Original Contribution
Mass spectrometry-based metabolomic profiling identifies alterations in salivary redox status and fatty acid metabolism in response to inflammation and oxidative stress in periodontal disease

https://doi.org/10.1016/j.freeradbiomed.2014.02.024Get rights and content

Highlights

  • Ionomics identified decreased salivary levels of Mn, Cu, and Zn in periodontal patients.

  • Levels of SODs were decreased in saliva and serum in the periodontal group.

  • Elevated levels of COX products in periodontal saliva indicate enhanced inflammatory response.

  • The oxidative stress marker F2-isoprostane was significantly increased in periodontal saliva.

  • Our study highlights a linkage of redox status, oxidative stress, and inflammation in periodontitis.

Abstract

Periodontal diseases represent the most common chronic inflammatory diseases in humans and a major cause of tooth loss. Combining mass spectrometry-based ionomics and targeted lipidomics on fatty acid metabolites, we identified significant alterations in redox status and fatty acid metabolism in saliva in response to chronic inflammation and oxidative stress in periodontal disease in a cohort of nonsmoker subjects with chronic periodontitis. For the first time, ionomic profiling of around 30 ions in saliva revealed significantly decreased levels of redox-active metal ions including Mn, Cu, and Zn in the periodontal group, which is consistent with decreased levels of superoxide dismutases in saliva and serum. A targeted lipidomic approach was employed to monitor the major metabolites of arachidonic acid and linoleic acid in saliva. We observed increased levels of cyclooxygenase products including PGE2, PGD2, and PGF and TXB2, but decreased level of PGI2 in the periodontal group. A unique pattern of the lipoxygenase products of arachidonic acid and linoleic acid was observed with increased level of 5-HETE but decreased levels of 13-HODE and 9-HODE. Levels of salivary F2-isoprostanes, free radical lipid peroxidation products, and a gold standard for oxidative stress in vivo were also significantly elevated. Taking these data together, our study using multiple powerful omics techniques demonstrates that local redox alteration contributes significantly to periodontitis through the modulation of fatty acid metabolism in response to inflammation and oxidative stress. This study highlights the importance of redox status in periodontitis and provides a rationale for preventing periodontal disease by dietary interventions aiming to restore redox balance.

Section snippets

Reagents

SOD, xanthine oxidase, luminol, xanthine, and vitamins A, E, and C were purchased from Sigma–Aldrich Chemical (Milwaukee, WI, USA). HPLC-quality solvents, such as methanol, water, 2-propanol, hexane, and acetonitrile, were purchased from either Fisher Chemical (Phillipsburg, NJ, USA) or EM Science (Gibbstown, NJ, USA). Standards and deuterated standards of arachidonic acid including PGD2, E2, F, I2; TXB2; 5-HETE, 12-HETEs, 15-HETEs; HODEs; and EETs were purchased from Cayman Chemicals (Ann

ICP–MS-based ionomic profiling in saliva revealed significant alterations in redox status in saliva from periodontal patients

Compelling evidence suggests that periodontitis results from chronic inflammation and oxidative stress conditions caused by a loss of the delicate balance between host antioxidant defense and pro-oxidative factors. Furthermore, nutritional factors including antioxidant vitamins (vitamins C, A, and E) and minerals seem to play an important role in maintaining the balance of systematic redox status. We conducted an FFQ and 72-h diet recall to investigate the dietary patterns and antioxidant

Discussion

Periodontal diseases including gingivitis and periodontitis are the most prevalent inflammatory conditions in humans. Research conducted during the past decade has demonstrated that individual risk for periodontitis includes microbiological, genetic, and environmental factors, among which dietary habit plays an important role. Furthermore, it remains poorly understood how inflammatory response and alterations in local and systemic redox status under oxidative stress contribute to progression of

Acknowledgments

M.Z. acknowledges financial support of an A29 grant from the Shanghai Municipal Mission of Health and Family Planning (20114103). H.Y. acknowledges financial support of grants from the Ministry of Science and Technology of China (2012BAK01B00), National Key Basic Research Program of China (973 Program, No. 2012CB524900), National Natural Science Foundation of China (31170809), and Hundred Talents Program from the Chinese Academy of Sciences (2012OHTP07). We acknowledge the help in the SOD

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