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.

IMPACT OF ATRA ON OVALBUMIN AND MOLD-SENSITIZED F344 RATS AND REVERSAL OF HEALTH-RELATED IMPLICATIONS BY CITRAL.

The role of retinoic acid (All Trans Retinoic Acid; ATRA) in the development of hypervitaminosis A pathophysiology 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 pathophysiological implications is also not ascertained under an in vivo setting. Therefore, it is hypothesized that ovalbumin exposure will sensitize the body to supra-physiologic levels of retinoic acid leading to a negative pathophysiological impact and that Citrals 1 and 2 will reverse or ameliorate the related damage to the body's pathophysiology. Even though ovalbumin and retinoic have been previously applied through intra-tracheal route in cancer prevention and immunological research, the objective of this study was to evaluate their interaction as a remedy for hypervitaminosis A. 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 1X109 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. Rat weights were recorded on day 1 and 21, all animals were sacrificed on day 21 and blood was collected and processed for hematological parameters. Results showed that even though C1 and C2 were not toxic individually, their combination at high dosing was lethal. Exposure of ovalbumin-sensitized rats to ATRA showed various levels of weight losses and negative hematological implications that were ameliorated by exposure to Citrals at various combinations with retinoic acid. Taken together, the study showed that there are variable pathophysiological responses from the interaction of ovalbumin, mold spores and retinoic acid and that Citrals were found to be individually effective in reversing health-related pathophysiologies. These findings warrants further investigations as to the actual role of these interactions in relation to acute pathophysiologic health implications and the possibility of reversing hypervitaminosis A-mediated health-related impacts.

Impact of Triple Combinations of Retinoic Acid, Mold Spores and Citral on the F344 Rat Lung Tissue Pathology.

The impact of retinoic acid (All Trans Retinoic Acid; ATRA) and Mold spores (MLD) in the development of lung pathology and in vivo tissue remodeling have not been well established in the literature. In addition, the role of citral (inhibitor of retinoid function) in the improvement of lung pathology has not been ascertained in animal studies. Therefore, it is hypothesized that ATRA and Mold (MLD) exposure will sensitize lung tissues leading to lung tissue pathology and that Citrals (C1 and C2) will reverse, ameliorate or improve the associated pathological damage to lung tissues. The study used an IACUC approved between-subject in vivo randomized split plot factorial design (F344 rat model; N=40). Animals were exposed to seven different treatments including untreated control, MLD, ATRA, Citrals (C1 and C2) and their MLD combinations (MLD+ ATRA+ C1, and MLD+ ATRA+ C2) by intra-peritoneal route. Rat weight and blood data were collected on Days 1 and 21, all animals were sacrificed on day 21, and lung tissues were processed for histopathology. Results from weight and blood data (ANOVA and Duncan) as well as from histopathological analyses supported the findings that exposure of F344 rats to MLD combinations with ATRA and Citrals showed various levels of lung tissue damage that were impacted by either C1 or C2 exposure. This promising study showed impressive responses on the interaction of MLD, Citrals, and ATRA as related to their impact on associated lung tissue pathologies.

Health Impact of Retinoic Acid (ATRA) on Ovalbumin-Sensitized F344 Rat Lung and Improvement of Tissue Pathology by Citral.

The health impact of retinoic acid (All Trans Retinoic Acid; ATRA) in the development of lung pathology and tissue remodeling has not been well established in the literature. Equally, the role of Citral (inhibitor of retinoid function) in the improvement of lung pathology has not been ascertained in vivo. Therefore, it is hypothesized that ATRA and Ovalbumin (Egg albumin; OVA) exposure will sensitize lung tissues leading to lung tissue pathology and that citrals (C1 and C2) will reverse or ameliorate the related pathological damage to lung tissues. The study used an IACUC approved between-subject in vivo randomized split plot factorial design (F344 rat model; N=35). Animals were sensitized to OVA and then exposed to six different treatments; negative control (-ve), ATRA, Citrals (C1 and C2) and their triple combinations (OVA+ ATRA + C1, OVA+ ATRA + C2), by intra-peritoneal route. Rat weight data and blood were collected on Days 1 and 21, all animals were sacrificed on day 21, and lung tissues were processed for histopathology. Results from rat weights and blood (ANOVA and Duncan) as well as from the histopathological analysis of exposing the F344 rats to OVA in combinations with ATRA and citrals, revealed various levels of lung tissue damage that was impacted by exposure to citral. We conclude that OVA+ATRA+C1 combination treatment did improve lung pathology as compared to single individual treatments. However, the OVA+ATRA+C2 combination not only failed to improve these parameters, but even worsened the lung pathology of this model. This promising study showed variable responses on the interaction of Ovalbumin, citrals, and ATRA as related to their damage/improvement of related lung tissue pathologies.

The Negative Impact of Combining Retinoic Acid (ATRA) and Mold Spores on F344 Rat Lung and Improvement of Tissue Pathology by Citral.

