The HIV protease inhibitors saquinavir, ritonavir, and nelfinavir induce apoptosis and decrease barrier function in human intestinal epithelial cells.

摘要: Background and aims: Diarrhoea is a frequent adverse effect of HIV protease inhibitors (PIs) which may be due to intestinal barrier disruption. We investigated whether tight junction dysregulation, apoptosis or necrosis are responsible for this epithelial damage. Methods: Saquinavir, nelfinavir, ritonavir were added the mucosal serosal side HT-29/B6 colon cell monolayers. Transepithelial resistance was monitored 72 h assess function. Apoptosis by light electron microscopy quantified nucleosome ELISA LDH measurement, respectively. Tight components analysed Western blots occludin zonula occludens. induction in normal human epithelium examined measurement poly(ADP-ribose) polymerase (PARP) cleavage tissue explants cultured with PIs 24 h. Results: decreased transepithelial more than 44% Histology revealed massive apoptotic body formation but no evidence after PI treatment. Correspondingly, release lower 0.2%/h total LDH, independent treatment, nucleosomes increased up 22-fold drug treatment versus control. Occludin occludens-1 expression membrane not diminished. PARP treated PIs. Conclusions: PI-induced disruption cells alterations, lead leak-flux diarrhoea vivo. Our findings suggest that could have potential antitumour therapy.