Non-Targeted Metabolomics Signature in the Plasma and Bone Marrow of Patients with Long Bone Injuries

Author(s): Hend Ibrahim, Omar Alnachoukati, Bridget A. Baxter, Trinette Chapin, Thomas Schroeppel, Julie Dunn, Elizabeth P. Ryan*

Journal Name: Current Metabolomics and Systems Biology
Formerly Current Metabolomics

Volume 7 , Issue 1 , 2020

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

Background: The contribution of long bone injury and reaming to the inflammatory response of trauma is unknown.

Introduction: This study evaluated whether metabolomics can be used to (1) reveal differences in the plasma from long bone injury trauma patients before and after reaming and (2) distinguish healthy adult plasma from that of trauma patients.

Methods: Prospective cohort study with enrollment from February 17, 2017 to December 5, 2017 included 15 patients with long bone injuries and 20 healthy adults. Patients with femoral or tibial fractures scheduled to undergo intramedullary nailing were identified at the Medical Center of the Rockies, (Loveland, Co), and Memorial Hospital, (Colorado Springs, CO). Pre-and post-reaming plasma and bone marrow from fifteen patients with femoral and tibial fractures and 20 heathy adult plasma were analyzed by ultra-high-performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS).

Results: Trauma patients had 1259 plasma metabolites and healthy adults had 1272 plasma metabolites detected. Fifty percent (657 metabolites) were common between the bone marrow and plasma profiles, and 304 metabolites showed statistical significance for differential abundance between pre- and post-reaming (P<0.05). Post-ream lipids, fatty acids and ceramides were 1.09-1.46-fold increased and diacylglycerols were 0.73-0.82-fold decreased compared to the pre-ream patient control. Post-ream tryptophan metabolites were decreased 0.84-fold, whereas cysteine metabolites were elevated 1.42-fold. Metabolite signals associated with bone matrix remodeling, stress and inflammation were modulated in all patients.

Conclusion: Plasma metabolite signatures changed in long bone fracture patients pre- and post-reaming showing distinct profiles from healthy adults without trauma injury. Metabolite signatures of long bone trauma patients have an inflammatory response reflective of healing cascades and merits additional testing for markers of individualized responses to injury.

Keywords: Bone marrow, plasma, metabolomics, fracture, reaming, trauma, inflammation.

