Histopathological changes and expression of transforming growth factor beta (TGF-β3) in mice exposed to gliotoxin

Abstract

Background: Gliotoxin (GT) is the prototype of a class of epipolythiodioxopiperazines (ETPs) which are secondary metabolites made by fungi organisms only e.g., Aspergillus fumigatus, characterized by a disulfide bridge across a piperazine ring with low molecular weight (326 Da),and its sulphur bridge imparts all known toxicity of these molecules. Its name was derived from its identification as a metabolite of Gliocladium fimbriatum as it is previously isolated. It had histopathological effects of human and animals tissues and thus may alter the immune response. Objectives: The current study aimed to evaluate the effect of GT on immunological and histological changes in lung, liver, and kidney in addition to morphological changes in colon using animal models. Methodology: Mature male BALB/c mice were used in this study, animals were provided by Biotechnology researches center of Al-Nahrain University. To study the histological changes and expression of Transforming growth factor beta (TGF-β3) in mice, animals were injected intraperitoneally (i.p.) with acute dose of both sample and standard gliotoxin with control group (received i.p. one dose of methanol 10%) and the mice of each group were sacrificed at day seven, each mouse was dissected and the organs lung, liver and kidney were collected then sectioned. Mice of another groups were administrated with one dose of sample gliotoxin through the lumen of the colon using a vinyl catheter positioned 5 cm from the anus, and the control group received methanol 10%, the mice were killed on day seven of administration to study the morphological changes in the colon. Results: Gross-examination showed clear pathological changes in examined organs of mice treated intraperitoneally with gliotoxin (i.p.) injection during seven days, lesions were seen in examined organs with groups of all concentrations of both sample and standard gliotoxin in comparing with control. After intrarectal administration, many signs for mycotoxicosis were observed, like shivering, redness around the anus and bristling of hair. Although of the aggressive behavior of mice and loss of activity at the day 6 of treatment was also reduced. In both sample and standard GT groups, the elevation at the high concentrations of the gliotoxin gave over TGF-β3 expression in liver, lung, and kidney. Conclusions: It can be concluded that both of sample and standard gliotoxin showed the same effectiveness in vivo to induce histopathological changes and the immunohistochemical studies revealed that the increasing of TGF-β3 expression was in a significant relationship between the immunoreactive cell and its intensity with number and size of lesion in the same tissue at probability (P value) < 0.05 level, so further investigations are required to evaluate the acute and /or chronic effect of gliotoxin on other cytokines and further histopathological studies of acute and/or chronic effect of gliotoxin on other organs such as muscles, heart, brain, spleen and intestine are required. Keywords: Gliotoxin, Histopathological effect, TGF-β3, Immunohistochemical technique