Disease relevance of Nitrol

• The toxicity for the cytotoxicant 1-nitronaphthalene is highly localized in the airway epithelium [1].
• This study demonstrates a site-selective synergy between the copollutants ozone and 1-nitronaphthalene in the production of acute lung injury [2].
• Interstitial pneumonitis and edema were observed in all animals treated with 1-nitronaphthalene, and was usually associated with bronchioles containing necrotic epithelium [3].

High impact information on Nitrol

• This is the first in a series of articles employing this microarray for detecting gene expression changes during acute injury produced by 1-nitronaphthalene and subsequent repair [1].
• These results suggest the importance of other P450 enzymes in the epoxidation/bioactivation of 1-nitronaphthalene [4].
• CYP2F4 failed to display an enhanced ability to bioactivate 1-nitronaphthalene, an ability that could have potentially compensated for the lower CYP2F pulmonary expression levels in the rat, yet equal species susceptibilities [4].
• Accordingly, infant monkey airway subcompartments, including trachea, proximal, midlevel, distal airways, and parenchyma, were incubated with naphthalene or 1-nitronaphthalene to define metabolism at both high (500 microM) and low (50 microM) substrate concentrations [5].
• This is compared with denudation of 4% of the basement membrane of FA-exposed rats administered 100 mg/kg 1-nitronaphthalene; only 25% of the cells remaining on the epithelium were necrotic [2].

Chemical compound and disease context of Nitrol

• The results from this work suggest that CYP2F2 1) plays a key role in the species- and cell-selective toxicity of naphthalene and 2) efficiently metabolizes a number of other substrates, including the lung toxicant 1-nitronaphthalene [6].
• The objective of this study was to determine how retinol would affect the pulmonary and hepatic toxicity caused by 1-nitronaphthalene (1-NN) [7].
• Toxicity of 3-methylindole, 1-nitronaphthalene and paraquat in precision-cut rat lung slices [8].

Biological context of Nitrol

• 1-Nitronaphthalene is a pulmonary cytotoxicant requiring metabolic activation [2].
• 1-Nitronaphthalene (1-NN) has been identified in the U.S. National Toxicology Program as a non-carcinogen showing some evidence of in vitro genotoxicity [9].

Anatomical context of Nitrol

• No differences in the susceptibility of intrapulmonary airways or trachea to 1-nitronaphthalene were observed between filtered air- and ozone-exposed rats [2].
• To test whether exposure to ozone alters pulmonary cytochrome P450 monooxygenase-mediated metabolism of xenobiotics, rates of 1-nitronaphthalene (1-NN) metabolism were measured in microsomes prepared from trachea, intrapulmonary airways, and distal lung of rats exposed to filtered air (FA) or ozone (O(3)) (0.8 ppm 8 h/day for 90 days) [10].
• Metabolic fingerprints, in the form of patterns of high-concentration endogenous metabolites, of 1-nitronaphthalene (NN)-induced lung toxicity have been elucidated in bronchoalveolar lavage fluid (BALF), urine, blood plasma, and intact lung and liver tissue using NMR spectroscopy-based metabolic profiling [11].
• Reactive metabolites of naphthalene and 1-nitronaphthalene covalently bind to proteins, and the formation of covalent adducts correlates with airway epithelial cell injury in rodent models [12].

Associations of Nitrol with other chemical compounds

• Glutathione conjugation of electrophilic metabolites of 1-nitronaphthalene in rat tracheobronchial airways and liver: identification by mass spectrometry and proton nuclear magnetic resonance spectroscopy [13].
• all-trans-retinol modulation of nitronaphthalene-induced lung and liver injury in male Sprague-Dawley rats [14].

Analytical, diagnostic and therapeutic context of Nitrol

• High-resolution histopathology, transmission electron microscopy, and morphometry revealed significantly greater 1-nitronaphthalene toxicity in the central acinar region of O(3)- compared with FA-exposed rats [2].
• The studies presented here describe morphological changes in the lung and liver at several time intervals following a single injection of 1-nitronaphthalene (100 mg/kg, i.p.) in male Sprague-Dawley rats using transmission and scanning electron microscopy [3].
• 1-Nitronaphthalene (1-NN) produced respiratory distress and centrilobular liver necrosis in male Sprague-Dawley rats after a single intraperitoneal injection (100 mg kg-1) [15].

References