BACKGROUND & AIMS: Our previous studies have provided evidence that p38 mitogen-activated protein kinase (MAPK) is involved in total parenteral nutrition (TPN)-associated complications, but its exact effects and mechanisms have not been fully understood. This study aimed to evaluate the roles of p38 MAPK inhibitor SB203580 in the TPN-induced loss of intestinal barrier function and liver disease. METHODS: A rodent model of TPN was used to analyze the roles of SB203580 in TPN-associated complications.Intestinal barrier function was evaluated by transepithelial electrical resistance (TER) and paracellular permeability in Caco-2 cells. The palmitic acid (PA) was used to induce hepatic lipoapoptosis in vitro. The lipoapoptosis was detected using Caspase-3/7 and lipid staining. RESULTS: In the present study, we showed that SB203580 treatment significantly suppressed TPN-mediated intestinal permeability in rats. SB203580 treatment significantly inhibited IL-1β-induced an increase in tight junction permeability of Caco-2 cells via repressing the p38/ATF-2 signaling. Unexpectedly, SB203580 treatment enhanced hepatic lipoapoptosis in the model of TPN. Palmitic acid (PA)-induced hepatic lipoapoptosis in human liver cells was significantly augmented by the SB203580 treatment. CONCLUSIONS: We demonstrate that the p38 MAPK inhibitor SB203508 ameliorates intestinal barrier function but promotes hepatic lipoapoptosis in model of TPN.
BACKGROUND & AIMS: Our previous studies have provided evidence that p38 mitogen-activated protein kinase (MAPK) is involved in total parenteral nutrition (TPN)-associated complications, but its exact effects and mechanisms have not been fully understood. This study aimed to evaluate the roles of p38 MAPK inhibitor SB203580 in the TPN-induced loss of intestinal barrier function and liver disease. METHODS: A rodent model of TPN was used to analyze the roles of SB203580 in TPN-associated complications.Intestinal barrier function was evaluated by transepithelial electrical resistance (TER) and paracellular permeability in Caco-2 cells. The palmitic acid (PA) was used to induce hepatic lipoapoptosis in vitro. The lipoapoptosis was detected using Caspase-3/7 and lipid staining. RESULTS: In the present study, we showed that SB203580 treatment significantly suppressed TPN-mediated intestinal permeability in rats. SB203580 treatment significantly inhibited IL-1β-induced an increase in tight junction permeability of Caco-2 cells via repressing the p38/ATF-2 signaling. Unexpectedly, SB203580 treatment enhanced hepatic lipoapoptosis in the model of TPN. Palmitic acid (PA)-induced hepatic lipoapoptosis in human liver cells was significantly augmented by the SB203580 treatment. CONCLUSIONS: We demonstrate that the p38 MAPK inhibitor SB203508 ameliorates intestinal barrier function but promotes hepatic lipoapoptosis in model of TPN.
Authors: Michael P Madaio; Istvan Czikora; Nino Kvirkvelia; Malgorzata McMenamin; Qiang Yue; Ting Liu; Haroldo A Toque; Supriya Sridhar; Katherine Covington; Rabei Alaisami; Paul M O'Connor; Robert W Caldwell; Jian-Kang Chen; Matthias Clauss; Michael W Brands; Douglas C Eaton; Maritza J Romero; Rudolf Lucas Journal: Kidney Int Date: 2019-03-21 Impact factor: 18.998
Authors: Pan Xu; Elhaseen Elamin; Montserrat Elizalde; Paul P H A Bours; Marieke J Pierik; Ad A M Masclee; Daisy M A E Jonkers Journal: Sci Rep Date: 2019-02-14 Impact factor: 4.379
Authors: Kristie Stefanoska; Josefine Bertz; Alexander M Volkerling; Julia van der Hoven; Lars M Ittner; Arne Ittner Journal: Sci Rep Date: 2018-09-24 Impact factor: 4.379