[1]
Pape, H.C.; Grimme, K.; Van Griensven, M.; Sott, A.H.; Giannoudis, P.; Morley, J.; Roise, O.; Ellingsen, E.; Hildebrand, F.; Wiese, B.; Krettek, C. EPOFF Study Group. Impact of intramedullary instrumentation versus damage control for femoral fractures on immunoinflammatory parameters: prospective randomized analysis by the EPOFF Study Group. J. Trauma, 2003, 55(1), 7-13.
[http://dx.doi.org/10.1097/01.TA.0000075787.69695.4E] [PMID: 12855874]
[2]
Pell, A.C.; Christie, J.; Keating, J.F.; Sutherland, G.R. The detection of fat embolism by transoesophageal echocardiography during reamed intramedullary nailing. A study of 24 patients with femoral and tibial fractures. J. Bone Joint Surg. Br., 1993, 75(6), 921-925.
[http://dx.doi.org/10.1302/0301-620X.75B6.8245083] [PMID: 8245083]
[3]
Giannoudis, P.V.; van Griensven, M.; Hildebrand, F.; Krettek, C.; Pape, H.C. Femoral nailing-related coagulopathy determined by first-hit magnitude: an animal study. Clin. Orthop. Relat. Res., 2008, 466(2), 473-480.
[http://dx.doi.org/10.1007/s11999-007-0066-6] [PMID: 18196434]
[4]
Smith, R.M.; Giannoudis, P.V.; Bellamy, M.C.; Perry, S.L.; Dickson, R.A.; Guillou, P.J. Interleukin-10 release and monocyte human leukocyte antigen-DR expression during femoral nailing. Clin. Orthop. Relat. Res., 2000, (373), 233-240.
[http://dx.doi.org/10.1097/00003086-200004000-00028] [PMID: 10810482]
[5]
Hazeldine, J.; Naumann, D.N.; Toman, E.; Davies, D.; Bishop, J.R.B.; Su, Z.; Hampson, P.; Dinsdale, R.J.; Crombie, N.; Duggal, N.A.; Harrison, P.; Belli, A.; Lord, J.M. Prehospital immune responses and development of multiple organ dysfunction syndrome following traumatic injury: A prospective cohort study. PLoS Med., 2017, 14(7)e1002338
[http://dx.doi.org/10.1371/journal.pmed.1002338] [PMID: 28719602]
[6]
Peltier, L.F. Fat embolism. III. The toxic properties of neutral fat and free fatty acids. Surgery, 1956, 40(4), 665-670.
[PMID: 13371426]
[7]
Christie, J. The coagulative effects of fat embolization during intramedullary manipulative procedures. Tech. Orthop., 1996, 11(1), 14-17.
[http://dx.doi.org/10.1097/00013611-199601110-00003]
[8]
Pape, H.C.; Bartels, M.; Pohlemann, T.; Werner, T.; von Glinski, S.; Baur, H.; Tscherne, H. Coagulatory response after femoral instrumentation after severe trauma in sheep. J. Trauma, 1998, 45(4), 720-728.
[http://dx.doi.org/10.1097/00005373-199810000-00017] [PMID: 9783611]
[9]
Jaicks, R.R.; Cohn, S.M.; Moller, B.A. Early fracture fixation may be deleterious after head injury. J. Trauma, 1997, 42(1), 1-5.
[http://dx.doi.org/10.1097/00005373-199701000-00001] [PMID: 9003250]
[10]
Richards, J.E.; Guillamondegui, O.D.; Archer, K.R.; Jackson, J.C.; Ely, E.W.; Obremskey, W.T. The association of reamed intramedullary nailing and long-term cognitive impairment. J. Orthop. Trauma, 2011, 25(12), 707-713.
[http://dx.doi.org/10.1097/BOT.0b013e318225f358] [PMID: 22089759]
[11]
Hannoush, E.J.; Sifri, Z.C.; Elhassan, I.O.; Mohr, A.M.; Alzate, W.D.; Offin, M.; Livingston, D.H. Impact of enhanced mobilization of bone marrow derived cells to site of injury. J. Trauma, 2011, 71(2), 283-289.
