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Sex differences in plasma metabolites in a guinea pig model of allergic asthma

. 2023 Dec 29 ; 72 (S5) : S499-S508.

Language English Country Czech Republic Media print

Document type Journal Article

Sex seems to be a contributing factor in the pathogenesis of bronchial asthma. This study aimed to find sex-related differences in metabolome measured by hydrogen-1 nuclear magnetic resonance ((1)H NMR) spectroscopy in healthy and ovalbumin (OVA)-sensitized guinea pigs. Adult male and female animals were divided into controls and OVA-sensitized groups. OVA-sensitization was performed by OVA systemic and inhalational administration within 14 days; on day 15, animals were killed by anesthetic overdose followed by exsanguination. Blood was taken and differential white blood cell count was measured. Left lung was saline-lavaged and differential cell count in the bronchoalveolar lavage fluid (BALF) was measured. After blood centrifugation, plasma was processed for (1)H NMR analysis. Metabolomic data was evaluated by principal component analysis (PCA). Eosinophil counts elevated in the BALF confirming eosinophil-mediated inflammation in OVA-sensitized animals of both sexes. Sex differences for lactate, glucose, and citrate were found in controls, where these parameters were lower in males than in females. In OVA-sensitized males higher glucose and lower pyruvate were found compared to controls. OVA-sensitized females showed lower lactate, glucose, alanine, 3-hydroxy-butyrate, creatine, pyruvate, and succinate concentrations compared to controls. In OVA-sensitized animals, lactate concentration was lower in males. Data from females (healthy and OVA-sensitized) were generally more heterogeneous. Significant sex differences in plasma concentrations of metabolites were found in both healthy and OVA-sensitized animals suggesting that sex may influence the metabolism and may thereby contribute to different clinical picture of asthma in males and females.

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Papi A, Brightling C, Pedersen SE, Reddel HK. Asthma. Lancet. 2018;391:783–800. doi: 10.1016/S0140-6736(17)33311-1. PubMed DOI

Kuruvilla ME, Lee FEH, Lee GB. Understanding Asthma Phenotypes, Endotypes, and Mechanisms of Disease. Clin Rev Allergy Immunol. 2019;56:219–233. doi: 10.1007/s12016-018-8712-1. PubMed DOI PMC

Chowdhury NU, Guntur VP, Newcomb DC, Wechsler ME. Sex and gender in asthma. Eur Respir Rev. 2021;30:210067. doi: 10.1183/16000617.0067-2021. PubMed DOI PMC

Mokra D, Barosova R, Mokry J. Sex-Based Differences in Bronchial Asthma: What Are the Mechanisms behind Them. Appl Sci. 2023;13:2694. doi: 10.3390/app13042694. DOI

Fuseini H, Newcomb DC. Mechanisms driving gender differences in asthma. Curr Allergy Asthma Rep. 2017;17:19. doi: 10.1007/s11882-017-0686-1. PubMed DOI PMC

Laffont S, Blanquart E, Guéry JC. Sex Differences in Asthma: A Key Role of Androgen-Signaling in Group 2 Innate Lymphoid Cells. Front Immunol. 2017;8:1069. doi: 10.3389/fimmu.2017.01069. PubMed DOI PMC

Villaseñor A, Eguiluz-Gracia I, Moreira A, Wheelock CE, Escribese MM. Metabolomics in the Identification of Biomarkers of Asthma. Metabolites. 2021;11:346. doi: 10.3390/metabo11060346. PubMed DOI PMC

Wang C, Jiang S, Zhang S, Ouyang Z, Wang G, Wang F. Research Progress of Metabolomics in Asthma. Metabolites. 2021;11:567. doi: 10.3390/metabo11090567. PubMed DOI PMC

Kelly RS, Sordillo JE, Lasky-Su J, Dahlin A, Perng W, Rifas-Shiman SL, Weiss ST, et al. Plasma metabolite profiles in children with current asthma. Clin Exp Allergy. 2018;48:1297–1304. doi: 10.1111/cea.13183. PubMed DOI PMC

Xu S, Panettieri RA, Jude J. Metabolomics in asthma: A platform for discovery. Mol Aspects Med. 2022;85:100990. doi: 10.1016/j.mam.2021.100990. PubMed DOI PMC

Saude EJ, Skappak CD, Regush S, Cook K, Ben-Zvi A, Becker A, Moqbel R, et al. Metabolomic profiling of asthma: Diagnostic utility of urine nuclear magnetic resonance spectroscopy. J Allergy Clin Immunol. 2011;127:757–764.e1-6. doi: 10.1016/j.jaci.2010.12.1077. PubMed DOI

