Department of Toxicology, Faculty of Pharmacy, Gazi University, 06330 Hipodrom, Ankara, Turkey.
Parasitol Res. 2012 Oct;111(4):1725-30. doi: 10.1007/s00436-012-3015-6. Epub 2012 Jul 12.
Toxoplasma gondii is a very common obligate single-cell protozoan parasite which induces overproduction of interferon (IFN)-gamma and of other proinflammatory cytokines. Although immunomodulatory role of IFN-gamma favors tryptophan (Trp) degradation via indoleamine-2,3-dioxygenase (IDO) activity and is related with nitric oxide (NO) synthesis, the mechanism of antitoxoplasma activity is complex. In order to characterize the Trp degradation pattern during the acute T. gondii infection, serum Trp, kynurenine (Kyn), and urinary biopterin levels of mice were measured. The possible oxidative status was evaluated by the liver, spleen, brain, and serum malondialdehyde (MDA) and NO levels. Increased free radical toxicity may cause elevation in tissue MDA in T. gondii-infected mice, while unchanged serum MDA might indicate the increased oxidative stress due to T. gondii infection restricted to intracellular area. Elevated serum NO most probably might be due to the formation of reactive nitrogen radicals. The Kyn/Trp ratio was higher in T. gondii-infected mice compared to healthy animals (p < 0.05); however, it was not correlated with urinary biopterin. These results suggested that Trp degradation might be promoted by a pathway other than IDO during T. gondii infection and the reduction of Trp concentration favors the local immunosuppression and systemic tolerance.
刚地弓形虫是一种非常常见的专性单细胞原生动物寄生虫，它会引起干扰素 (IFN)-γ和其他促炎细胞因子的过度产生。虽然 IFN-γ的免疫调节作用通过吲哚胺 2,3-双加氧酶 (IDO) 活性有利于色氨酸 (Trp) 的降解，并与一氧化氮 (NO) 的合成有关，但抗弓形虫活性的机制很复杂。为了描述急性弓形虫感染期间 Trp 降解的模式，测量了感染小鼠的血清 Trp、犬尿氨酸 (Kyn) 和尿生物喋呤水平。通过肝脏、脾脏、大脑和血清丙二醛 (MDA) 和 NO 水平评估可能的氧化状态。感染弓形虫的小鼠组织中 MDA 升高可能是由于自由基毒性增加所致，而血清 MDA 不变可能表明由于感染弓形虫导致的氧化应激局限于细胞内区域而增加。血清 NO 升高很可能是由于活性氮自由基的形成。与健康动物相比，感染弓形虫的小鼠中的 Kyn/Trp 比值更高（p<0.05）；然而，它与尿生物喋呤无关。这些结果表明，在弓形虫感染期间，Trp 降解可能通过 IDO 以外的途径促进，Trp 浓度的降低有利于局部免疫抑制和全身耐受。