[http://dx.doi.org/10.1097/TA.0b013e318222f380] [PMID: 21825928]
[12]
Orlic, D.; Kajstura, J.; Chimenti, S.; Bodine, D.M.; Leri, A.; Anversa, P. Bone marrow stem cells regenerate infarcted myocardium. Pediatr. Transplant., 2003, 7(Suppl. 3), 86-88.
[http://dx.doi.org/10.1034/j.1399-3046.7.s3.13.x] [PMID: 12603699]
[13]
Wozasek, G.E.; Thurnher, M.; Redl, H.; Schlag, G. Pulmonary reaction during intramedullary fracture management in traumatic shock: an experimental study. J. Trauma, 1994, 37(2), 249-254.
[http://dx.doi.org/10.1097/00005373-199408000-00017] [PMID: 8064925]
[14]
Jacobs, R.R. Fat embolism syndrome: A comparison of hematologic coagulation and lipid changes in two animal models. Clin. Orthop. Relat. Res., 1976, (116), 240-247.
[http://dx.doi.org/10.1097/00003086-197605000-00040] [PMID: 1277647]
[15]
Geilen, C.C.; Wieder, T.; Orfanos, C.E. Ceramide signalling: regulatory role in cell proliferation, differentiation and apoptosis in human epidermis. Arch. Dermatol. Res., 1997, 289(10), 559-566.
[http://dx.doi.org/10.1007/s004030050240] [PMID: 9373714]
[16]
Abboud, A.; Namas, R.A.; Ramadan, M.; Mi, Q.; Almahmoud, K.; Abdul-Malak, O.; Azhar, N.; Zaaqoq, A.; Namas, R.; Barclay, D.A.; Yin, J.; Sperry, J.; Peitzman, A.; Zamora, R.; Simmons, R.L.; Billiar, T.R.; Vodovotz, Y. Computational analysis supports an early, type 17 cell-associated divergence of blunt trauma survival and mortality. Crit. Care Med., 2016, 44(11), e1074-e1081.
[http://dx.doi.org/10.1097/CCM.0000000000001951] [PMID: 27513538]
[17]
Billiar, T.R.; Vodovotz, Y. Time for trauma immunology. PLoS Med., 2017, 14(7)e1002342
[http://dx.doi.org/10.1371/journal.pmed.1002342] [PMID: 28700602]
[18]
Hazeldine, J.; Hampson, P.; Lord, J.M. The diagnostic and prognostic value of systems biology research in major traumatic and thermal injury: a review. Burns Trauma, 2016, 4, 33.
[http://dx.doi.org/10.1186/s41038-016-0059-3] [PMID: 27672669]
[19]
Namas, R.; Ghuma, A.; Hermus, L.; Zamora, R.; Okonkwo, D.O.; Billiar, T.R.; Vodovotz, Y. The acute inflammatory response in trauma/hemorrhage and traumatic brain injury: current state and emerging prospects. Libyan J. Med., 2009, 4(3), 97-103.
[http://dx.doi.org/10.3402/ljm.v4i3.4824] [PMID: 21483522]
[20]
Namas, R.A.; Vodovotz, Y.; Almahmoud, K.; Abdul-Malak, O.; Zaaqoq, A.; Namas, R.; Mi, Q.; Barclay, D.; Zuckerbraun, B.; Peitzman, A.B.; Sperry, J.; Billiar, T.R. Temporal patterns of circulating inflammation biomarker networks differentiate susceptibility to nosocomial infection following blunt trauma in humans. Ann. Surg., 2016, 263(1), 191-198.
[http://dx.doi.org/10.1097/SLA.0000000000001001] [PMID: 25371118]
[21]
Bos, L.D.; Sterk, P.J.; Schultz, M.J. Measuring metabolomics in acute lung injury: choosing the correct compartment? Am. J. Respir. Crit. Care Med., 2012, 185(7), 789.
[http://dx.doi.org/10.1164/ajrccm.185.7.789] [PMID: 22467809]
[22]
Fiandaca, M.S.; Mapstone, M.; Mahmoodi, A.; Gross, T.; Macciardi, F.; Cheema, A.K.; Merchant-Borna, K.; Bazarian, J.; Federoff, H.J. Plasma metabolomic biomarkers accurately classify acute mild traumatic brain injury from controls. PLoS One, 2018, 13(4)e0195318