Saude EJ, Obiefuna IP, Somorjai RL, Ajamian F, Skappak C, Ahmad T, Dolenko BK, et al. Metabolomic Biomarkers in a Model of Asthma Exacerbation. Am J Respir Crit Care Med. 2009;179:25–34. doi: 10.1164/rccm.200711-1716OC. PubMed DOI

Quinn KD, Schedel M, Nkrumah-Elie Y, Joetham A, Armstrong M, Cruickshank-Quinn C, Reisdorph R, Gelfand EW, Reisdorph N. Dysregulation of metabolic pathways in a mouse model of allergic asthma. Allergy. 2017;72:1327–1337. doi: 10.1111/all.13144. PubMed DOI

Ho WE, Xu YJ, Xu F, Cheng C, Peh HY, Tannenbaum SR, Wong WS, Ong CN. Metabolomics Reveals Altered Metabolic Pathways in Experimental Asthma. Am J Respir Cell Mol Biol. 2013;48:204–211. doi: 10.1165/rcmb.2012-0246OC. PubMed DOI PMC

Kertys M, Grendar M, Kosutova P, Mokra D, Mokry J. Plasma based targeted metabolomic analysis reveals alterations of phosphatidylcholines and oxidative stress markers in guinea pig model of allergic asthma. Biochim Biophys Acta Mol Basis Dis. 2020;1866:165572. doi: 10.1016/j.bbadis.2019.165572. PubMed DOI

Costanzo M, Caterino M, Sotgiu G, Ruoppolo M, Franconi F, Campesi I. Sex differences in the human metabolome. Biol Sex Differ. 2022;13:30. doi: 10.1186/s13293-022-00440-4. PubMed DOI PMC

Krumsiek J, Mittelstrass K, Do KT, Stückler F, Ried J, Adamski J, Peters A, et al. Gender-specific pathway differences in the human serum metabolome. Metabolomics. 2015;11:1815–1833. doi: 10.1007/s11306-015-0829-0. PubMed DOI PMC

Liu J, Zhu J, Jiang H, Zhang S, Tang S, Yang R, Gong X, Zhang L. Dual-Directional Regulation of Belamcanda chinensis Extract on Ovalbumin-Induced Asthma in Guinea Pigs of Different Sexes Based on Serum Metabolomics. Evid Based Complement Alternat Med. 2022;2022:5266350. doi: 10.1155/2022/5266350. PubMed DOI PMC

Mokry J, Urbanova A, Medvedova I, Kertys M, Mikolka P, Kosutova P, Mokra D. Effects of tadalafil (PDE5 inhibitor) and roflumilast (PDE4 inhibitor) on airway reactivity and markers of inflammation in ovalbumin-induced airway hyperresponsiveness in guinea pigs. J Physiol Pharmacol. 2017;68:721–730. PubMed

Nagana Gowda GA, Gowda YN, Raftery D. Expanding the limits of human blood metabolite quantitation using NMR spectroscopy. Anal Chem. 2015;87:706–715. doi: 10.1021/ac503651e. PubMed DOI PMC

Wishart DS, Guo A, Oler E, Wang F, Anjum A, Peters H, Dizon R, et al. HMDB 5.0: the Human Metabolome Database for 2022. Nucleic Acids Res. 2022;50:D622–D631. doi: 10.1093/nar/gkab1062. PubMed DOI PMC

Pang Z, Chong J, Zhou G, de Lima Morais DA, Chang L, Barrette M, Gauthier C, et al. MetaboAnalyst 5.0: narrowing the gap between raw spectra and functional insights. Nucleic Acids Res. 2021;49:W388–W396. doi: 10.1093/nar/gkab382. PubMed DOI PMC

Ricciardolo FLM, Nijkamp F, De Rose V, Folkerts G. The guinea pig as an animal model for asthma. Curr Drug Targets. 2008;9:452–465. doi: 10.2174/138945008784533534. PubMed DOI

Thakur VR, Khuman V, Beladiya JV, Chaudagar KK, Mehta AA. An experimental model of asthma in rats using ovalbumin and lipopolysaccharide allergens. Heliyon. 2019;5:e02864. doi: 10.1016/j.heliyon.2019.e02864. PubMed DOI PMC

Devries MC, Hamadeh MJ, Phillips SM, Tarnopolsky MA. Menstrual cycle phase and sex influence muscle glycogen utilization and glucose turnover during moderate-intensity endurance exercise. Am J Physiol Regul Integr Comp Physiol. 2006;291:R1120–R1128. doi: 10.1152/ajpregu.00700.2005. PubMed DOI

Ruby BC, Coggan AR, Zderic TW. Gender differences in glucose kinetics and substrate oxidation during exercise near the lactate threshold. J Appl Physiol. 2002;92:1125–1132. doi: 10.1152/japplphysiol.00296.2001. PubMed DOI

