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NOVEL BIOPHARMACEUTICAL USE OF SILDENAFIL CITRATE IN TREATMENT OF UNEXPLAINED RECURRENT MISCARRIAGE: FIRST LONGITUDINAL CLINICAL STUDY OF 50 CASES FROM EGYPT
Mohamed El-Far*, Ikbal M. Abou Hashem, Abd El-Gawad E Abd El-Gawad, Nadia Bakry
ABSTRACT Present study was designed to fully investigate clinical as well as biopharmaceutical potential and mechanism of vaginally sildenafil citrate (SC) tablets on treatment of first trimester pregnant women with a history of unexplained recurrent spontaneous miscarriage (F-URSM), by altering blood antioxidants redox status as well as lipid peroxidation (MDA) and nitrosative stress (NO) biomarkers. Study was conducted on two groups of patients and a control group. The first patient group (F-URSM1) received SC (25 mg intravaginally, 4 times/day for 24 days, n= 20) and the second patient group (F-URSM2) received SC (25 mg intravaginally, 3 times/day for 13 days, n= 20). The control group comprised of 10 matched first trimester normal pregnant ladies (FTP). We evaluated effectiveness of this treatment on making changes on the balance between oxidant - antioxidant parameters as well as uterine indices to patient and control groups. SC treatment with different doses significantly increased antioxidants under investigation: [total antioxidant capacity (TAC), reduced glutathione (GSH), glutathione S- transferase (GST) , catalase (CAT), and superoxide dismutase (SOD)] than in untreated F-URSM patients (0 day), while MDA and NO also uterine indices (PI, RI, S/D ratio) were significantly decreased after treatment. In conclusion, we report novel evidence that intravaginal SC can correct and reverse the imbalance between ROS and antioxidant defense by restoring and augmenting the capacity of antioxidant as well as modulating lipid peroxidation and nitrosative stress. It may act by inhibiting myometrial contractions and improvement of vasoconstriction through increasing blood flow causing relaxation of uterine arteries. Keywords: Sildenafil citrate; Antioxidants; Unexplained recurrent spontaneous miscarriage (URSM); Oxidative stress; Abortion [Download Article] [Download Certifiate] |