Toxicology and Immunotherapy Research Unit, Department of Biochemistry, Alex Ekwueme Federal University Ndufu Alike, Nigeria.
Toxicology and Immunotherapy Research Unit, Department of Biochemistry, Alex Ekwueme Federal University Ndufu Alike, Nigeria.
Immunobiology. 2022 May;227(3):152218. doi: 10.1016/j.imbio.2022.152218. Epub 2022 Apr 12.
The immunotoxicity mediated by cyclophosphamide (CYP) was earlier reported. Quercetin, due to its anti-oxidative/inflammatory properties elicits a plethora of health benefits. However, the influence of quercetin on the splenic/immunotoxicity linked with CYP-induced indoleamine 2,3-dioxygenase (IDO) is unavailable in the literature. We investigated the effects of quercetin on the splenic immunosuppressive IDO and hematological indices of immune response in rats. Animals were treated with CYP (100 mg/kg) alone or co-treated (CYP + quercetin [100 mg/kg + 50 mg/kg respectively]) at days 1, 3, 5, and 7. Results revealed that CYP treatment alone significantly provoked an oxidative-inflammatory response, increased serum kynurenine concentration, and concomitantly increased immunosuppressive IDO and tryptophan 2, 3-dioxygenase (TDO), in the spleen as well as altering hematological indices. Quercetin co-treatment enhanced activities of antioxidant enzymes, inhibited myeloperoxidase (MPO) activity, lowered levels of nitric oxide, interferon-Υ (IFN-Υ), and interleukin-6 (IL-6), and reduced kynurenine concentration as well as IDO/TDO activities. Quercetin co-treatment augmented white blood cell (WBC), CD4-T cells, and other hematological indices of the immune response. In conclusion, quercetin prevented CYP-induced alterations in immune response in rats by lowering the activities of immunosuppressive IDO and TDO, inhibiting oxidative-inflammatory stress, diminution of kynurenine concentrations, and augmenting hematological parameters.
环磷酰胺(CYP)介导的免疫毒性早先已有报道。槲皮素具有抗氧化/抗炎特性,可带来诸多健康益处。然而,关于槲皮素对 CYP 诱导的吲哚胺 2,3-双加氧酶(IDO)相关脾脏/免疫毒性的影响,文献中尚无记载。我们研究了槲皮素对大鼠脾脏免疫抑制 IDO 和免疫反应血液学指标的影响。动物在第 1、3、5 和 7 天分别接受 CYP(100mg/kg)单独或联合(CYP+槲皮素[分别为 100mg/kg+50mg/kg])治疗。结果表明,CYP 单独处理会显著引发氧化应激和炎症反应,增加血清犬尿氨酸浓度,并同时增加脾脏中免疫抑制 IDO 和色氨酸 2,3-双加氧酶(TDO)的活性,同时改变血液学指标。槲皮素联合治疗可增强抗氧化酶的活性,抑制髓过氧化物酶(MPO)的活性,降低一氧化氮、干扰素-γ(IFN-γ)和白细胞介素-6(IL-6)的水平,减少犬尿氨酸浓度以及 IDO/TDO 的活性。槲皮素联合治疗可增加白细胞(WBC)、CD4-T 细胞和免疫反应的其他血液学指标。总之,槲皮素通过降低免疫抑制 IDO 和 TDO 的活性、抑制氧化应激和炎症反应、降低犬尿氨酸浓度以及增加血液学参数,防止 CYP 诱导的大鼠免疫反应改变。