PMID- 36314140 OWN - NLM STAT- MEDLINE DCOM- 20230116 LR - 20230116 IS - 1365-2591 (Electronic) IS - 0143-2885 (Linking) VI - 56 IP - 2 DP - 2023 Feb TI - Selenium ameliorates inflammation by decreasing autophagic flux and mitogen-activated protein kinase signalling on experimentally induced rat periapical lesions. PG - 227-244 LID - 10.1111/iej.13861 [doi] AB - AIM: To reveal the molecular mechanisms that targets mitogen-activated protein kinase (MAPK) signalling and the autophagic flux and to investigate the possible effects of the systemic administration of selenium (Se) on experimentally induced rat periapical lesions. METHODOLOGY: Thirty adult Sprague-Dawley rats were divided equally into negative control, positive control and Se groups. In the positive control and Se groups, the pulp chambers of their mandibular first molars were exposed to the oral environment to induce periapical lesions The Se group received daily intraperitoneal injections of Se at a dose of 0.1 mg kg(-1) . After 28 days, the amount of bone destruction; severity of inflammation; penetration of microorganisms along the root canal; collagen degradation in periodontal ligament; interleukin (IL)-6, hypoxia-inducible factor-1 (HIF-1), cyclooxygenase-2 (COX-2) and caspase-3 expression; autophagic flux; and p38 MAPK signalling were evaluated using radiographic, histopathological, Gram staining, picrosirius red stain, immunohistochemical, quantitative real-time polymerase chain (qRT-PCR) and Western blot methods, respectively. These data were analysed through the Kruskal-Wallis and Dunnett's tests (p < .05). RESULTS: The area of radiographic periapical bone loss, histopathological scores, the area of periapical bone loss and the scores for the bacteria localisation, the intensity of immunohistochemical staining for IL-6, HIF-1, COX-2 and caspase-3 in the Se group was significantly less than those of the positive control group (p < .01). The mRNA expression levels of Beclin-1, Atg3, Atg5, Atg7 and Atg16L1 were lower in the Se group than in the positive control group (p < .01). The protein expressions of Beclin-1, Atg5 and LC3-II, the phosphorylation ratio of the p38 MAPK and the ratios of LC3II/LC3I were significantly higher (p < .05) in the positive control and Se groups. On the contrary, the expression of the p62/SQSTM1 protein was significantly lower (p < .05) in the positive control and Se groups than in the negative control group. CONCLUSION: The induction of periapical lesions in rats increased autophagic flux and activated p38 MAPK signal transduction processes. Se suppressed the inflammatory process, reduced bone destruction and both the autophagic flux and p38 MAPK activation. CI - (c) 2022 British Endodontic Society. Published by John Wiley & Sons Ltd. FAU - Bolat, Nergiz AU - Bolat N AD - Department of Endodontics, Faculty of Dentistry, Suleyman Demirel University, Isparta, Turkey. FAU - Erzurumlu, Yalcin AU - Erzurumlu Y AD - Department of Biochemistry, Faculty of Pharmacy, Suleyman Demirel University, Isparta, Turkey. FAU - Asci, Halil AU - Asci H AD - Department of Pharmacology, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey. FAU - Ozmen, Ozlem AU - Ozmen O AD - Department of Pathology, Faculty of Veterinary, Mehmet Akif Ersoy University, Burdur, Turkey. FAU - Ureyen Kaya, Bulem AU - Ureyen Kaya B AUID- ORCID: 0000-0002-8295-4347 AD - Department of Endodontics, Faculty of Dentistry, Suleyman Demirel University, Isparta, Turkey. LA - eng GR - TDH-2020-8040/Department of Scientific Research Projects, Suleyman Demirel University/ PT - Journal Article DEP - 20221109 PL - England TA - Int Endod J JT - International endodontic journal JID - 8004996 RN - H6241UJ22B (Selenium) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 3.4.22.- (Caspase 3) RN - 0 (Beclin-1) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) MH - Rats MH - Animals MH - Rats, Sprague-Dawley MH - *Selenium MH - Mitogen-Activated Protein Kinases/metabolism MH - Caspase 3/metabolism MH - Beclin-1 MH - Cyclooxygenase 2/metabolism MH - Inflammation MH - Signal Transduction MH - p38 Mitogen-Activated Protein Kinases/metabolism OTO - NOTNLM OT - MAPK OT - animal model OT - autophagy OT - inflammation OT - periapical lesion OT - selenium EDAT- 2022/11/01 06:00 MHDA- 2023/01/17 06:00 CRDT- 2022/10/31 05:18 PHST- 2022/10/24 00:00 [revised] PHST- 2022/03/14 00:00 [received] PHST- 2022/10/25 00:00 [accepted] PHST- 2022/11/01 06:00 [pubmed] PHST- 2023/01/17 06:00 [medline] PHST- 2022/10/31 05:18 [entrez] AID - 10.1111/iej.13861 [doi] PST - ppublish SO - Int Endod J. 2023 Feb;56(2):227-244. doi: 10.1111/iej.13861. Epub 2022 Nov 9.