TY - JOUR
T1 - Zinc protects cyclophosphamide-induced testicular damage in rat
T2 - Involvement of metallothionein, tesmin and Nrf2
AU - Maremanda, Krishna Prahlad
AU - Khan, Sabbir
AU - Jena, Gopabandhu
N1 - Funding Information:
We wish to acknowledge the financial assistance received from National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, India for carrying out the above experimentation. The authors would like to acknowledge Mr. B. Mallikarjun (Central instrumentation facility, NIPER) for his assistance in the Zn analysis.
PY - 2014/3/14
Y1 - 2014/3/14
N2 - The role of zinc (Zn) in the protection of germ cells against testicular toxicants has long been elucidated, but the exact molecular mechanisms have not yet been explored. Cyclophosphamide (CP), one of the most commonly used anticancer drugs survived ages of treatment, but the unwanted toxicity limits its clinical usage. The present investigation was aimed to explore the role of Zn and its associated pathways in CP-induced testicular toxicity in S.D. rat. CP was administered in saline 30. mg/kg 5× weekly for 3. weeks (total dose of 450. mg/kg) by i.p. route, while Zn was supplemented by oral route at the doses of 1, 3, 10. mg/kg/day for 3. weeks. CP significantly reduced Zn levels in serum and testes, body and testicular weight, sperm count and motility, spermiogenic cells, plasma testosterone and significantly increased the oxidative stress, sperm head abnormalities, sperm DNA damage with decreased chromatin and acrosome integrity; while Zn supplementation ameliorated the same. The present results demonstrated that Zn supplementation protected against CP-induced testicular damages by modulating metallothionein (MT), tesmin and Nrf2 associated pathways. Thus Zn supplementation during anticancer therapy might be potentially beneficial in reducing the off target effects associated with oxidative stress.
AB - The role of zinc (Zn) in the protection of germ cells against testicular toxicants has long been elucidated, but the exact molecular mechanisms have not yet been explored. Cyclophosphamide (CP), one of the most commonly used anticancer drugs survived ages of treatment, but the unwanted toxicity limits its clinical usage. The present investigation was aimed to explore the role of Zn and its associated pathways in CP-induced testicular toxicity in S.D. rat. CP was administered in saline 30. mg/kg 5× weekly for 3. weeks (total dose of 450. mg/kg) by i.p. route, while Zn was supplemented by oral route at the doses of 1, 3, 10. mg/kg/day for 3. weeks. CP significantly reduced Zn levels in serum and testes, body and testicular weight, sperm count and motility, spermiogenic cells, plasma testosterone and significantly increased the oxidative stress, sperm head abnormalities, sperm DNA damage with decreased chromatin and acrosome integrity; while Zn supplementation ameliorated the same. The present results demonstrated that Zn supplementation protected against CP-induced testicular damages by modulating metallothionein (MT), tesmin and Nrf2 associated pathways. Thus Zn supplementation during anticancer therapy might be potentially beneficial in reducing the off target effects associated with oxidative stress.
KW - Cyclophosphamide
KW - Metallothionein
KW - Nrf2
KW - Rat testes
KW - Tesmin
KW - Zinc
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U2 - 10.1016/j.bbrc.2014.02.055
DO - 10.1016/j.bbrc.2014.02.055
M3 - Article
C2 - 24565835
AN - SCOPUS:84896315184
SN - 0006-291X
VL - 445
SP - 591
EP - 596
JO - Biochemical and biophysical research communications
JF - Biochemical and biophysical research communications
IS - 3
ER -