Peroxisome proliferator activated receptor‐gamma stimulation for prevention of 5‐fluorouracil‐induced oral mucositis in mice

Abstract

The RGZ had a protective effect on oral mucosa damaged by chemotherapy. These data encourage the further study of RGZ for the prevention of 5-FU-induced mucositis in patients with cancer.

β-Caryophyllene Reduces the Inflammatory Phenotype of Periodontal Cells by Targeting CB2 Receptors

“…PPARγ is a nuclear receptor that may be considered as an "atypical transcription factor" able to activate anti-inflammatory signals. Indeed, pharmacological stimulation of PPARγ exerts beneficial activity in oral mucositis [13,14]. In agreement with these findings we also investigated PPARγ and its co-activator PGC-1α and we found that the expression of this intracellular signal was "downregulated" in our model of oral mucositis.…”

“…In fact, ROS boosts the translocation to the nucleus of Nuclear Factor Kappa B (NF-κB) [12]. Once it reaches the nucleus, the transcription factor turns on genes that codify for inflammatory cytokines such as Tumor Necrosis Factor (TNF-α), Interleukin 1 beta (IL-1β) and IL-6; moreover at the same time, it silences genes priming anti-inflammatory signals, in particular IL-13 and the nuclear receptor called peroxisome proliferator-activated receptor gamma (PPAR-γ) [13,14]. Indeed, this NF-κB primed cytokine storm may be considered an important arm of the acute phase response, but it has also been reported to have a key role in driving the second wave of the acute response in mammals.…”

Emerging approaches of wound healing in experimental models of high-grade oral mucositis induced by anticancer therapy

“…RGZ is an intracellular ligand for PPAR-γ transcription factor that exerts antioxidant and anti-inflammatory activities. Currently, RGZ is used to control hyperglycemia in type II diabetes mellitus [ 55 , 56 ]. Additionally, it has been reported that the thiazolidinedione family of PPARγ agonists, including troglitazone (TGZ), pioglitazone (PGZ) and RGZ, have antitumor effects [ 57 , 58 ].…”

“…One of the ways that PPARs regulate inflammation is through a transrepression mechanism, where other transcription-factor, such as NF-κβ, is repressed to activate the expression of pro-inflammatory cytokines [ 55 ]. Consistent with the RGZ effects, Sottili and collaborators (2017) tested RGZ in a 5-FU-induced OM in mouse models.…”

“…Consistent with the RGZ effects, Sottili and collaborators (2017) tested RGZ in a 5-FU-induced OM in mouse models. RGZ was administered at 5 mg/kg/day by oral gavage, starting 24 hours before the 5-FU induction for 15 days [ 55 ]. The authors demonstrated that RGZ inhibited the activation of NF-κβ protein leading to a reduced expression of TGF-β and IL-1β cytokines in the site of lesions.…”