PMID- 31422500 OWN - NLM STAT- MEDLINE DCOM- 20200601 LR - 20200601 IS - 1573-3890 (Electronic) IS - 1573-3882 (Linking) VI - 15 IP - 8 DP - 2019 Aug 17 TI - Metabolomic study on bleomycin and polyhexamethylene guanidine phosphate-induced pulmonary fibrosis mice models. PG - 111 LID - 10.1007/s11306-019-1574-6 [doi] AB - INTRODUCTION: Polyhexamethylene guanidine phosphate (PHMG) has been used as a disinfectant and biocide, and was known to be harmless and non-toxic. However, in 2011, PHMG used as a humidifier disinfectant was reported to be associated with lung diseases, such as, fibrosis in the toxicant studies on pulmonary fibrosis by PHMG. However, no metabolomics study has been performed in PHMG-induced mouse models of pulmonary fibrosis. OBJECTIVES: We performed a metabolomic study to understand the biochemical events that occur in bleomycin (BLM)- and PHMG-induced mouse models of pulmonary fibrosis using gas chromatography-mass spectrometry (GC-MS), LC-tandem MS, and GC-tandem MS. RESULTS: The levels of 61 metabolites of 30 amino acids, 13 organic acids, 12 fatty acids, 5 polyamines, and oxidized glutathione were determined in the pulmonary tissues of mice with BLM- and PHMG-induced pulmonary fibrosis and in normal controls. Principal component analysis and partial least squares discriminant analysis used to compare level of these 61 metabolites in pulmonary tissues. Levels of metabolites were significantly different in the BLM and PHMG groups as compared with the control group. In particular, the BLM- and PHMG-induced pulmonary fibrosis models showed elevated collagen synthesis and oxidative stress and metabolic disturbance of TCA related organic acids including fumaric acid by NADPH oxidase. In addition, polyamine metabolism showed severe alteration in the PHMG group than that of the BLM group. CONCLUSION: This result suggests PHMG will be able to induce pulmonary fibrosis by arginine metabolism and NADPH oxidase signaling. FAU - Seo, Chan AU - Seo C AD - College of Pharmacy, Sunchon National University, Suncheon, 540-950, Republic of Korea. FAU - Kim, Sung-Hwan AU - Kim SH AD - National Center for Efficacy Evaluation of Respiratory Disease Product, Institute of Toxicology, Jeongeup-si, 56212, Republic of Korea. FAU - Lee, Hyeon-Seong AU - Lee HS AD - College of Pharmacy, Sunchon National University, Suncheon, 540-950, Republic of Korea. FAU - Ji, Moongi AU - Ji M AD - College of Pharmacy, Sunchon National University, Suncheon, 540-950, Republic of Korea. FAU - Min, Jeuk AU - Min J AD - College of Pharmacy, Sunchon National University, Suncheon, 540-950, Republic of Korea. FAU - Son, Young-Jin AU - Son YJ AD - College of Pharmacy, Sunchon National University, Suncheon, 540-950, Republic of Korea. FAU - Kim, In-Hyeon AU - Kim IH AD - National Center for Efficacy Evaluation of Respiratory Disease Product, Institute of Toxicology, Jeongeup-si, 56212, Republic of Korea. FAU - Lee, Kyuhong AU - Lee K AD - National Center for Efficacy Evaluation of Respiratory Disease Product, Institute of Toxicology, Jeongeup-si, 56212, Republic of Korea. khleekit@gmail.com. FAU - Paik, Man-Jeong AU - Paik MJ AUID- ORCID: 0000-0003-1654-3133 AD - College of Pharmacy, Sunchon National University, Suncheon, 540-950, Republic of Korea. paik815@sunchon.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190817 PL - United States TA - Metabolomics JT - Metabolomics : Official journal of the Metabolomic Society JID - 101274889 RN - 0 (Guanidines) RN - 11056-06-7 (Bleomycin) RN - 31961-54-3 (polyhexamethyleneguanidine) SB - IM MH - Animals MH - Bleomycin/administration & dosage/analysis/*metabolism MH - Chromatography, Gas MH - Chromatography, Liquid MH - *Disease Models, Animal MH - Guanidines/administration & dosage/analysis/*metabolism MH - Male MH - *Metabolomics MH - Mice MH - Mice, Inbred C57BL MH - Pulmonary Fibrosis/*chemically induced/*metabolism/pathology MH - Tandem Mass Spectrometry OTO - NOTNLM OT - Bleomycin OT - Metabolic profiling analysis OT - Metabolomics OT - Polyhexamethylene guanidine phosphate OT - Pulmonary fibrosis OT - Tandem mass spectrometry EDAT- 2019/08/20 06:00 MHDA- 2020/06/02 06:00 CRDT- 2019/08/19 06:00 PHST- 2019/01/22 00:00 [received] PHST- 2019/08/01 00:00 [accepted] PHST- 2019/08/19 06:00 [entrez] PHST- 2019/08/20 06:00 [pubmed] PHST- 2020/06/02 06:00 [medline] AID - 10.1007/s11306-019-1574-6 [pii] AID - 10.1007/s11306-019-1574-6 [doi] PST - epublish SO - Metabolomics. 2019 Aug 17;15(8):111. doi: 10.1007/s11306-019-1574-6.