ArticleActa pharmacologica Sinica2012
CPU86017-RS attenuate hypoxia-induced testicular dysfunction in mice by normalizing androgen biosynthesis genes and pro-inflammatory cytokines.
Article in Acta pharmacologica Sinica, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 13 citations in OpenAlex.
- Efficacy and mechanism of lipoic acid in the treatment of reproductive injury caused by perfluorooctanoic acid.Experimental and therapeutic medicine · 2023Article
- Alterations of estrous cycle, 3β hydroxysteroid dehydrogenase activity and progesterone synthesis in female rats after exposure to hypobaric hypoxia.Scientific reports · 2020Article
- Protective Effect of Apigenin on Acrylonitrile-Induced Inflammation and Apoptosis in Testicular Cells via the NF-κB Pathway in Rats.Inflammation · 2018Article
- Connexin 43 stabilizes astrocytes in a stroke-like milieu to facilitate neuronal recovery.Acta pharmacologica Sinica · 2015Article
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6 authors at 1 institution in 1 country.
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Abstract
aimDownregulation of androgen biosynthesis genes StAR (steroidogenic acute regulatory) and 3β-HSD (3β-hydroxysteroid dehydrogenase) contributes to low testosterone levels in hypoxic mice and is possibly related to increased expression of pro-inflammatory cytokines in the testis. The aim of this study is to investigate the effects of CPU86017-RS that block Ca(2+) influx on hypoxia-induced testis insult in mice.
methodsMale ICR mice were divided into 5 groups: control group, hypoxia group, hypoxia group treated with nifedipine (10 mg/kg), hypoxia groups treated with CPU86017-RS (60 or 80 mg/kg). Hypoxia was induced by placing the mice in a chamber under 10%±0.5% O2 for 28 d (8 h per day). The mice were orally administered with drug in the last 14 d. At the end of experiment the testes of the mice were harvested. The mRNA and protein levels of StAR, 3β-HSD, connexin 43 (Cx43), matrix metalloprotease 9 (MMP9), endothelin receptor A (ET(A)R) and leptin receptor (OBRb) were analyzed using RT-PCR and Western blotting, respectively. The malondialdehyde (MDA), lactate dehydrogenase (LDH), succinate dehydrogenase (SDH) and acid phosphatase (ACP) levels were measured using biochemical kits. Serum testosterone concentration was measured with radioimmunoassay.
resultsHypoxia significantly increased the MDA level, and decreased the LDH, ACP and SDH activities in testes. Meanwhile, hypoxia induced significant downregulation of StAR and 3β-HSD in testes responsible for reduced testosterone biosynthesis. It decreased the expression of Cx43, and increased the expression of MMP9, ETAR and OBRb, leading to abnormal testis function and structure. These changes were effectively diminished by CPU86017-RS (80 mg/kg) or nifedipine (10 mg/kg).
conclusionLow plasma testosterone level caused by hypoxia was due to downregulation of StAR and 3β-HSD genes, in association with an increased expression of pro-inflammatory cytokines. These changes can be alleviated by CPU86017-RS or nifedipine.
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