Protective role of irbesartan against cyclophosphamide-induced testicular damage in rats via up-regulating PPAR-γ signaling and ameliorating NF-κB/NLRP3/IL-18 inflammatory axis.
Life Sci
; 289: 120218, 2022 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-34890588
ABSTRACT
BACKGROUND:
Cancer and its therapies can impact fertility in various ways, and therefore a growing number of cancer survivors face fertility as a significant concern. The cytotoxic alkylating agent cyclophosphamide (CP) is commonly used as an antineoplastic agent; unfortunately, its use is significantly associated with male infertility and damage to the reproductive system.AIM:
The present study aimed to assess the possible beneficial effects of Irbesartan (IRB) in a rat model of CP-induced testicular toxicity. MAINMETHODS:
The effects of treatment were assessed by measuring peroxisome proliferator-activated receptor gamma (PPAR-γ) expression via qRT-PCR, the immunohistochemical (IHC) assessment of apoptotic markers, NOD-like receptor protein 3 (NLRP3), and nuclear factor-κB (NF-κB), determination of the count and viability of epididymal sperm, oxidative stress markers via biochemical analysis, serum testosterone, caspase-1, and interleukin-18 (IL-18) levels via ELISA, histopathological assessment, and fibrosis by Masson's trichrome (MT) stain. KEYFINDINGS:
There was a significant increase in malondialdehyde (MDA), caspase-1, and IL-18 contents, NF-κB, NLRP3, Bcl-2-associated X protein (Bax), caspase-3, and MT staining in testicular tissue after CP administration compared to the normal control group. Whereas reduced glutathione (GSH), superoxide dismutase (SOD), PPAR-γ expression, B-cell lymphoma-2 (Bcl-2) staining, serum testosterone, and the count and viability of epididymal sperm were decreased compared to the normal control group. The IRB treatment has reversed CP-induced testicular toxicity.SIGNIFICANCE:
It is possible to conclude that IRB revealed a significant testicular protective effect against CP via antioxidant, anti-apoptotic, and anti-inflammatory effects.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doenças Testiculares
/
Transdução de Sinais
/
Regulação para Cima
/
NF-kappa B
/
Interleucina-18
/
Ciclofosfamida
/
PPAR gama
/
Proteína 3 que Contém Domínio de Pirina da Família NLR
/
Irbesartana
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article