Lung injury, inflammation and Akt signaling following inhalation of particulate hexavalent chromium

Abstract

Certain particulate hexavalent chromium [Cr(VI)] compounds are human respiratory carcinogens that release genotoxic soluble chromate, and are associated with fibrosis, fibrosarcomas, adenocarcinomas and squamous cell carcinomas of the lung. We postulate that inflammatory processes and mediators may contribute to the etiology of Cr(VI) carcinogenesis, however the immediate (0–24 hours) pathologic injury and immune responses after exposure to particulate chromates have not been adequately investigated. Our aim was to determine the nature of the lung injury, inflammatory response, and survival signaling responses following intranasal exposure of BALB/c mice to particulate basic zinc chromate. Factors associated with lung injury, inflammation and survival signaling were measured in airway lavage fluid and in lung tissue. A single chromate exposure induced an acute immune response in the lung, characterized by a rapid and significant increase in IL-6 and GRO-α levels, an influx of neutrophils, and a decline in macrophages in lung airways. Histological examination of lung tissue in animals challenged with a single chromate exposure revealed an increase in bronchiolar cell apoptosis and mucosal injury. Furthermore, chromate exposure induced injury and inflammation that progressed to alveolar and interstitial pneumonitis. Finally, a single Cr(VI) challenge resulted in a rapid and persistent increase in the number of airways immunoreactive for phosphorylation of the survival signaling protein Akt, on serine 473. These data illustrate that chromate induces both survival signaling and an inflammatory response in the lung, which we postulate may contribute to early oncogenesis.

Oxidative Stress Markers and Histological Analysis in Diverse Organs from Rats Treated with a Hepatotoxic Dose of Cr(VI): Effect of Curcumin

“…The resulting excessive production of ROS may lead to oxidative damage to deoxyribonucleic acid (DNA), lipids, and proteins. It has been reported that Cr(VI) compounds may induce injury to brain [26], heart [27], lungs [28], kidneys [29,30], spleen [31], pancreas [32], gastrointestinal system [33], and other vital organs [34] depending on dose level, schemes of treatment, and route of administration [35,36].…”

“…Tsapakos et al [56] observed low levels of strand break in rat lung after intraperitoneal injection of sodium dichromate (20 mg/kg b.w.) 1 h after injection; however, no strand breaks remained by 24 or 36 h. Moreover, animals exposed intranasallly [28] or intratracheally [57] to particulate Cr(VI), presented injury, inflammation, and a significant elevation of the mutation frequency in the lung. Chorvatovicova et al [58] injected K 2 Cr 2 O 7 (12 mg/kg b.w.)…”

Evaluation of Hexavalent Chromium Extraction Method EPA Method 3060A for Soils Using XANES Spectroscopy

“…This future work would be of particular importance in the case of environmental studies dealing with the toxicity of Cr(VI), which may concern easily extractible Cr(VI) but also more insoluble phases. 40,41 ' ASSOCIATED CONTENT b S Supporting Information. Figures S1ÀS3.…”

Luteolin inhibits Cr(VI)-induced malignant cell transformation of human lung epithelial cells by targeting ROS mediated multiple cell signaling pathways

“…Repetitive exposure to Cr(VI) results in persistent inflammation, and such an inflammatory microenvironment can further promote lung carcinogenesis (Beaver et al , 2009a; Beaver et al , 2009b). Cyclooxygenase-2 (COX-2) is a key enzyme in the conversion of arachidonic acid to prostanoids, and its activation is associated with inflammation and carcinogenesis (Hakozaki et al , 2014).…”