HISTOPATHOLOGICAL ANALYSIS OF THE F344 RAT LUNG UPON EXPOSURE TO RETENOIC ACID, OVALBUMIN, MOLD SPORES AND CITRAL.

The paradoxical role of retinoic acid (All Trans Retinoic Acid; ATRA) in the development of allergic and/or inflammatory complications in contrast to a therapeutic modality for lung pathology is not well understood or established in the literature. As well, the role of Citral (inhibitor of retinoid function; a non-toxic chemical that exists in two forms (diethyl; C1 or cis-trans dimethyl; C2), in the reversal of retinoic acid, ovalbumin and allergic mold spore pathophysiology is also not well ascertained under an in vivo setting. Therefore, it is hypothesized that exposure of F344 lung tissues to supra-physiologic levels of retinoic acid, ovalbumin and mold spores individually or in combination with each other will lead to inflammatory tissue pathology and that Citral 1 and 2 will reverse or ameliorate the related pathological damage to lung tissues. Even though ovalbumin and retinoic acid have been previously applied through intra-tracheal route in cancer prevention and immunological research, the objective of this study was to evaluate the histopathological implications of such exposure in vivo. This IACUC approved in vivo study used Fischer 344 rats ( n = 80 ; 229 to 273g), which were randomly assigned to controls as well as ovalbumin and mold-sensitized treatment groups (0.80 mg/kg and 1×109 mold spores combined from 4 strains/100 μl intra-tracheal; all others were dosed by intra-peritoneal injection at days 1 and 7 with 80 mg/kg each of ATRA as well as 20 and 50 mg/kg each of Citrals 1 or 2 individually or in combination to represent all four chemicals and mold spores treatments. Positive and negative controls for each treatment were also included in the study. Animals were housed in rat cages at the JSU Research Animal Core Facilities and were placed on a 12:12 light-dark cycle. A standard rodent diet and water access were provided ad libidum. All animals were sacrificed on day 21 and lung tissues were processed for histopathology. Slides were prepared and were digitized for comparison of tissues pathology. Results showed that exposure of the F344 rats to ovalbumin and ATRA showed various levels of lung tissue damage that was ameliorated by Citral 2 in combination. Mold and ATRA exposure caused various levels of lung tissue damage that was reversed by C1 in combination with each other. Taken together, the study showed that there are variable pathologic inflammatory responses from the interaction of ovalbumin, Citrals, mold spores and retinoic acid, and that the addition of Citrals have reversed lung tissue pathologies. These findings warrants further investigation as to the actual role of these interactions in relation to acute/chronic lung disease and the possibility of reversing retinoid-mediated pathologies in the Fisher rat model.