Mechanisms underlying the hormetic effect of conjugated linoleic acid: Focus on Nrf2, mitochondria and NADPH oxidases.

Nuclear factor erythroid 2-related factor2 (Nrf2) is a redox-sensitive transcription factor. Its activation by low dietary intake of ligands leads to antioxidant effects (eustress), while pro-oxidant effects (oxidative distress) may be associated with high doses. NADPH oxidases (NOXs) and the mitochondrial electron transport chain are the main sources of intracellular ROS, but their involvement in the biphasic/hormetic activity elicited by Nrf2 ligands is not fully understood. In this study, we investigated the involvement of NOX expression and mitochondrial function in the hormetic properties of omega-3 typically present in fish oil (FO) and conjugated linoleic acid (CLA) in the mouse liver. Four-week administration of FO, at both low and high doses (L-FO and H-FO) improves Nrf2-activated cyto-protection (by phase 2 enzymes), while a significant increase in respiration efficiency occurs in the liver mitochondria of H-FO BALB/c mice. Eustress conditions elicited by low dose CLA (L-CLA) are associated with increased activity of phase 2 enzymes, and with higher NOX1-2, mitochondrial defences, mitochondrial uncoupling protein 2 (UCP2), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) expression, compared with controls. Steatogenic effects (lipid accumulation and alteration of lipid metabolism) elicited by high CLA (H-CLA) elicited that are associated with oxidative distress, increased mitochondrial complex I/III activity and reduced levels of phase 2 enzymes, in comparison with L-CLA-treated mice. Our results confirm the steatogenic activity of H-CLA and first demonstrate the role of NOX1 and NOX2 in the eustress conditions elicited by L-CLA. Notably, the negative association of the Nrf2/PGC-1α axis with the different CLA doses provides new insight into the mechanisms underlying the hormetic effect triggered by this Nrf2 ligand.

Retention of zirconia crowns to Ti-base abutments: effect of luting protocol, abutment treatment and autoclave sterilization.

PURPOSE: To evaluate the influence of resin cement type, surface pretreatment and autoclave sterilization on the retention of Y-TZP crowns to Ti-base abutments. METHODS: Y-TZP crowns were designed and milled to fit Ti-base abutments. Crowns were cemented using either a conventional resin cement (conventional) with a universal adhesive or a self-adhesive resin cement (self-adhesive), both following no surface pretreatment (No) or Ti-base abutment sandblasting (SB) (n=20/group). Half of the cemented samples were subjected to in-office autoclave sterilization. Pullout testing was performed in a universal testing machine at a speed of 1 mm/min until crown displacement. Data were statistically evaluated through a linear mixed model following post hoc comparisons by LSD test. RESULTS: Pullout data as a function of cement type demonstrated higher retention for conventional relative to self-adhesive cement (p < 0.001). Ti-base sandblasting (SB) favored crown retentiveness over No pretreatment (p < 0.001). Sterilized crowns exhibited higher pullout values than non-sterile (p=0.036). All the two- and three-factor interaction analyses corroborated with the superior adhesive strength of conventional compared to self-adhesive cement (all, p < 0.011), as well as, SB relative to No pretreatment (all, p < 0.024). While autoclave sterilization maximized bond strength when self-adhesive cement (data collapsed over surface pretreatment, p < 0.050) and No pretreatment were evaluated (data collapsed over surface pretreatment, p < 0.013), no significant difference was observed for conventional resin cement (p=0.280) and SB (p=0.878) groups. CONCLUSIONS: Conventional resin cement and/or Ti-base sandblasting increased Y-TZP crown retentiveness, with no significant influence of autoclave sterilization. Autoclaving increased retentiveness when self-adhesive cement and/or no Ti-base pretreatment were used.