CBLB502, a Toll-like receptor 5 agonist, offers protection against radiation-induced male reproductive system damage in mice.
Biol Reprod
; 100(1): 281-291, 2019 01 01.
Article
em En
| MEDLINE
| ID: mdl-30084935
ABSTRACT
CBLB502, a Toll-like receptor (TLR)5 agonist derived from Salmonella flagellin, was shown to protect mammalian hematopoietic and gastrointestinal systems from acute irradiation syndrome and to stimulate regeneration. To explore whether CBLB502 can improve testicular injuries caused by irradiation, mice were intraperitoneally injected with 0.2 mg/kg CBLB502 or vehicle control 30 min prior to applying 5.0 Gy ionizing radiation (IR). We observed these mice for the following 120 days and determined that CBLB502 pretreatment alleviated IR-induced oxidative stress, alleviated the distorted architecture of seminiferous tubules, reversed the decline of sperm quantity and quality, and helped recover male mouse fertility. Additionally, CBLB502 efficiently reduced DNA damage and chromosomal aberrations in IR-treated mice and their offspring. Due to the suppression of p53-dependent apoptosis, in IR-treated mice, CBLB502 was shown to significantly activate the nuclear factor kappa B (NFκB) pathway and reduce the apoptotic rate in association with an increase in anti-apoptotic B-cell lymphoma 2 levels and a decrease in the levels of DNA repair protein and proliferating cell nuclear antigen. Moreover, an IR-induced reduction in serum testosterone and superoxide dismutase levels and an increase in malondialdehyde levels were considerably reversed in CBLB502-pretreated mice. No significant reverse effects were found in Tlr5 knockout mice, suggesting that protection of the testis against IR by CBLB502 is primarily dependent on the TLR5 signaling pathway. Our results may help further investigations into potential CBLB502 applications for the protection of the male reproductive system during radiotherapy.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Lesões por Radiação
/
Protetores contra Radiação
/
Radioterapia
/
Doenças dos Genitais Masculinos
/
Genitália Masculina
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Biol Reprod
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China