Molecular mechanism of skin irritation after acute exposure to m-xylene in rats and guinea pigs.
Gunasekar-PG; Kabbur-MB; Rogers-JV; Garrett-CM; McDougal-JN
Toxicologist 2001 Mar; 60(1):59
Organic solvents like xylene are recognized as a skin irritant after dermal exposure. The molecular responses to organic solvents that result in acute irritation are not understood. In the present study, we compared and quantified the molecular responses of rat and guinea pig skin to xylene irritation, since these species differ in their response to other chemicals. Animals were exposed to m-Xylene (250 ul) on their shaved back fur 1hr using Hill Top Chambers. Zero, one, three and five hrs after the exposure treated and sham treated skin samples (1g) were collected and homogenized with Tris buffer. Supernatants were used to measure the early markers of skin irritation. Western blot analysis revealed that IL-1 protein levels increased 3 fold more in rats than in guinea pigs within one hr after xylene exposure. In contrast, iNOS protein induction was four-fold greater in guinea pigs than in rats. In rats the changes in iNOS levels were comparable to the changes in IL-1 levels but occurred two hours later. NO levels, determined by Griess reagent, were elevated four fold two hours after the beginning of the xylene exposure in rats. However, in guinea pigs, only a slight change of NO level was observed. In addition, immunohistochemical localization revealed that immunopositive cells for IL-1 and iNOS were detected more predominandy in the epidermis of guinea pig skin than in rat. An oxidant-sensitive fluorescence dye, DCFDA was used as a probe to detect free radical generation in order to compare the intensity of oxidative stress formed due to xylene exposure in these species. These results suggest that the skin's molecular and biological response to xylene exposure occur earlier in guinea pigs than in rats.
Dermatitis; Dermatosis; Occupational-exposure; Exposure-levels; Occupational-diseases; Medical-treatment; Mathematical-models; Skin-exposure; Skin-irritants; Pharmacodynamics; Xylenes; Laboratory-animals; Animal-studies; Animals; Histopathology; Organic-chemicals; Solvents; Acute-exposure; Exposure-assessment; Antibody-response
Disease and Injury: Allergic and Irritant Dermatitis
The Toxicologist. Society of Toxicology 40th Annual Meeting, March 25-29, 2001, San Francisco, California
Wright State University, Dayton, Ohio