Donida Bruna, Jacques Carlos Eduardo Diaz, Mescka Caroline Paula, Rodrigues Daiane Grigolo Bardemaker, Marchetti Desirèe Padilha, Ribas Graziela, Giugliani Roberto, Vargas Carmen Regla
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, UFRGS, Porto Alegre, RS, Brazil.
Programa de Pós-Graduação em Ciências Farmacêuticas, UFRGS, Porto Alegre, RS, Brazil; Serviço de Genética Médica, HCPA, Porto Alegre, RS, Brazil.
Clin Chim Acta. 2017 Mar;466:46-53. doi: 10.1016/j.cca.2017.01.007. Epub 2017 Jan 9.
Lysosomal Storage Disorders (LSD) comprise a heterogeneous group of >50 genetic disorders caused by mutations in genes that encode lysosomal enzymes, transport proteins or other gene products essential for a functional lysosomal system. As a result, abnormal accumulation of substrates within the lysosome leads to a progressive cellular impairment and dysfunction of numerous organs and systems. The exact mechanisms underlying the pathophysiology of LSD remain obscure. Previous studies proposed a relationship between oxidative stress and the pathogenesis of several inborn errors of metabolism, including LSD. Considering these points, in this paper it was reviewed oxidative stress and emerging antioxidant therapy in LSD, emphasizing studies with biological samples from patients affected by this group of conditions. These studies allow presuming that metabolites accumulated in LSD cause an increase of lysosomes' number and size, which may induce excessive production of reactive species and/or deplete the tissue antioxidant capacity, leading to damage in biomolecules. In vitro and in vivo evidence showed that cell oxidative process occurs in LSD and probably contributes to the pathophysiology of these disorders. In this context, it is possible to suggest that, in the future, antioxidants could come to be used as adjuvant therapy for LSD patients.
溶酶体贮积症（LSD）是由50多种基因紊乱组成的异质性疾病组，这些疾病是由编码溶酶体酶、转运蛋白或功能性溶酶体系统所必需的其他基因产物的基因突变引起的。因此，溶酶体内底物的异常积累会导致细胞渐进性损伤以及多个器官和系统的功能障碍。LSD病理生理学的确切机制仍不清楚。先前的研究提出氧化应激与包括LSD在内的几种先天性代谢缺陷的发病机制之间存在关联。考虑到这些因素，本文综述了LSD中的氧化应激和新兴的抗氧化治疗，重点介绍了对受这类疾病影响患者的生物样本进行的研究。这些研究推测，LSD中积累的代谢产物会导致溶酶体数量和大小增加，这可能会诱导活性物质的过度产生和/或耗尽组织抗氧化能力，从而导致生物分子受损。体外和体内证据表明，LSD中会发生细胞氧化过程，这可能对这些疾病的病理生理学有影响。在这种情况下，可以推测，未来抗氧化剂可能会用作LSD患者的辅助治疗。