The impact of retinoic acid (All Trans Retinoic Acid; ATRA) and Mold spores (MLD) in the development of lung pathology and in vivo tissue remodeling have not been well established in the literature. In addition, the role of citral (inhibitor of retinoid function) in the improvement of lung pathology has not been ascertained in animal studies. Therefore, it is hypothesized that ATRA and Mold (MLD) exposure will sensitize lung tissues leading to lung tissue pathology and that Citrals (C1 and C2) will reverse, ameliorate or improve the associated pathological damage to lung tissues. The study used an IACUC approved between-subject in vivo randomized split plot factorial design (F344 rat model; N=40). Animals were exposed to eight different treatments including vehicle, MLD, ATRA, Citrals (C1 and C2) and their MLD combinations (MLD+ ATRA, MLD+ C1, and MLD+ C2) by intra-peritoneal route. Rat weight and blood data were collected on Days 1 and 21, all animals were sacrificed on day 21, and lung tissues were processed for histopathology. Results from weight and blood data (ANOVA and Duncan) as well as from histopathological analyses supported the findings that exposure of F344 rats to MLD combinations with ATRA and Citrals showed various levels of lung tissue damage that were impacted by either C1 or C2. This promising study showed impressive responses on the interaction of MLD, Citrals, and ATRA as related to their impact on associated lung tissue pathologies.

Experimental induction of lung damage in the f344 rat upon exposure to citral, retinoic Acid (atra), ovalbumin and mold spores.

The experimental impact of retinoic acid (All Trans Retinoic Acid; ATRA), citrals, ovalbumin and mold spores in the development of lung pathology and tissue remodeling are not well established in the literature. As well, the role of these agents in lung pathology was not ascertained under an in vivo setting. Therefore, it is hypothesized that citrals, ATRA, ovalbumin and mold-spore exposure will sensitize lung tissues and will lead to the development of lung tissue pathology in these animals. The study used an IACUC approved between-subject in vivo randomized split plot factorial design (F344 rat model; N=30). Mold spores were applied to animals by intra-tracheal route whereas vehicle, ovalbumin, C1, C2 and ATRA were administered by intra-peritoneal route. Rat weight data and blood were collected on Days 1 and 21. All animals were sacrificed on day 21 and lung tissues were processed for histopathology. Evidence from weights and blood (ANOVA and Duncan) as well as histopatholgical analysis supported the findings that exposure of these animals to C1, C2, ATRA, ovalbumin and mold spores showed different levels of lung tissue damage representing environmental exposure to these agents. This promising study showed variable lung tissue responses to the administration of ATRA, ovalbumin, citrals, and mold spores in the development of various levels of lung tissue pathologies.

Impact of supra-physiologic retinoids on ovalbumin-sensitized f344 lung tissue and reversal of related pathology by citral - biomed 2011.

The role of retinoids (All Trans Retinoic Acid; ATRA, and Retinyl Palmitate; RP) in the development of lung hypervitaminosis A pathology is not well understood or established in the literature. As well, the role of Citral (inhibitor of retinoid function) in the reversal of lung pathology is also not ascertained under an in vivo setting. Therefore, it is hypothesized that ovalbumin exposure will sensitize lung tissues to supra-physiologic levels of retinoids leading to tissue pathology and that Citral 1 and 2 will reverse or ameliorate the related pathological damage to lung tissues. Even though ovalbumin and retinoids have been previously applied through intra-tracheal route in cancer prevention and immunological research, the objective of this pilot study was to evaluate techniques, establish functional dosing and generate preliminary data before further experimentation. This IACUC approved in vivo study consist of twenty one (n = 21) Fischer 344 rats (200 to 400g) which were randomly assigned to controls and two ovalbumin-sensitized treatment groups (low; 0.15 mg/kg and high; 0.30 mg/kg, all sensitized by intra-peritoneal injection at day 1) and were also dosed at day 7 with 40 and 80 mg/kg each of ATRA or RP as well as 20 and 50 mg/kg each of Citrals 1 or 2 individually or in combination to represent low and high for all four chemicals, which were administered by intra-peritoneal injection. Citral is a non-toxic chemical that exists in two forms (diethyl; C1 or cis-trans dimethyl; C2). 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 adlibidum. Rat weights were recorded on Day 1 and 21, 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 even though C1 and C2 were not toxic individually, their combination at high dosing was lethal. As well, the combination of high dosing of RP and C1 was also lethal. Exposure of ovalbumin-sensitized rats to ATRA showed various levels of lung tissue damage that was not ameliorated by Citrals. RP exposure caused various levels of tissue damage that was not reversed by either C1 or C2. Taken together, the study showed that there are variable pathologic responses from the interaction of ovalbumin, Citrals and retinoids and those Citrals failed in reversing tissue pathologies. These findings warrants further investigation as to the actual role of these interactions in relation to chronic lung disease and the possibility of reversing retinoid-mediated pathologies in the Fisher rat model.