[http://dx.doi.org/10.1371/journal.pone.0195318] [PMID: 29677216]
[23]
Li, H-H. High-throughput metabolomics identifies serum metabolic signatures in acute kidney injury using LC-MS combined with pattern recognition approach. RSC Advances, 2018, 8, 14838-14847.
[http://dx.doi.org/10.1039/C8RA01749B]
[24]
Shah, N.J.; Sureshkumar, S.; Shewade, D.G. Metabolomics: A tool ahead for understanding molecular mechanisms of drugs and diseases. Indian J. Clin. Biochem., 2015, 30(3), 247-254.
[http://dx.doi.org/10.1007/s12291-014-0455-z] [PMID: 26089608]
[25]
Nam, M.; Huh, J.E.; Kim, M.S.; Ryu, D.H.; Park, J.; Kim, H.S.; Lee, S.Y.; Hwang, G.S. Metabolic alterations in the bone tissues of aged osteoporotic mice. Sci. Rep., 2018, 8(1), 8127.
[http://dx.doi.org/10.1038/s41598-018-26322-7] [PMID: 29802267]
[26]
Zhao, Q.; Shen, H.; Su, K.J.; Zhang, J.G.; Tian, Q.; Zhao, L.J.; Qiu, C.; Zhang, Q.; Garrett, T.J.; Liu, J.; Deng, H.W. Metabolomic profiles associated with bone mineral density in US Caucasian women. Nutr. Metab. (Lond.), 2018, 15, 57.
[http://dx.doi.org/10.1186/s12986-018-0296-5] [PMID: 30116286]
[27]
Jayaraman, S.P.; Anand, R.J.; DeAntonio, J.H.; Mangino, M.; Aboutanos, M.B.; Kasirajan, V.; Ivatury, R.R.; Valadka, A.B.; Glushakova, O.; Hayes, R.L.; Bachmann, L.M.; Brophy, G.M.; Contaifer, D.; Warncke, U.O.; Brophy, D.F.; Wijesinghe, D.S. Metabolomics and precision medicine in trauma: The state of the field. Shock, 2018, 50(1), 5-13.
[http://dx.doi.org/10.1097/SHK.0000000000001093] [PMID: 29280924]
[28]
Fabian, T.C. Unraveling the fat embolism syndrome. N. Engl. J. Med., 1993, 329(13), 961-963.
[http://dx.doi.org/10.1056/NEJM199309233291313] [PMID: 8361513]
[29]
Prasad, G.; Dhillon, M.S.; Khullar, M.; Nagi, O.N. Evaluation of oxidative stress after fractures. A preliminary study. Acta Orthop. Belg., 2003, 69(6), 546-551.
[PMID: 14748113]
[30]
Sheweita, S.A.; Khoshhal, K.I. Calcium metabolism and oxidative stress in bone fractures: role of antioxidants. Curr. Drug Metab., 2007, 8(5), 519-525.
[http://dx.doi.org/10.2174/138920007780866852] [PMID: 17584023]
[31]
Loi, F.; Córdova, L.A.; Pajarinen, J.; Lin, T.H.; Yao, Z.; Goodman, S.B. Inflammation, fracture and bone repair. Bone, 2016, 86, 119-130.
[http://dx.doi.org/10.1016/j.bone.2016.02.020] [PMID: 26946132]
[32]
Mountziaris, P.M.; Mikos, A.G. Modulation of the inflammatory response for enhanced bone tissue regeneration. Tissue Eng. Part B Rev., 2008, 14(2), 179-186.
[http://dx.doi.org/10.1089/ten.teb.2008.0038] [PMID: 18544015]
[33]
Mudd, K.L.; Hunt, A.; Matherly, R.C.; Goldsmith, L.J.; Campbell, F.R.; Nichols, G.R., II; Rink, R.D. Analysis of pulmonary fat embolism in blunt force fatalities. J. Trauma, 2000, 48(4), 711-715.
[http://dx.doi.org/10.1097/00005373-200004000-00020] [PMID: 10780606]
[34]
Giannoudis, P.V.; Smith, R.M.; Bellamy, M.C.; Morrison, J.F.; Dickson, R.A.; Guillou, P.J. Stimulation of the inflammatory system by reamed and unreamed nailing of femoral fractures. An analysis of the second hit. J. Bone Joint Surg. Br., 1999, 81(2), 356-361.
