18ß-Glycyrrhetinic acid altered the intestinal permeability in the human Caco-2 monolayer cell model.

PURPOSE: Glycyrrhizin (GL) and its metabolites 18α-glycyrrhetinic acid (18α-GA) and 18ß-glycyrrhetinic acid (18ß-GA) are used as traditional medicine and food sweeteners. As the major rout of their administration is oral way, therefore their impact on intestinal epithelial cells are investigated. METHODS: The effects of GL and its metabolites on cell viability using MTT assay, on cytotoxicity using LDH release, on integrity of intestinal epithelial cells by measuring the transepithelial electrical resistance (TEER) and Luciferase permeability tests, on the expression of tight junction proteins at mRNA and protein level by qPCR and western blot techniques, and ultimately on the rate of test compounds absorption via Caco-2 cells monolayer were investigated. RESULTS: MTT assay showed a concentration- and time-dependent decrease in metabolic activity of Caco-2 cells induced by GL, 18α-GA, and 18ß-GA, while only 18ß-GA increased the LDH leakage. The monolayer integrity of Caco-2 cells in TEER assay only was affected by 18ß-GA. The permeability of paracellular transport marker was increased by 18α-GA and 18ß-GA and not GL. In transport studies, only metabolites were able to cross from Caco-2 cells monolayer. qPCR analyses revealed that 18ß-GA upregulated the expression of claudin-1 and -4, occludin, junctional adhesion molecules and zonula occludens-1, while 18α-GA upregulated only claudin-4. The expression of claudin-4 at protein level was downregulated non-significantly at 50 µM concentration of 18ß-GA. CONCLUSION: Our results suggest that 18ß-GA may cause cellular damages at higher concentrations on gastrointestinal cells and requires a remarkable attention of the nutraceutical and pharmaceutical industries.

Cardioprotective Effects of Atorvastatin Are Mediated Through PPARγ in Paraquat-Exposed Rats.

BACKGROUND: Paraquat poisoning is one of leading intoxication worldwide without an effective antidote and treatment protocol. Among the other organs, cardiotoxicity of paraquat has been frequently reported. AIM: The protective effects of atorvastatin (STN) on paraquat-induced cardiotoxicity and the role of peroxisome proliferator-activated receptors γ in the mediation of STN effects were investigated. METHODS: Forty-two male Wistar rats were aliquoted into control or test groups. The animals in test groups in addition of paraquat received saline normal (PQ), pioglitazone (PGT), atorvastatin (STN), PGT + STN, PGT + GW9662, and/or STN + GW9662 for 14 days. RESULTS: PGT and STN lowered lipid peroxidation rate, nitric oxide concentration, and activity of myeloperoxidase and CK/MB in the heart. PGT and STN protected from thiol molecules reduction and PQ-induced histopathological injuries. STN regulated the PQ-induced upregulation of COX-II expression in the heart. All STN-related protective effects were reversed by GW9662 as PPARγ antagonist. CONCLUSIONS: These data suggest a cardioprotective effect for STN against the PQ-induced inflammation and oxidative stress. The pharmacologic approach of these findings indicates that STN through PPARγ pathway lowered the PQ-induced cardiotoxicity.