Comparative Study of Molecular Mechanisms of Skin Irritation After Acute Exposure to m-XYLENE in Rats and Guinea Pigs
Interim rept. Mar 2000-Jul 2001
WRIGHT STATE UNIV DAYTON OH DEPT OF PHARMACOLOGY AND TOXICOLOGYY
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Organic solvents like xylene are recognized as skin irritants 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 pigs skin to xylene irritation, since these species differ in their response to other chemicals. We also determined which animal model was more appropriate for predicting xylene-induced skin irritation. Animals were exposed to m-xylene 250 ul on their shaved back for lhr using Hill Top Chambers. Zero, one, three and five hrs after the exposure, treated and sham treated skin samples 1g were collected, homogenized with Tris buffer and measured for early markers of skin irritation. Western blot analysis revealed that IL-1 alpha protein levels increased 3-fold more in rats than in guinea pigs within one hr after xylene exposure. In contract, iNOS protein induction was four-fold greater in guinea pigs that in rats. In rats, the changes in iNOS levels were comparable to the changes in IL-1 alpha levels but occurred two hours later. NO levels, determined by Griess reagent, were elevated four-fold within two hours after the beginning of the xylene exposure in rats. However, in guinea pigs, only a slight change of NO level was observed. immunohistochemical staining of skin sections using specific antibodies showed immunopositive cells for IL-1 alpha and iNOS. Both antibodies were more predominant in the epidermis of guinea pigs than rats. In addition, oxidant species formation detected using DCF-DA was increased over the controls by xylene exposure after 1 hour. As with oxidative species and other early molecular events, histology sections in the guinea pigs revealed more damage and cellular infiltration compared to rats.
- Anatomy and Physiology
- Organic Chemistry