Effect of Propranolol Alone and in Combination with Pyrimethamine on Acute Murine Toxoplasmosis.
Effect of Propranolol Alone and in Combination with Pyrimethamine on Acute Murine Toxoplasmosis.
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DOI：
10.5812/jjm.22572
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发表时间：
2015-09
影响因子：
0.6
通讯作者：
Sarvi S
中科院分区：
文献类型：
--
作者：
Montazeri M;Daryani A;Ebrahimzadeh M;Ahmadpour E;Sharif M;Sarvi S
弓形虫病是一个世界性的公共卫生问题。这种并发症主要影响免疫缺陷患者和孕妇。弓形虫是一种机会性寄生虫，在高危人群中引起严重疾病和死亡，由于药物的副作用和低效，治疗变得越来越困难。在本研究中，我们观察了普萘洛尔的体内抗弓形虫效果。这项研究在两个单独的治疗前和治疗后组中进行。每组雌性Balb/c小鼠6个亚组18只(n=3)，观察心得安2和3 mg/kg/d、乙胺嘧啶50 mg/kg/d、心得安2和3 mg/kg/d+乙胺嘧啶和磷酸盐缓冲液(PBS；阴性对照)的抗弓形虫作用。在治疗前和治疗后组中，分别在1×103个弓形虫RH株速殖子腹腔攻击前、后4、24和48小时进行治疗。在攻击后第7天收集小鼠腹膜渗出物，记录寄生虫数，以生长抑制率和存活率为指标。预先给药组中，普萘洛尔2 mg/kg和3 mg/kg联合乙胺嘧啶对速殖子的抑制率分别为86%和98%，明显高于普萘洛尔2 mg/kg和3 mg/kg的抑制率(分别为37%和39%)和乙胺嘧啶(41%)。在后处理组中，所有联合治疗都显著降低了寄生虫负荷。普奈洛尔(2 mg/kg和3 mg/kg)对小鼠速殖子的生长抑制率分别为75%和51%，平均速殖子数分别为1 526±171.4和2 948±1452.8，而乙胺嘧啶的抑制率为99.9%。结果表明心得安对弓形虫感染有良好的预防和治疗作用。心得安还能增加乙胺嘧啶在联合治疗中的疗效。
Toxoplasmosis is a public health problem worldwide. This complication principally affects immunodeficient patients and pregnant women. Toxoplasma gondii is an opportunistic parasite, causing severe illness among and death of high-risk individuals and treatment is becoming increasingly difficult owing to side effects and low efficacies of drugs. In this study, we investigated the anti-Toxoplasma gondii efficacy of propranolol in vivo. This study was performed in two separate pre-treatment and post-treatment groups. In each group, 18 female Balb/c mice in six subgroups (n = 3) were used to assess the anti-Toxoplasma effect of propranolol at 2 and 3 mg/kg/day, pyrimethamine at 50 mg/kg/day, propranolol at 2 and 3 mg/kg/day plus pyrimethamine, and phosphate-buffered saline (PBS; as negative control). Treatment was performed 4, 24, and 48 hours before and after an intraperitoneal challenge of 1 × 103 tachyzoites of the virulent RH strain of T. gondii, in pre-treatment and post-treatment groups. Mice peritoneal exudates were collected on the seventh day after the challenge and parasite numbers were recorded as percent of growth inhibition and survival rate. In the pre-treatment group, results showed that propranolol at 2 and 3 mg/kg combined with pyrimethamine was more effective in inhibiting growth of tachyzoites (86% and 98%, respectively) when compared with propranolol at 2 and 3 mg/kg (37% and 39%, respectively) and pyrimethamine (41%) alone. In the post-treatment group, all combined treatments significantly reduced parasite load. The growth inhibition of tachyzoites in mice receiving propranolol (2 and 3 mg/kg) was 75% and 51%, with the mean tachyzoites count being 1526 ± 171.4 and 2948 ± 1452.8, respectively, compared with pyrimethamine treatment outcome, which represents 99.9% growth inhibition. Our results demonstrated the promising prophylactic and therapeutic effects of propranolol against T. gondii infection. Propranolol also increases the efficacy of pyrimethamine in combination therapies.