Attenuation by l-thyroxine of oxidant-induced gut epithelial damage

Document Type: Original Article


1 Department of Physiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

2 Department of Microbiology & virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran


Objective(s): Severe injuries are often associated with tissue hypothyroidism, elevated damaging mediators in circulation, and broken gut epithelial barrier.  However, the relationships between the hypothyroid state and gut epithelial damage are largely unknown.  Therefore, in this study, we investigated the effects of L-thyroxine (T4) on in vitro models of intact and compromised gut epithelium.
Materials and Methods: Gut epithelium equivalent was generated by cultivation of IEC-18 rat intestinal epithelial cells into transwell inserts. Confluent cultures were then compromised by scratching or H2O2 and traumatized rat sera (TUR sera) treatments.  Macromolecules permeation and transepithelial electrical resistance (TEER) were evaluated by conventional methods. Morphology and scratch wound closure were assessed microscopically. Cell viability/proliferation was assessed by MTT assay.
Results: Both H2O2 and TUR sera induced marked yet different types of epithelial disintegration.  While H2O2 significantly increased and decreased probe permeation and TEER, respectively, TUR sera was ineffective.  Cultures treated with normal rat sera (sham sera) exhibited morphology, probe permeation, and TEER comparable to those of control cultures.  Presence of T4 attenuated the H2O2-induced but not TUR sera-induced damages. T4 treatment accelerated, albeit marginally, wound closure but had virtually no effects on cell viability/proliferation.  
Conclusion: These data suggest that different mechanisms are involved in oxidant- and trauma-induced gut epithelial barrier breakdown.  Besides, they show that T4 markedly attenuates oxidant-induced gut epithelial damage.  Accordingly, one may also conclude that tissue hypothyroidism does not contribute to trauma-induced gut barrier breakdown.


Main Subjects

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