P3203 - Lipoic Acid Effects on Caco-2 Intestinal Epithelial Barrier Function

Katherine M. DiGuilio, DO, Elizabeth A. Del Rio, MS, Rocco Spadea, BS, Mary C. Valenzano, BS, James M. Mullin, PhD
Lankenau Institute for Medical Research, Wynnewood, PA

Introduction: Select micronutrients such as zinc, Vitamin D and quercetin have demonstrated ability to improve GI epithelial barrier function. Alpha-Lipoic acid (ALA), a micronutrient coming into extensive clinical use in neurological disease and the blood brain barrier, was tested here for its ability to improve and protect the GI barrier.

Methods: The Caco-2 human intestinal cell culture was the model used here. Epithelial barrier function was assessed by measuring transepithelial electrical resistance (TER) and transepithelial permeability of ¹⁴C-D-mannitol. Tight junctional proteins were analyzed by PAGE and Western immunoblot, as was the signaling intermediate, pERK.

Results: 200 μM ALA induced a 75% increase of TER at 24 hrs, the maximal concentration and duration of exposure. This ect was however not accompanied by any change in the permeability of the non electrolyte, D-mannitol. This increase in TER may have been transduced by a 15-20% significant decrease in the levels of the tight junctional proteins, Claudin-2 and Claudin-3. Claudins -1, -4 and -5 were unaffected. A 35% significant increase in short circuit current was also observed. Unlike the reported effects of other micronutrients on Caco-2 barrier function, this action of ALA did not involve the ERK pathway, based on a lack of effect on pERK levels, and a lack of additivity regarding effects of ALA and the ERK inhibitor, U0126, on TER. ALA was also able to reduce the severity of barrier leak caused by the proinflammatory cytokine, TNF-α.

Discussion: In light of reported positive effects of ALA on blood brain barrier leak, and neurological pathology generally, it is noteworthy that ALA may also reduce GI barrier leak, given the known role of GI barrier leak in systemic inflammation and the Gut-Brain Axis generally.


Disclosures:


Katherine M. DiGuilio, DO, Elizabeth A. Del Rio, MS, Rocco Spadea, BS, Mary C. Valenzano, BS, James M. Mullin, PhD. P3203 - Lipoic Acid Effects on Caco-2 Intestinal Epithelial Barrier Function, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.