Molecular mechanism and health effects of 1,2-Naphtoquinone

Authors

  • Antonio Garcia Soares Department of Cellular and Integrative Physiology, University of Texas Health Science Center at San Antonio, USA. 7703 Floyd Curl Dr. San Antonio, TX, USA 78229, E-mail: soaresa@uthscsa.edu; Laboratory of Biochemical Pharmacology of Free Radicals, Inflammation and Pain, Departamento de Farmacologia, Instituto de Ciencias Biomedicas (ICB), University of Sao Paulo, Brazil. Av. Prof Lineu Prestes, 1524 Cidade Universitaria, Sao Paulo, SP CEP 05508-000, Brazil
  • Marcelo N. Muscara Laboratory of Biochemical Pharmacology of Free Radicals, Inflammation and Pain, Departamento de Farmacologia, Instituto de Ciencias Biomedicas (ICB), University of Sao Paulo, Brazil. Av. Prof Lineu Prestes, 1524 Cidade Universitaria, Sao Paulo, SP CEP 05508-000, Brazil
  • Soraia K. P. Costa Laboratory of Biochemical Pharmacology of Free Radicals, Inflammation and Pain, Departamento de Farmacologia, Instituto de Ciencias Biomedicas (ICB), University of Sao Paulo, Brazil. Av. Prof Lineu Prestes, 1524 Cidade Universitaria, Sao Paulo, SP CEP 05508-000, Brazil

DOI:

https://doi.org/10.17179/excli2020-2153

Keywords:

Naphthoquinone, free radicals, inflammation, cardiovascular system, review

Abstract

Extensive literature regarding the health side effects of ambient pollutants (AP) are available, such as diesel exhaust particles (DEPs), but limited studies are available on their electrophilic contaminant 1,2-Naphthoquinone (1,2-NQ), enzymatically derived from naphthalene. This review summarizes relevant toxicologic and biological properties of 1,2-NQ as an environmental pollutant or to a lesser degree as a backbone in drug development to treat infectious diseases. It presents evidence of 1,2-NQ-mediated genotoxicity, neurogenic inflammation, and cytotoxicity due to several mechanistic properties, including the production of reactive oxygen species (ROS), that promote cell damage, carcinogenesis, and cell death. Many signal transduction pathways act as a vulnerable target for 1,2-NQ, including kappaB kinase b (IKKbeta) and protein tyrosine phosphatase 1B (PTP1B). Antioxidant molecules act in defense against ROS/RNS-mediated 1,2-NQ responses to injury. Nonetheless, its inhibitory effects at PTP1B, altering the insulin signaling pathway, represents a new therapeutic target to treat diabetes type 2. Questions exist whether exposure to 1,2-NQ may promote arylation of the Keap1 factor, a negative regulator of Nrf2, as well as acting on the sepiapterin reductase activity, an NADPH-dependent enzyme which catalyzes the formation of critical cofactors in aromatic amino acid metabolism and nitric oxide biosynthesis. Exposure to 1,2-NQ is linked to neurologic, behavioral, and developmental disturbances as well as increased susceptibility to asthma. Limited new knowledge exists on molecular modeling of quinones molecules as antitumoral and anti-microorganism agents. Altogether, these studies suggest that 1,2-NQ and its intermediate compounds can initiate a number of pathological pathways as AP in living organisms but it can be used to better understand molecular pathways.

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Published

2020-06-03

How to Cite

Soares, A. G., Muscara, M. N., & Costa, S. K. P. (2020). Molecular mechanism and health effects of 1,2-Naphtoquinone. EXCLI Journal, 19, 707–717. https://doi.org/10.17179/excli2020-2153

Issue

Vol. 19 (2020)

Section

Original articles

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