[http://dx.doi.org/10.1302/0301-620X.81B2.0810356] [PMID: 10204951]
[35]
Johnson, K.D.; Cadambi, A.; Seibert, G.B. Incidence of adult respiratory distress syndrome in patients with multiple musculoskeletal injuries: effect of early operative stabilization of fractures. J. Trauma, 1985, 25(5), 375-384.
[http://dx.doi.org/10.1097/00005373-198505000-00001] [PMID: 3999159]
[36]
Pape, H.C.; Regel, G.; Dwenger, A.; Krumm, K.; Schweitzer, G.; Krettek, C.; Sturm, J.A.; Tscherne, H. Influences of different methods of intramedullary femoral nailing on lung function in patients with multiple trauma. J. Trauma, 1993, 35(5), 709-716.
[http://dx.doi.org/10.1097/00005373-199311000-00010] [PMID: 8230334]
[37]
Schemitsch, E.H.; Turchin, D.C.; Anderson, G.I.; Byrick, R.J.; Mullen, J.B.; Richards, R.R. Pulmonary and systemic fat embolization after medullary canal pressurization: a hemodynamic and histologic investigation in the dog. J. Trauma, 1998, 45(4), 738-742.
[http://dx.doi.org/10.1097/00005373-199810000-00019] [PMID: 9783613]
[38]
Suto, Y.; Nagata, K.; Ahmed, S.M.; Jacovides, C.; Browne, K.D.; Cognetti, J.; Weber, M.T.; Johnson, V.E.; Leone, R.; Kaplan, L.J.; Smith, D.H.; Pascual, J.L. A concomitant bone fracture delays cognitive recovery from traumatic brain injury. J. Trauma Acute Care Surg., 2018, 85(2), 275-284.
[http://dx.doi.org/10.1097/TA.0000000000001957] [PMID: 29787539]
[39]
Townsend, R.N.; Lheureau, T.; Protech, J.; Riemer, B.; Simon, D. Timing fracture repair in patients with severe brain injury (Glasgow Coma Scale score <9). J. Trauma, 1998, 44(6), 977-982.
[http://dx.doi.org/10.1097/00005373-199806000-00008] [PMID: 9637152]
[40]
Frölke, J.P.; Van de Krol, H.; Bakker, F.C.; Patka, P.; Haarman, H.J. Destination of debris during intramedullary reaming. An experimental study on sheep femurs. Acta Orthop. Belg., 2000, 66(4), 337-340.
[PMID: 11103483]
[41]
Hoegel, F.; Mueller, C.A.; Peter, R.; Pfister, U.; Suedkamp, N.P. Bone debris: dead matter or vital osteoblasts. J. Trauma, 2004, 56(2), 363-367.
[http://dx.doi.org/10.1097/01.TA.0000047811.13196.02] [PMID: 14960981]
[42]
Wenisch, S.; Trinkaus, K.; Hild, A.; Hose, D.; Herde, K.; Heiss, C.; Kilian, O.; Alt, V.; Schnettler, R. Human reaming debris: a source of multipotent stem cells. Bone, 2005, 36(1), 74-83.
[http://dx.doi.org/10.1016/j.bone.2004.09.019] [PMID: 15664005]
[43]
Aoki, S.; Yokoyama, K.; Itoman, M. Effects of reamed or unreamed intramedullary nailing under non-damaged conditions on pulmonary function in sheep. J. Trauma, 2005, 59(3), 647-658.
[PMID: 16361908]
[44]
Giannoudis, P.V.; Tzioupis, C.; Pape, H.C. Fat embolism: the reaming controversy. Injury, 2006, 37(Suppl. 4), S50-S58.
[http://dx.doi.org/10.1016/j.injury.2006.08.040] [PMID: 16990061]
[45]
Ripps, H.; Shen, W. Review: taurine: a “very essential” amino acid. Mol. Vis., 2012, 18, 2673-2686.
[PMID: 23170060]
[46]
Haimovitz-Friedman, A.; Kolesnick, R.N.; Fuks, Z. Ceramide signaling in apoptosis. Br. Med. Bull., 1997, 53(3), 539-553.
[http://dx.doi.org/10.1093/oxfordjournals.bmb.a011629] [PMID: 9374036]
[47]
