Pulmonary toxicity and fibrogenic response of carbon nanotubes

Abstract

Carbon nanotubes (CNTs) have been a subject of intensive research for a wide range of applications. However, because of their extremely small size and light weight, CNTs are readily inhaled into human lungs resulting in increased rates of pulmonary disorders, most notably fibrosis. Several studies have demonstrated the fibrogenic effects of CNTs given their ability to translocate into the surrounding areas in the lung causing granulomatous lesions and interstitial and sub-pleural fibrosis. However, the mechanisms underlying the disease process remain obscure due to the lack of understanding of the cellular interactions and molecular targets involved. Interestingly, certain physicochemical properties of CNTs have been shown to affect their respiratory toxicity, thereby becoming significant determinants of fibrogenesis. CNT-induced fibrosis involves a multitude of cell types and is characterized by the early onset of inflammation, oxidative stress and accumulation of extracellular matrix. Increased reactive oxygen species activate various cytokine/growth factor signaling cascades resulting in increased expression of inflammatory and fibrotic genes. Profibrotic growth factors and cytokines contribute directly to fibroblast proliferation and collagen production. Given the role of multiple players during the pathogenesis of CNT-induced fibrosis, the objective of this review is to summarize the key findings and discuss major cellular and molecular events governing pulmonary fibrosis. We also discuss the physicochemical properties of CNTs and their effects on pulmonary toxicities as well as various biological factors contributing to the development of fibrosis.

Oxidative stress pathways involved in cytotoxicity and genotoxicity of titanium dioxide (TiO2) nanoparticles on cells constitutive of alveolo-capillary barrier in vitro

“…Activation of these proteins in our experimental conditions was also concomitant with the persistence of DNA lesions detected by the activation of H2AX, and may correspond also to apoptotic DNA fragmentation for HPMEC-ST1.6R cells specifically (Sluss and Davis, 2006). The JNK group of protein kinases are generally activated in response to a number of cellular stresses, high osmolarity and oxidation (Ip and Davis, 1998), but may be a major concern in term of promotion of inflammatory response (Manke et al, 2013a(Manke et al, , 2013bShi et al, 2004). Here, SAPK/JNK activation seems appeared in cell lines sensitive to endogenous variation of redox status.…”

“…protein, associated to ROS overproduction were known to impact apoptosis induction or cell cycle regulation (Ono and Han, 2000;Taylor et al, 2013), and may also be considered as an important pathway in inflammation (Manke et al, 2013a(Manke et al, , 2013b and pathology of pulmonary hypertension and pulmonary vascular remodeling (Church et al, 2012;Han et al, 2013), as well as microvascular dysfunctions (Wang et al, 2010;Nurkiewicz et al, 2011).…”

Recent progress in synthesis, properties and potential applications of SiC nanomaterials

“…De hecho, la mayoría de las propiedades típicas que los caracteriza (pequeño tamaño en al menos una dimensión entre 1-100 nm, su gran área superficial por peso y su reactividad) son precisamente las propiedades que los hacen tecnológica-mente tan valiosos y estas son probablemente las razones para sus efectos dañinos potenciales [65,66,67].…”

Health concerns of various nanoparticles: A review of their in vitro and in vivo toxicity

“…The most important damages to the lung tissue by carbon NPs are oxidative stress, neutrophilic inflammation and genotoxicity inducing asbestosis, fibrosis, and lung tumor [203]. In rats, the toxicity of these NPs includes neutrophilic inflammation, granulomatous inflammation, cytokine production, thickening of the tissue, and fibrosis [204].…”