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ชื่อบทความที่เผยแพร่ Tangeretin improves reproductive dysfunction in L-NAME-induced hypertensive male rats  
วัน/เดือน/ปี ที่เผยแพร่ 16 ธันวาคม 2562 
การประชุม
     ชื่อการประชุม Pharmacology 2019 
     หน่วยงาน/องค์กรที่จัดประชุม British Pharmacological Society (BPS) 
     สถานที่จัดประชุม Edinburgh International Conference Centre 
     จังหวัด/รัฐ Edinburgh, Scotland, United Kingdom 
     ช่วงวันที่จัดประชุม 15 ธันวาคม 2562 
     ถึง 17 ธันวาคม 2562 
Proceeding Paper
     Volume (ปีที่) 2019 
     Issue (เล่มที่)
     หน้าที่พิมพ์
     Editors/edition/publisher  
     บทคัดย่อ Introduction/Background & Aims Tangeretin, a flavonoid found in citrus fruit peels, has been reported to have antioxidantion and antiinflammatory effects [1]. This study investigated the effect of tangeretin on reproductive dysfunction in L-NAME-induced hypertensive male rats. Method/Summary of work Male SpragueDawley rats were induced hypertension using Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME 40 mg/kg) in drinking water for 5 weeks. The hypertensive rats were treated with tangeretin at dose 15 or 30 mg/kg or sildenafil (10 mg/kg) for the last two weeks. Mean arterial pressure (MAP), intracavernosal pressure (ICP) response to cavernous nerve stimulation (1-4 V, 15 Hz, for 1 min), tissue malondialdehyde (MDA) and plasma nitric oxide metabolites (NOx) were analyzed. Sperm concentration and motility were counted. Furthermore, endothelial nitric oxide synthase (eNOS) and steroidogenic acute regulatory protein (StAR) protein expression in penile and testicular tissues were evaluated. Serum testosterone and testicular morphology were evaluated. Statistical significance was determined using an ANOVA followed by a Fisher’s LSD post hoc test. Results/Discussion L-NAME hypertensive rats had high blood pressure, decreased ICP/MAP ratio, poor sperm quality and changes of seminiferous tubule morphology (p<0.05). eNOS and StAR expression in reproductive tissues were suppressed (p<0.05). An increase in tissue MDA, decrease in plasma NOx and serum testosterone were shown in hypertensive rats (p<0.05). Tangeretin significantly reduced MAP, improved male reproductive dysfunction (Table 1, 2), mitigated alterations of seminiferous tubule morphology and restored eNOS expression in penile and testicular tissues as well as StAR protein expression in testicular tissue in hypertensive rats(p<0.05). These were consistent with increases in plasma NOx and serum testosterone levels (Table 2) and decrease in tissue MDA in hypertensive rats treated with tangeretin (p<0.05). Sildenafil also had the beneficial effect on blood pressure and male reproductive dysfunction as tangeretin did but not for erectile responses in hypertensive rats.Table 1 Effect of tangeretin and sildenafil on erectile responses in hypertensive male ratsVoltagesMaximum ICP/MAP (%)Control+ VehicleL-NAME+ VehicleL-NAME+ tangeretin15 mg/kg/dayL-NAME+ tangeretin30 mg/kg/dayL-NAME+ sildenafil10 mg/kg/day1 V9.16 ± 2.293.51 ± 1.23a4.07 ± 1.03 a4.35 ± 0.98 a3.76 ± 1.05 a2 V18.44 ± 5.914.80 ± 1.28 a5.18 ± 1.73 a9.43 ± 1.50 4.40 ± 1.06 a3 V22.13 ± 5.344.97 ± 2.25 a3.69 ± 0.61 a13.36 ± 2.15 a, b4.27 ± 0.92 a4 V39.37 ± 4.406.02 ± 1.47 a8.04 ± 1.56 a17.46 ± 1.91 a, b6.73 ± 2.37 aData are expressed as mean ±SEM. (n= 6-8/group) a; P<0.05 vs control, b; P<0.05 vs L-NAMETable 2 Effect of tangeretin and sildenafil on sperm quality in hypertensive male ratsParametersControl+ VehicleL-NAME+ VehicleL-NAME+ tangeretin30 mg/kg/dayL-NAME+ sildenafil10 mg/kg/dayCaudal epididymal sperm concentration (x106/ mL)19.07 ± 1.0214.10 ± 0.65 a15.77 ± 0.96 b17.28 ± 0.59 bSperm motility (%)63.48 ± 2.0542.85 ± 1.96 a57.88 ± 2.57 b60.67 ± 0.66 bSerum testosterone levels (pg/mL)170.50± 20.5773.19± 26.27a164.21 ± 39.23 b150.35 ± 28.75 bData are expressed as mean ±SEM. (n= 6-8/group) a; P<0.05 vs control, b; P<0.05 vs L-NAME Conclusion(s) These findings cloud suggest that tangeretin reduces blood pressure, improves male reproductive dysfunction in nitric oxide (NO) deficient hypertension. The underlying mechanism might involve restoration of eNOS and StAR protein expression, along with increased NO bioavailability resulting from reducing oxidative stress. Reference(s) [1] Lee YY, Lee E-J, Park JS, Jang SE, Kim DH, Kim HS (2016) Anti-Inflammatory and Antioxidant Mechanism of Tangeretin in Activated Microglia. Journal of NeuroImmune Pharmacolog 2016; 11: 294-305.  
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