative stress is known to disturb the Leydig cell function as
well as the capacity of germinal epithelium to transform into spermato-
zoa (Shadmehr et al., 2018). Several factors contributing to an increase
in oxidative stress are varicocele, infection, exposure to environmental
toxicants (Esteves, 2019) and many clinical medications. A broad class
of drugs used as painkillers, anti-infection medicines, contraceptives,
NSAIDs and, most importantly, cancer treatment drugs are known to
cause infertility. Drugs such as adriamycin and doxorubicin are known
to inhibit cancer growth. But despite the beneficial effects of these
drugs, there are many associated side effects such as cardiomyopathy,
liver infections, hair loss and infertility (Didwania, 2019).
Doxorubicin (Dox), a chemotherapeutic drug, is commonly used
in cancer treatment therapy. The administration of this anti-cancer
drug is known to induce oxidative stress (Caglayan et al., 2018).
Exposure to doxorubicin is associated with a variety of harmful
mechanisms, but the primary pathogenic mechanism appears to
Received: 4 May 2020
|
Revised: 25 August 2020
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Accepted: 31 August 2020
DOI: 10.1111/and.13855
ORIGINAL ARTICLE
Studies on the ameliorative potential of dietary supplemented
selenium on doxorubicin-induced testicular damage in mice
Sarvnarinder Kaur | Khushpreet Singh Maan | Shilpa Sadwal | Aniqa Aniqa
Department of Biophysics, Panjab
University, Chandigarh, India
Correspondence
Sarvnarinder Kaur, Department of
Biophysics, Panjab University, Chandigarh
160014, India.
Email: sarvnarinder@pu.ac.in
Funding information
University Grants Commission, Grant/Award
Number: SAP (F.4-12015/DSA-1 (SAP-4))
Abstract
Doxorubicin, a chemotherapeutic drug, is known to disrupt the normal spermatogen-
esis by excess oxidative stress. The present study describes the curative effects of
dietary supplemented selenium on doxorubicin-induced testicular damage in mice.
Four groups were included in the study: Group I(C), Group II (Se-0.5 ppm/kg diet),
Group III (Dox-3mg/kg body weight i.p.) and Group IV (Se + Dox). We analysed mi-
croscopic sperm parameters, histopathology, testicular germ cell kinetics, oxidative
stress levels, antioxidant levels and mRNA expression studies of apoptotic and stress
response markers. Sperm parameters were significantly reduced in doxorubicin-
treated group. Moreover, mice treated with doxorubicin showed an elevation in oxi-
dative stress markers as well as decreased redox ratio, and antioxidant levels were
observed in Group III (Dox). However, selenium supplementation ameliorated the
damage incurred by doxorubicin, by improving sperm parameters, antioxidant lev-
els and histoarchitecture of mice testes, and decreased the oxidative stress levels.
Selenium administration also reduced the levels of apoptotic caspases and stress-
activated kinases in Group IV (Se + Dox) when compared to Group III (Dox). In con-
clusion, selenium exhibits the curative effect against doxorubicin-induced testicular
damage in mice by attenuating stress conditions and associated apoptosis.
KEYWORDS
doxorubicin, oxidative stress, selenium, sperm parameters, testicular toxicity