Maceyka, M.; Spiegel, S. Sphingolipid metabolites in inflammatory disease. Nature, 2014, 510(7503), 58-67.
[http://dx.doi.org/10.1038/nature13475] [PMID: 24899305]
[48]
Davis, I.; Liu, A. What is the tryptophan kynurenine pathway and why is it important to neurotherapeutics? Expert Rev. Neurother., 2015, 15(7), 719-721.
[http://dx.doi.org/10.1586/14737175.2015.1049999] [PMID: 26004930]
[49]
Badawy, A.A. Kynurenine pathway of tryptophan metabolism: Regulatory and functional aspects. Int. J. Tryptophan Res., 2017, 101178646917691938
[http://dx.doi.org/10.1177/1178646917691938] [PMID: 28469468]
[50]
Chen, Y.; Guillemin, G.J. Kynurenine pathway metabolites in humans: disease and healthy States. Int. J. Tryptophan Res., 2009, 2, 1-19.
[http://dx.doi.org/10.4137/IJTR.S2097] [PMID: 22084578]
[51]
Dinçel, E.; Özkan, Y.; Şüküroğlu, M.; Özsoy, H.; Sepici Dinçel, A. Evaluation of Tryptophan/Kynurenine Pathway Relevance With Immune System Biomarkers of Low Energy Trauma Hip Fractures in Osteoporotic Patients. Arch. Rheumatol., 2017, 32(3), 203-208.
[http://dx.doi.org/10.5606/ArchRheumatol.2017.6216] [PMID: 30375548]
[52]
Dehhaghi, M.; Kazemi Shariat Panahi, H.; Guillemin, G.J. Microorganisms, Tryptophan Metabolism, and Kynurenine Pathway: A Complex Interconnected Loop Influencing Human Health Status. Int. J. Tryptophan Res., 2019, 121178646919852996
[http://dx.doi.org/10.1177/1178646919852996] [PMID: 31258331]
[53]
Suarez-Bregua, P.; Guerreiro, P.M.; Rotllant, J. Stress, Glucocorticoids and bone: A review from mammals and fish. Front. Endocrinol. (Lausanne), 2018, 9, 526.
[http://dx.doi.org/10.3389/fendo.2018.00526] [PMID: 30250453]
[54]
Leong, S.C.; Sirich, T.L. Indoxyl sulfate-review of toxicity and therapeutic strategies. Toxins (Basel), 2016, 8(12)E358
[http://dx.doi.org/10.3390/toxins8120358] [PMID: 27916890]
[55]
Zhang, Z.; Rasmussen, L.; Saraswati, M.; Koehler, R.C.; Robertson, C.; Kannan, S. Traumatic injury leads to Inflammation and altered tryptophan metabolism in the juvenile rabbit brain. J. Neurotrauma, 2018.
[PMID: 30019623]
[56]
Smirnova, G.; Muzyka, N.; Oktyabrsky, O. Transmembrane glutathione cycling in growing Escherichia coli cells. Microbiol. Res., 2012, 167(3), 166-172.
[http://dx.doi.org/10.1016/j.micres.2011.05.005] [PMID: 21689911]
[57]
Zhang, Z.; Liu, D.; Yi, B.; Liao, Z.; Tang, L.; Yin, D.; He, M. Taurine supplementation reduces oxidative stress and protects the liver in an iron-overload murine model. Mol. Med. Rep., 2014, 10(5), 2255-2262.
[http://dx.doi.org/10.3892/mmr.2014.2544] [PMID: 25201602]
[58]
Jong, C.J.; Ito, T.; Prentice, H.; Wu, J.Y.; Schaffer, S.W. Role of mitochondria and endoplasmic reticulum in taurine-deficiency-mediated apoptosis. Nutrients, 2017, 9(8)E795
[http://dx.doi.org/10.3390/nu9080795] [PMID: 28757580]
[59]
Hansen, S.H.; Andersen, M.L.; Cornett, C.; Gradinaru, R.; Grunnet, N. A role for taurine in mitochondrial function. J. Biomed. Sci., 2010, 17(Suppl. 1), S23.
[http://dx.doi.org/10.1186/1423-0127-17-S1-S23] [PMID: 20804598]
[60]
