Effects of conventional and alternative asthma therapies on the GIT and heart in an experimental model of murine asthma

Abstract

Asthma is a worldwide pathology defined commonly as a chronic inflammatory syndrome of the lungs and airways. Unfortunately our current understanding of this inflammatory syndrome is limited, especially in terms of its extra-respiratory effects. It has been hypothesized within scientific literature, and even shown in a limited number of studies, that asthma has a detrimental effect upon the digestive and circulatory systems of the body, although the extent of this effect is still unclear. Asthma has been implicated in determinantal digestive system events through the diseases use of the common mucosal immune system, believed to connect the mucosal immune systems of the digestive and respiratory tracts. The circulatory system has been linked to asthma due to the ill-defined dependence on respiratory functions. The aims of this study were threefold. Firstly, to explore the morphological impart of asthma on the digestive tract and heart using the BALB/c asthmatic murine model. Secondly, compare and correlate the findings of this study with existing literature and thirdly, assess the efficiency of a varietly of therapeutic models (hydrocortisone, a conventional asthma therapy, and Modul8TM, a homeopathic immunomodulator employed as an asthma remedy) on the two organ systems in question. The employed asthmatic murine model was established by sensitizing and nebulizing six-week old female BALB/c mice with ovalbumin and subsequently treating two of the three asthmatic mice groups with various asthma therapies. The model was run over a period of 43 days, after which the mice were terminated. Blood smears and extracted bronchoalveolar lavage fluid acquired at termination from these mice, compared to equivalently terminated control BALB/c mice housed under the same conditions for the same period of time, showed that the untreated mice clearly developed asthma, due to a significant increase in their circulating and infiltrating eosinophil levels. The use of both treatments showed equivalent abilities to reduce the rodents circulating and infiltrating eosinophil levels back to control levels, showing both treatments efficiencies in combating asthma. Tissue sections were removed from the duodenum of the small intestine, colon of the large intestine, fundus and pylorus of the stomach as well as the hearts right ventricle from each of the terminated mice and prepared for light, transmission electron and scanning electron microscopic evaluation, except in the case of the heart tissue sections where scanning electron microscopy was not employed. The various forms of microscopic evaluation upon the untreated asthmatic mice and subsequent comparison to corresponding control tissues of the gastrointestinal tract revealed that asthma induced various morphological alterations, although far fewer in comparison to what has been described in literature for human asthmatics. The duodenum of the small intestine underwent increased leukocyte infiltration, fibrosis and villous atrophy, all of which has been noted amongst human asthmatics, while the colon of the large intestine appeared to undergo fibrosis under asthmatic conditions, as of yet not described in scientific literature. The stomach did not show any theoretically expected morphological alterations but the fundic and pyloric chief cells were shown to undergo hypersecretion, while the fundic and pyloric parietal cells were shown to undergo hypertrophy. Neither the hypersecretion nor the hypertrophy seen in the stomach has thus far been described in literature. Evaluation of hydrocortisone and Modul8TM’s effects under asthmatic conditions within the corresponding regions of the gastrointestinal tract showed that both treatments were equally effective in suppressing, often back to control levels, the asthma induced intestinal pathologies, except in the case of large intestinal fibrosis where Modul8TM did not appear to have an effect, but tended to aggravated the gastric associated pathologies, particularity when considering hydrocortisone. Light and transmission electron microscopic evaluation of the right ventricles cardiac fibres of the untreated asthmatic mice showed no theoretically expected or practically visible, in comparison to the control mice, morphological alterations under the disease although they did show an increased mitochondrial size which may indicate increased heart strain. Neither hydrocortisone nor Modul8TM appeared able to correct this morphological alteration. In totality it was concluded that asthma did clearly induce pathological alterations within extra-respiratory systems – specifically the gastrointestinal tract and heart of the employed BALB/c asthmatic murine model. The model provided novel morphological alterations, under asthmatic conditions – colonic fibrosis, stomach chief cell hypersecretion, stomach parietal cell hypertrophy and right heart ventricle mitochondrial expansion – providing new avenues of research under the topic of asthmas extra-respiratory effects. Although the employed BALB/c asthmatic murine model did present novel pathologies, a better model should be sought for future studies which better correlates to the situation present by human asthmatics, thus far described in literature. Additionally, better medications which are able to treat, not only the respiratory but too the digestive and cardiac asthma associated alterations should be sought to help benefit and prevent unwanted aliments within asthmatics. At present Modul8TM, although not entirely beneficial when considering all its effects on the model, would appear to a better treatment option in comparison to hydrocortisone for asthma and its variously induced bodily pathologies.