PMID- 36468814 OWN - NLM STAT- MEDLINE DCOM- 20230320 LR - 20230320 IS - 1099-0461 (Electronic) IS - 1095-6670 (Linking) VI - 37 IP - 3 DP - 2023 Mar TI - Fingolimod attenuates ovalbumin-induced airway inflammation via inhibiting MAPK/ERK signaling in mice. PG - e23266 LID - 10.1002/jbt.23266 [doi] AB - The current study was designed to investigate the potential anti-inflammatory and antioxidant effects of fingolimod against Ovalbumin (Ova)-induced allergic airway inflammation compared to dexamethasone. Fingolimod was given (0.5 mg/kg/day, p.o.) for sensitized mice 1 h before Ova challenge from Days 19 to 24. Fingolimod significantly inhibited Ova-induced elevation of inflammatory cells and eosinophils numbers in bronchoalveolar lavage fluid (BALF) and reduced concentrations of immunoglobulin E in serum and of sphingosine-1-phosphate, interleukin (IL)-4, and IL-13 in BALF. Fingolimod inhibited microvascular leakage and edema as reflected by the decreased lung/body weight index. These findings were supported by histopathological examination results showing that fingolimod substantially decreased perivascular edema and inflammatory cell infiltration. Fingolimod also attenuated Ova-induced oxidative stress as evidenced by decreased malondialdehyde concentration along with increasing concentrations of reduced glutathione and superoxide dismutase in lung tissues. Fingolimod also significantly decreased monocyte chemoattractant protein-1 (MCP-1), p-ERK, and p-P38 in lung tissues of Ova-challenged mice. In conclusion, the current study demonstrated the anti-inflammatory and antioxidant effects of fingolimod in allergic airway inflammation that might be associated with the downregulation of mitogen activated kinases signaling to decrease T helper 2 cytokine secretion (IL-4 and IL-13) and MCP-1 expression, along with the inhibition of oxidative stress. CI - (c) 2022 Wiley Periodicals LLC. FAU - Makled, Mirhan N AU - Makled MN AUID- ORCID: 0000-0002-2981-6324 AD - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt. FAU - El-Sheakh, Ahmed R AU - El-Sheakh AR AUID- ORCID: 0000-0003-2745-3811 AD - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt. AD - Future Studies and Risks Management & National Committee of Drugs, Academy of Scientific Research, Ministry of Higher Education, ElSayeda Zeinab, Egypt. LA - eng PT - Journal Article DEP - 20221205 PL - United States TA - J Biochem Mol Toxicol JT - Journal of biochemical and molecular toxicology JID - 9717231 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Antioxidants) RN - 0 (Cytokines) RN - G926EC510T (Fingolimod Hydrochloride) RN - 0 (Interleukin-13) RN - 9006-59-1 (Ovalbumin) SB - IM MH - Animals MH - Mice MH - Anti-Inflammatory Agents/pharmacology MH - Antioxidants/metabolism MH - *Asthma MH - Bronchoalveolar Lavage Fluid MH - Cytokines/metabolism MH - Disease Models, Animal MH - Fingolimod Hydrochloride MH - Inflammation/metabolism MH - Interleukin-13 MH - Lung/metabolism MH - Mice, Inbred BALB C MH - Ovalbumin MH - MAP Kinase Signaling System OTO - NOTNLM OT - allergic airway inflammation OT - fingolimod OT - interleukins OT - p-ERK OT - p38 MAPK EDAT- 2022/12/06 06:00 MHDA- 2023/03/15 06:00 CRDT- 2022/12/05 08:42 PHST- 2022/10/06 00:00 [revised] PHST- 2022/04/12 00:00 [received] PHST- 2022/11/15 00:00 [accepted] PHST- 2022/12/06 06:00 [pubmed] PHST- 2023/03/15 06:00 [medline] PHST- 2022/12/05 08:42 [entrez] AID - 10.1002/jbt.23266 [doi] PST - ppublish SO - J Biochem Mol Toxicol. 2023 Mar;37(3):e23266. doi: 10.1002/jbt.23266. Epub 2022 Dec 5.