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

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.

Toxic Mechanisms of Five Heavy Metals: Mercury, Lead, Chromium, Cadmium, and Arsenic

“…Furthermore, after 24, 48, 72, and 96 h after treatment DNA damage was observed in a dose- and time-dependent manner ( Patlolla et al, 2009 ). Salama et al (2016) showed a high risk of brain damage in low doses of Cr on Albino Wistar rats via intranasal exposure. Moreover, higher Cr concentrations caused lung injury.…”

“…Moreover, higher Cr concentrations caused lung injury. A 2 mg/kg intranasal potassium dichromate resulted in the elevation of oxidative stress biomarkers: interleukin-1β (IL-1β), phosphorylated protein kinase B (PKB), and cyclooxygenase 2 (COX-2) ( Salama et al, 2016 ).…”

Haematococcus pluvialis Carotenoids Enrich Fractions Ameliorate Liver Fibrosis Induced by Thioacetamide in Rats: Modulation of Metalloproteinase and Its Inhibitor

“…At the end of the experiment, rats were anesthetized with pentobarbital sodium. Blood samples were withdrawn from the retro-orbital plexus of the rats under the same anesthesia; then, rats were sacrificed by decapitation [ 33 ] under the same anesthesia for the collection of liver samples. A 0.5 gm of the liver of each animal was rapidly dissected out, washed, and homogenized using phosphate-buffered saline (PBS, 50 mM potassium phosphate, pH 7.5) at 4°C to produce a 20% homogenate using a homogenizer (Heidolph, DIAX 900, Germany).…”

Promising Antidiabetic and Antimicrobial Agents Based on Fused Pyrimidine Derivatives: Molecular Modeling and Biological Evaluation with Histopathological Effect

“…Organ tissues were fixed in 10% buffered formalin, processed through ascending grades of alcohol, cleared in xylene and prepared into paraffin blocks. Serial sections 5 microns thick were prepared from each block and stained with haematoxylin and eosin for rou-tine histopathologic study [37,38]. The sections were examined under a CX41 research microscope (Olympus, Center Valley, PA, USA) at the National Research Centre Pathology Department.…”