Pietrobelli A, Allison DB, Heshka S, Heo M, Wang ZM, Bertkau A, Laferrère B, Rosenbaum M, Aloia JF, Pi-Sunyer FX, Heymsfield SB. Sexual dimorphism in the energy content of weight change. Int J Obes. 2002;26:1339–1348. doi: 10.1038/sj.ijo.0802065. PubMed DOI

Bell JA, Santos Ferreira DL, Fraser A, Soares ALG, Howe LD, Lawlor DA, Carslake D, Davey Smith G, O’Keeffe LM. Sex differences in systemic metabolites at four life stages: cohort study with repeated metabolomics. BMC Med. 2021;19:58. doi: 10.1186/s12916-021-01929-2. PubMed DOI PMC

Hagobian TA, Sharoff CG, Stephens BR, Wade GN, Silva JE, Chipkin SR, Braun B. Effects of exercise on energy-regulating hormones and appetite in men and women. Am J Physiol Regul Integr Comp Physiol. 2009;296:R233–R242. doi: 10.1152/ajpregu.90671.2008. PubMed DOI PMC

Brooks GA, Arevalo JA, Osmond AD, Leija RG, Curl CC, Tovar AP. Lactate in contemporary biology: a phoenix risen. J Physiol. 2022;600:1229–1251. doi: 10.1113/JP280955. PubMed DOI PMC

Gustavsson C, Yassin K, Wahlström E, Cheung L, Lindberg J, Brismar K, Ostenson CG, Norstedt G, Tollet-Egnell P. Sex-different hepatic glycogen content and glucose output in rats. BMC Biochem. 2010;11:38. doi: 10.1186/1471-2091-11-38. PubMed DOI PMC

Roshan Lal T, Cechinel LR, Freishtat R, Rastogi D. Metabolic Contributions to Pathobiology of Asthma. Metabolites. 2023;13:212. doi: 10.3390/metabo13020212. PubMed DOI PMC

Li X, Yang Y, Zhang B, Lin X, Fu X, An Y, Zou Y, Wang J-X, Wang Z, Yu T. Lactate metabolism in human health and disease. Sig Transduct Target Ther. 2022;7:1–22. doi: 10.1038/s41392-019-0089-y. PubMed DOI PMC

Kadowaki M, Yamada H, Sato K, Shigemi H, Umeda Y, Morikawa M, Waseda Y, et al. Extracellular acidification-induced CXCL8 production through a proton-sensing receptor OGR1 in human airway smooth muscle cells: a response inhibited by dexamethasone. J Inflamm (Lond) 2019;16:4. doi: 10.1186/s12950-019-0207-1. PubMed DOI PMC

Meert KL, McCaulley L, Sarnaik AP. Mechanism of lactic acidosis in children with acute severe asthma. Pediatr Crit Care Med. 2012;13:28–31. doi: 10.1097/PCC.0b013e3182196aa2. PubMed DOI

Rodrigo GJ. Serum Lactate Increase During Acute Asthma Treatment: A New Piece of the Puzzle. Chest. 2014;145:6–7. doi: 10.1378/chest.13-2042. PubMed DOI

Jung J, Kim SH, Lee HS, Choi GS, Jung YS, Ryu DH, Park HS, Hwang GS. Serum metabolomics reveals pathways and biomarkers associated with asthma pathogenesis. Clin Exp Allergy. 2013;43:425–433. doi: 10.1111/cea.12089. PubMed DOI

Koskela HO, Salonen PH, Niskanen L. Hyperglycaemia during exacerbations of asthma and chronic obstructive pulmonary disease. Clin Respir J. 2013;7:382–389. doi: 10.1111/crj.12020. PubMed DOI

Rastogi D, Fraser S, Oh J, Huber AM, Schulman Y, Bhagtani RH, Khan ZS, et al. Inflammation, metabolic dysregulation, and pulmonary function among obese urban adolescents with asthma. Am J Respir Crit Care Med. 2015;191:149–160. doi: 10.1164/rccm.201409-1587OC. PubMed DOI PMC

Qu HQ, Glessner J, Qu J, Gilhool S, Mentch F, Campbell I, Sleiman P, et al. Metabolomic profiling of samples from pediatric patients with asthma unveils deficient nutrients in African Americans. iScience. 2022;25:104650. doi: 10.1016/j.isci.2022.104650. PubMed DOI PMC

Comhair SAA, McDunn J, Bennett C, Fettig J, Erzurum SC, Kalhan SC. Metabolomic Endotype of Asthma. J Immunol. 2015;195:643–650. doi: 10.4049/jimmunol.1500736. PubMed DOI PMC

Mierziak J, Burgberger M, Wojtasik W. 3-Hydroxybutyrate as a Metabolite and a Signal Molecule Regulating Processes of Living Organisms. Biomolecules. 2021;11:402. doi: 10.3390/biom11030402. PubMed DOI PMC

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