Doxorubicin-induced testicular damage is related to PARP-1 signaling molecules in mice.
Pharmacol Rep
; 71(4): 591-602, 2019 Aug.
Article
em En
| MEDLINE
| ID: mdl-31174020
ABSTRACT
BACKGROUND:
Doxorubicin (DOX), is a chemotherapeutic agent, which evokes oxidative stress and cell apoptosis in testicular tissue. It is known that the activation of the nuclear enzyme poly (ADP-ribose) polymerase (PARP), leading to apoptosis induced by DOX. The aim of the present study is to investigate whether PARP pathway has a role in DOX-induced testicular damage and infertility utilizing pharmacological PARP-1 inhibitor, PJ34, and PARP-1 knockout mice model.METHODS:
Firstly, we assessed the activation of PARP pathway after DOX-induction at various hours by immunohistochemistry and western blot analysis. Secondly, we evaluated the role of PARP pathway in DOX-induced testicular damage, sperm motility, and fertility with pharmacological inhibition of PARP by using PJ34. Finally, we aimed to correlate a functional relationship between PARP-1 and DOX using PARP-1 knockout mice in DOX-induced testicular damage. Doxorubicin levels in plasma and testis tissue were also assessed.RESULTS:
In DOX-induced group; PARP-1, PAR and apoptotic pathway protein expressions, increased significantly. In DOX + PJ34 group; PAR, cytochrome c, and AIF levels decreased significantly. Testicular weights, sperm motility, and mean the number of pups per litter decreased in DOX-induced group after 28 days, however they were similar to the control group in DOX-PJ34 group. In PARP-1 KO group, seminiferous tubule morphology was impaired significantly after 28 days of DOX-administration.CONCLUSIONS:
Our study indicates that DOX-induced testicular damage may be related to over-activation of PARP-1. PJ34 application was effective in preventing severe testicular damage caused by DOX-injection and may be considered for fertility protection against DOX-induced testicular damage.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Motilidade dos Espermatozoides
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Testículo
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Doxorrubicina
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Poli(ADP-Ribose) Polimerase-1
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Infertilidade Masculina
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Antibióticos Antineoplásicos
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article