METHODS: Group one constituted the control; group two was infected with T.b.r; group three was infected with T.b.r and treated with 2.2 mg/kg melarsoprol for 10 days; group four was infected with T.b.r and administered with GB 80 mg/kg for 30 days; group five was given GB 80mg/kg for two weeks before infection with T.b.r, and continued thereafter and group six was infected with T.b.r, administered with GB and treated with MelB.
RESULTS: Co-administration of MelB and GB improved the survival rate of infected mice. When administered separately, MelB and GB protected the integrity of the blood brain barrier and improved neurological function in infected mice. Furthermore, the administration of MelB and GB prevented T.b.r-induced microcytic hypochromic anaemia and thrombocytopenia, as well as T.b.r-driven downregulation of total WBCs. Glutathione analysis showed that co-administration of MelB and GB prevented T.b.r-induced oxidative stress in the brain, spleen, heart and lungs. Notably, GB averted peroxidation and oxidant damage by ameliorating T.b.r and MelB-driven elevation of malondialdehyde (MDA) in the brain, kidney and liver. In fact, the co-administered group for the liver, registered the lowest MDA levels for infected mice. T.b.r-driven elevation of serum TNF-α, IFN-γ, uric acid and urea was abrogated by MelB and GB. Co-administration of MelB and GB was most effective in stabilizing TNFα levels. GB attenuated T.b.r and MelB-driven up-regulation of nitrite.
CONCLUSIONS: Utilization of GB as an adjuvant therapy may ameliorate detrimental effects caused by T.b.r infection and MelB toxicity during late stage HAT.
方法:第一组为对照组;第二组感染T.b.r;第三组感染T.b.r,用2.2mg/kg美拉地普治疗10天;第四组感染T.b.r,用GB80mg/kg给药30天;第五组在感染T.b.r前两周给予GB80mg/kg,此后继续进行,第6组感染了T.b.r,用GB给药并用MelB治疗。
结果:MelB和GB的共同给药提高了感染小鼠的存活率。当单独施用时,MelB和GB保护了血脑屏障的完整性,并改善了感染小鼠的神经功能。此外,使用MelB和GB可以预防T.b.r诱导的小细胞性低色素性贫血和血小板减少症,以及T.B.R驱动的总WBC下调。谷胱甘肽分析表明,MelB和GB的共同给药可以防止T.b.r引起的大脑氧化应激,脾,脾心脏和肺。值得注意的是,GB通过改善T.b.r和MelB驱动的大脑中丙二醛(MDA)升高,避免了过氧化和氧化损伤,肾脏和肝脏。事实上,肝脏的共同给药组,记录了感染小鼠的最低MDA水平。T.b.r驱动的血清TNF-α升高,IFN-γ,尿酸和尿素被MelB和GB废除。MelB和GB的共同给药在稳定TNFα水平方面最有效。GB减弱了T.b.r和MelB驱动的亚硝酸盐上调。
结论:使用GB作为辅助治疗可以改善晚期HAT期间由T.b.r感染和MelB毒性引起的有害作用。