Moseley, R.; Stewart, J.E.; Stephens, P.; Waddington, R.J.; Thomas, D.W. Extracellular matrix metabolites as potential biomarkers of disease activity in wound fluid: lessons learned from other inflammatory diseases? Br. J. Dermatol., 2004, 150(3), 401-413.
[http://dx.doi.org/10.1111/j.1365-2133.2004.05845.x] [PMID: 15030321]
[61]
Moriarity, J.L.; Hurt, K.J.; Resnick, A.C.; Storm, P.B.; Laroy, W.; Schnaar, R.L.; Snyder, S.H. UDP-glucuronate decarboxylase, a key enzyme in proteoglycan synthesis: cloning, characterization, and localization. J. Biol. Chem., 2002, 277(19), 16968-16975.
[http://dx.doi.org/10.1074/jbc.M109316200] [PMID: 11877387]
[62]
Jerosch, J. Effects of Glucosamine and chondroitin sulfate on cartilage metabolism in OA: Outlook on other nutrient partners especially omega-3 fatty acids. Int. J. Rheumatol., 2011, 2011969012
[http://dx.doi.org/10.1155/2011/969012] [PMID: 21826146]
[63]
Chen, J.K.; Shen, C.R.; Liu, C.L. N-acetylglucosamine: production and applications. Mar. Drugs, 2010, 8(9), 2493-2516.
[http://dx.doi.org/10.3390/md8092493] [PMID: 20948902]
[64]
Menni, C.; Migaud, M.; Glastonbury, C.A.; Beaumont, M.; Nikolaou, A.; Small, K.S.; Brosnan, M.J.; Mohney, R.P.; Spector, T.D.; Valdes, A.M. Metabolomic profiling to dissect the role of visceral fat in cardiometabolic health. Obesity (Silver Spring), 2016, 24(6), 1380-1388.
[http://dx.doi.org/10.1002/oby.21488] [PMID: 27129722]
[65]
Mihalas, B.P.; De Iuliis, G.N.; Redgrove, K.A.; McLaughlin, E.A.; Nixon, B. The lipid peroxidation product 4-hydroxynonenal contributes to oxidative stress-mediated deterioration of the ageing oocyte. Sci. Rep., 2017, 7(1), 6247.
[http://dx.doi.org/10.1038/s41598-017-06372-z] [PMID: 28740075]
[66]
Isseroff, R.R.; Ziboh, V.A.; Chapkin, R.S.; Martinez, D.T. Conversion of linoleic acid into arachidonic acid by cultured murine and human keratinocytes. J. Lipid Res., 1987, 28(11), 1342-1349.
[PMID: 2448410]
[67]
Yui, K.; Imataka, G.; Nakamura, H.; Ohara, N.; Naito, Y. Eicosanoids derived from arachidonic acid and their family prostaglandins and cyclooxygenase in psychiatric disorders. Curr. Neuropharmacol., 2015, 13(6), 776-785.
[http://dx.doi.org/10.2174/1570159X13666151102103305] [PMID: 26521945]
[68]
Salari, H.; Braquet, P.; Borgeat, P. Stimulation of lipoxygenase product synthesis in human leukocytes and platelets by melittin. Mol. Pharmacol., 1985, 28(6), 546-548.
[PMID: 3935909]
[69]
Hannibal, K.E.; Bishop, M.D. Chronic stress, cortisol dysfunction, and pain: a psychoneuroendocrine rationale for stress management in pain rehabilitation. Phys. Ther., 2014, 94(12), 1816-1825.
[http://dx.doi.org/10.2522/ptj.20130597] [PMID: 25035267]
[70]
Prakash, S.; Sen, R.K.; Tripathy, S.K.; Sen, I.M.; Sharma, R.R.; Sharma, S. Role of interleukin-6 as an early marker of fat embolism syndrome: a clinical study. Clin. Orthop. Relat. Res., 2013, 471(7), 2340-2346.
[http://dx.doi.org/10.1007/s11999-013-2869-y] [PMID: 23423626]


open access plus

Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 7
ISSUE: 1
Year: 2020
Published on: 06 September, 2020
Page: [51 - 66]
Pages: 16
DOI: 10.2174/2666338407666191204111457

Article Metrics

PDF: 16
HTML: 1