Mansourpour Hamid, Ziari Katayoun, Motamedi Sahar Kalantar, Poor Amin Hassan
Shahid Beheshti University of Medical Science, Tehran, Iran and AJA University of Medical Science, Tehran, Iran.
Department of Pathology, AJA University of Medical Science, Tehran, Iran.
Eur J Transl Myol. 2019 Aug 6;29(3):8383. doi: 10.4081/ejtm.2019.8383. eCollection 2019 Aug 2.
Nitric oxide (NO) is involved in several biological processes, but its role in human melanogenesis and vitiligo need further studies. Previous studies revealed that exposure to UVA and UVB were capable of the inducing nitric oxide production in keratinocytes and melanocytes through the activation of constitutive nitric oxide synthase, whereas inducible nitric oxide synthase overexpression has been reported to play an important role in hyperpigmentary disorders. The aim of this study was to evaluate iNOS inhibitor aminoguanidine (AG) as a therapeutic agent in our mouse model of vitiligo. In this study, male C57BL/6J Ler-vit/vit mice were purchased to evaluate the effect of iNOS inhibitor (aminoguanidine) (50 and 100 mg/kg) and L-arginine (100 mg/kg) in a mouse model of vitiligo induced by monobenzone 40%. Moreover, we used phototherapy device to treat the mice with NBUVB as a gold standard.The findings revealed that monobenzone was capable of inducing depigmentation after 6 weeks. However, aminoguanidine in combination with monobenzone was decrease the effect of monobenzone, while L-arginine play a key role in promoting the effect of monobenzone (P<0.001). Based on the phototherapy, the efficacy of phototherapy significantly increased by adding L-arginine (P<0.05). Taken together, we suggest that iNOS inhibitor can be a novel treatment for the prevention and treatment of vitiligo by combination of NBUVB therapy, furthermore; NO agents like L-arginine could also increase the effectiveness of phototherapy. Taken together, this pilot study showed significant repigmentation of vitiligous lesions treated with iNOS inhibitor plus NBUVB therapy, where other aspect including expression of an inducible iNOS, NO and TNF levels remained to be evaluated in mice model.
一氧化氮(NO)参与多种生物学过程,但其在人类黑素生成和白癜风中的作用仍需进一步研究。先前的研究表明,暴露于UVA和UVB能够通过激活组成型一氧化氮合酶诱导角质形成细胞和黑素细胞产生一氧化氮,而诱导型一氧化氮合酶的过表达据报道在色素沉着过度性疾病中起重要作用。本研究的目的是评估诱导型一氧化氮合酶抑制剂氨基胍(AG)在我们的白癜风小鼠模型中作为治疗药物的效果。在本研究中,购买雄性C57BL/6J Ler-vit/vit小鼠以评估诱导型一氧化氮合酶抑制剂(氨基胍)(50和100mg/kg)和L-精氨酸(100mg/kg)在40%单苯甲醚诱导的白癜风小鼠模型中的作用。此外,我们使用光疗设备以窄谱中波紫外线(NBUVB)作为金标准治疗小鼠。研究结果显示,6周后单苯甲醚能够诱导色素脱失。然而,氨基胍与单苯甲醚联合使用可降低单苯甲醚的作用,而L-精氨酸在促进单苯甲醚的作用中起关键作用(P<0.001)。基于光疗,添加L-精氨酸可显著提高光疗效果(P<0.05)。综上所述,我们认为诱导型一氧化氮合酶抑制剂可通过与NBUVB疗法联合成为预防和治疗白癜风的一种新疗法,此外,像L-精氨酸这样的NO制剂也可提高光疗效果。综上所述,这项初步研究表明,诱导型一氧化氮合酶抑制剂加NBUVB疗法治疗的白癜风皮损有显著的色素再生,而在小鼠模型中,包括诱导型一氧化氮合酶的表达、NO和肿瘤坏死因子水平等其他方面仍有待评估。