期刊
LIFE SCIENCES
卷 293, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2022.120354
关键词
Cyclophosphamide; Sildenafil; Placental injury; JNK; ERK; p38 MAPK
This study aimed to evaluate the effect of the phosphodiesterase 5 inhibitor, sildenafil (Sild), on cyclophosphamide (CYC)-induced placental injury in rats. The results showed that Sild significantly improved the oxidative stress, inflammation, and apoptosis caused by CYC.
Aims: Chemotherapeutic agents; cyclophosphamide (CYC) is used for treatment of cancer and autoimmune diseases. Grievously, CYC is non-selective as it affects both tumor and healthy cells resulting in systemic toxicity including placenta. The present study aimed to evaluate the effect of phosphodiesterase 5 inhibitor, sildenafil (Sild) on CYC-induced placental injury in rats.Materials and methods: Thirty-two female Wister rats were randomly divided into 4 experimental groups. Group 1: control pregnant group; Group 2: Sild-treated pregnant rats; Group 3: pregnant rats received CYC; Group 4: pregnant rats received Sild and CYC. Placental malondialdehyde (MDA), total nitrite/nitrate (NOx), reduced glutathione (GSH), tumor necrosis factor-alpha (TNF-alpha), platelet growth factor (PlGF), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38MAPK), extracellular signal-regulated kinase (ERK) and cleaved caspase-3 were measured. Histological changes, Nuclear Factor kappa-light-chain-enhancer of activated B (NF-Kappa B), Connexin 43 (GJA1) and proliferating cell nuclear antigen (PCNA) immuno-expressions were also evaluated.Key findings: CYC showed significant decrease in placental GSH, NOx, PlGF, GJA1 and PCNA immuno-expressions but significant increase in placental MDA, TNF-alpha, JNK, P38MAPK, ERK, caspase-3 and NF-kB immuno-expression. Sild showed significant improvement in all oxidative, inflammatory and apoptotic parameters.Significance: Sild is a promising protective drug against placental injury induced by CYC through antagonizing MAPK (JNK, ERK, and p38) signaling pathway with anti-oxidant, anti-inflammatory and anti-apoptotic effects.
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