enac, piroxicam, metamizole or ibuprofen, each and every added at a concentration that elicited an identical degree of oxidative strain, proficiently prevented (by 846 ) the oxidative pressure induced by these agents. Even so, relative to its antioxidant efficacy, the protection afforded by OAE against the loss of TEER induced by these NSAIDs was hugely dissimilar, ranging from 18 (against piroxicam) to 73 (against indomethacin). Fuentes et al. [234] reported that, when correlating each protections, an R2 value of 0.087 was obtained, suggesting that the potential of Q-BZF to prevent the oxidative tension isn’t mechanistically associated to its–uneven and only limited–ability to defend the monolayers against the loss of barrier function induced by the former agents. Additionally, Fuentes et al. [234] observed that, in addition to inducing oxidative tension, the five NSAIDs have been in a position to induce, though to a distinct extent, the activation of the pro-oxidant and Cathepsin B Storage & Stability pro-inflammatory nuclear expression factor, nuclear element kappa B (NF-B) in monolayers of Caco-2 cells. Interestingly, even though OAE totally prevented the NF-B activation induced by indomethacin, it exerted no inhibitory effect on that induced by the 4 other NSAIDs, suggesting that the inhibition of NF-B activation will not be essential to prevent the enhance in TEER induced by the latter agents. Despite the fact that the activation of NF-B is often both a bring about plus a consequence of your genesis of ROS [246], inside the case of indomethacin, Mazumder et al. [247] recently reported that this NSAID activates the atypical zeta isoform of protein kinase C (PKC), which phosphorylates MAPK p38 [248], which in turn activates NF-B [249]. This nuclear issue may also be activated by distinctive PKC, and this activation could be mediated by ROS [250]. Because indomethacin-induced NF-B activation may be straight attributed to an ERK8 site increase in ROS or to an indirectly promoted PKC activation by the same species, the inhibition of NF-BAntioxidants 2022, 11,17 ofactivation by Q-BZF could either be attributed to a direct activation-inhibiting action on PKC or to an indirect ROS-removing action by means of Nrf2 activation. In line with the in vitro protection exerted by Q-BZF or by OAE against the elevated paracellular permeability of Caco-2 monolayers induced by indomethacin [234], the capacity of OAE to protect in vivo against the loss of intestinal barrier function induced by the same agent was not too long ago described in rats [251]. In their research, Fuentes et al. [251], assessing the intestinal permeability using the non-digestible probe 3-5-kDa dextran conjugated with fluorescein isothiocyanate (FITC dextran), observed that the oral administration of Q-BZF (80 /Kg body weight) as OAE fully abolished the 30-fold increase within the concentration of FITC dextran observed inside the serum of rats simultaneously provided indomethacin (40 mg/Kg body weight). This effect was found to become dose-dependent and largely conserved (by 85 ) when OAE was given 180 min prior to indomethacin. As previously observed by precisely the same authors in vitro [234], the in vivo observed intestinal barrier functionprotective effect of OAE was accompanied by a complete prevention on the NF-B activation and on the enhance inside the inflammatory parameters interleukine-8 and myeloperoxidase that are generally elevated within the duodenal mucosa of animals provided indomethacin [252,253]. It is actually noteworthy that OAE administration didn’t alter the basal intestinal mucosa NF-B levels in animals offered no indomethac
