Research Article: Intranasal Chromium Induces Acute Brain and Lung Injuries in Rats: Assessment of Different Potential Hazardous Effects of Environmental and Occupational Exposure to Chromium and Introduction of a Novel Pharmacological and Toxicological Animal Model

Date Published: December 20, 2016

Publisher: Public Library of Science

Author(s): Abeer Salama, Rehab Hegazy, Azza Hassan, Osama Ali Abulseoud.

http://doi.org/10.1371/journal.pone.0168688

Abstract

Chromium (Cr) is used in many industries and it is widely distributed in the environment. Exposure to Cr dust has been reported among workers at these industries. Beside its hazardous effects on the lungs, brain injury could be induced, as the absorption of substances through the nasal membrane has been found to provide them a direct delivery to the brain. We investigated the distribution and the effects of Cr in both brain and lung following the intranasal instillation of potassium dichromate (inPDC) in rats. Simultaneously, we used the common intraperitoneal (ipPDC) rat model of acute Cr-toxicity for comparison. Thirty male Wistar rats were randomly allocated into five groups (n = 6); each received a single dose of saline, ipPDC (15 mg/kg), or inPDC in three dose levels: 0.5, 1, or 2 mg/kg. Locomotor activity was assessed before and 24 h after PDC administration, then, the lungs and brain were collected for biochemical, histopathological, and immunohistochemical investigations. Treatment of rats with ipPDC resulted in a recognition of 36% and 31% of the injected dose of Cr in the brain and lung tissues, respectively. In inPDC-treated rats, targeting the brain by Cr was increased in a dose-dependent manner to reach 46% of the instilled dose in the group treated with the highest dose. Moreover, only this high dose of inPDC resulted in a delivery of a significant concentration of Cr, which represented 42% of the instilled dose, to the lungs. The uppermost alteration in the rats locomotor activity as well as in the brain and lung histopathological features and contents of oxidative stress biomarkers, interleukin-1β (IL-1β), phosphorylated protein kinase B (PKB), and cyclooxygenase 2 (COX-2) were observed in the rats treated with inPDC (2 mg/kg). The findings revealed that these toxic manifestations were directly proportional to the delivered concentration of Cr to the tissue. In conclusion, the study showed that a comparably higher concentrations of Cr and more elevated levels of oxidative stress and inflammatory markers were observed in brain and lung tissues of rats subjected to inPDC in a dose that is just 0.13 that of ipPDC dose commonly used in Cr-induced toxicity studies. Therefore, the study suggests a high risk of brain-targeting injury among individuals environmentally or occupationally exposed to Cr dust, even in low doses, and an additional risk of lung injury with higher Cr concentrations. Moreover, the study introduces inPDC (2 mg/kg)-instillation as a new experimental animal model suitable to study the acute brain and lung toxicities induced by intranasal exposure to Cr compounds.

Partial Text

The wide environmental distribution of chromium (Cr) leads to an increased interest of its toxicity and biological effects. Cr exists mainly in two states, the trivalent (CrIII) and hexavalent (CrVI); both are used in various industrial activities such as steel works, metal finishing, petroleum refining, Cr electroplating, and leather tanning [1, 2].

The goal of this study was to use a rat model to evaluate the potential brain and lung injuries among individuals environmentally or occupationally exposed to Cr dust. However, in the study, intranasal instillation of PDC was used as an alternative to inhalation of Cr-dust; this is to avoid the downsides of inhalation, and to provide a more accurate control of the exposure concentration. Other research group used the intratracheal rout instead of inhalation for the same reasons [24]. However, in our study we used the intranasal instillation rather than intratracheal to assess, precisely, the effect of passing Cr through the nasal cavity, and to explore its potential absorption through the intranasal mucosa.

In conclusion, the study showed that a comparably higher concentrations of Cr and more elevated levels of oxidative stress and inflammatory markers were observed in brain and lung tissues of rats subjected to inPDC in a dose that is just 0.13 that of ipPDC dose commonly used in Cr-induced toxicity studies. Therefore, the study proposes a high risk of brain-targeting injury among individuals environmentally or occupationally exposed to Cr dust, even in low doses, and an additional risk of lung injury with higher Cr concentrations. Therefore, some recommendations must be needed for practitioners of occupational and environmental medicine to be alert for the brain and lung hazards of exposure to Cr dust, and routine physical examinations are needed to assess and inhibit these toxic effects. Besides, further studies are required to find suitable protective and therapeutic agents against these Cr-induced toxicities. Our study suggests neuroprotective agents with anti-inflammatory and anti-oxidant properties as potential candidates.

 

Source:

http://doi.org/10.1371/journal.pone.0168688