Skip to main content
Top
Published in: Journal of Thrombosis and Thrombolysis 1/2023

15-11-2022

l-carnitine modulates free mitochondrial DNA DAMPs and platelet storage lesions during storage of platelet concentrates

Authors: Saeede Bagheri, Shahram Samiee, Mahin Nikougoftar Zarif, Mohammad Reza Deyhim

Published in: Journal of Thrombosis and Thrombolysis | Issue 1/2023

Login to get access

Abstract

Platelet storage lesions may occur in Platelet concentrates (PCs) storage time, reducing PCs' quality. Mitochondrial damage causes mitochondrial DNA (mtDNA) to be released into the extracellular space. In this study, we evaluated the effect of l-carnitine (LC) as an antioxidant on free mtDNA DAMPs release in PCs during storage. Ten PCs prepared by the PRP method were studied. The copy numbers of free mtDNA, total reactive oxygen species (ROS), lactate dehydrogenase (LDH) enzyme activity, pH, and platelet counts were measured on days 0, 3, 5, and 7 of PCs storage in LC-treated and untreated platelets. LDH activity was significantly lower than the control group during 7 days of PCs storage (p = 0.041). Also, ROS production decreased in LC-treated PCs compared to the control group during storage (p = 0.026), and the difference mean of ROS between the two groups was significant on day 3, 5, and 7 (Pday3 = 0.02, Pday5 = 0.0001, Pday7 = 0.031). Moreover, LC decreased the copy numbers of free mtDNA during 7 days of storage (p = 0.021), and the difference mean of the copy numbers of free mtDNA in LC-treated PCs compared to the control group was significant on day 5 and 7 (Pday5 = 0.041، Pday7 = 0.022). It seems that LC can maintain the metabolism and antioxidant capacity of PCs and thus can reduce mitochondrial damage and mtDNA release; consequently, it can decrease DAMPs in PCs. Therefore, it may be possible to use this substance as a platelet additive solution in the future.
Appendix
Available only for authorised users
Literature
4.
go back to reference Al Amir Dache Z, Otandault A, Tanos R, Pastor B, Meddeb R, Sanchez C et al (2020) Blood contains circulating cell-free respiratory competent mitochondria. FASEB J 34(3):3616–3630CrossRefPubMed Al Amir Dache Z, Otandault A, Tanos R, Pastor B, Meddeb R, Sanchez C et al (2020) Blood contains circulating cell-free respiratory competent mitochondria. FASEB J 34(3):3616–3630CrossRefPubMed
5.
go back to reference Marchi S, Giorgi C, Suski JM, Agnoletto C, Bononi A, Bonora M et al (2012) Mitochondria-ros crosstalk in the control of cell death and aging. J Signal Transduct 2012:1–17CrossRef Marchi S, Giorgi C, Suski JM, Agnoletto C, Bononi A, Bonora M et al (2012) Mitochondria-ros crosstalk in the control of cell death and aging. J Signal Transduct 2012:1–17CrossRef
6.
go back to reference Orrenius S (2007) Reactive oxygen species in mitochondria-mediated cell death. Drug Metab Rev 39(2–3):443–455CrossRefPubMed Orrenius S (2007) Reactive oxygen species in mitochondria-mediated cell death. Drug Metab Rev 39(2–3):443–455CrossRefPubMed
7.
go back to reference Schulz E, Wenzel P, Münzel T, Daiber A (2014) Mitochondrial redox signaling: interaction of mitochondrial reactive oxygen species with other sources of oxidative stress. Antioxid Redox Signal 20(2):308–324CrossRefPubMedCentralPubMed Schulz E, Wenzel P, Münzel T, Daiber A (2014) Mitochondrial redox signaling: interaction of mitochondrial reactive oxygen species with other sources of oxidative stress. Antioxid Redox Signal 20(2):308–324CrossRefPubMedCentralPubMed
9.
go back to reference Freedman JE, Loscalzo J, Barnard MR, Alpert C, Keaney J, Michelson AD (1997) Nitric oxide released from activated platelets inhibits platelet recruitment. J Clin Investig 100(2):350–356CrossRefPubMedCentralPubMed Freedman JE, Loscalzo J, Barnard MR, Alpert C, Keaney J, Michelson AD (1997) Nitric oxide released from activated platelets inhibits platelet recruitment. J Clin Investig 100(2):350–356CrossRefPubMedCentralPubMed
10.
go back to reference Villarroel JPP, Figueredo R, Guan Y, Tomaiuolo M, Karamercan MA, Welsh J et al (2013) Increased platelet storage time is associated with mitochondrial dysfunction and impaired platelet function. J Surg Res 184(1):422–429CrossRef Villarroel JPP, Figueredo R, Guan Y, Tomaiuolo M, Karamercan MA, Welsh J et al (2013) Increased platelet storage time is associated with mitochondrial dysfunction and impaired platelet function. J Surg Res 184(1):422–429CrossRef
11.
go back to reference Marcoux G, Duchez A-C, Rousseau M, Lévesque T, Boudreau LH, Thibault L et al (2017) Microparticle and mitochondrial release during extended storage of different types of platelet concentrates. Platelets 28(3):272–280CrossRefPubMed Marcoux G, Duchez A-C, Rousseau M, Lévesque T, Boudreau LH, Thibault L et al (2017) Microparticle and mitochondrial release during extended storage of different types of platelet concentrates. Platelets 28(3):272–280CrossRefPubMed
12.
go back to reference Skulachev VP (1999) Mitochondrial physiology and pathology; concepts of programmed death of organelles, cells and organisms. Mol Aspects Med 20(3):139–184CrossRefPubMed Skulachev VP (1999) Mitochondrial physiology and pathology; concepts of programmed death of organelles, cells and organisms. Mol Aspects Med 20(3):139–184CrossRefPubMed
13.
go back to reference Magron A, Laugier J, Provost P, Boilard E (2018) Pathogen reduction technologies: the pros and cons for platelet transfusion. Platelets 29(1):2–8CrossRefPubMed Magron A, Laugier J, Provost P, Boilard E (2018) Pathogen reduction technologies: the pros and cons for platelet transfusion. Platelets 29(1):2–8CrossRefPubMed
14.
go back to reference Boudreau LH, Duchez A-C, Cloutier N, Soulet D, Martin N, Bollinger J et al (2014) Platelets release mitochondria serving as substrate for bactericidal group IIA-secreted phospholipase A2 to promote inflammation. Blood 124(14):2173–2183CrossRefPubMedCentralPubMed Boudreau LH, Duchez A-C, Cloutier N, Soulet D, Martin N, Bollinger J et al (2014) Platelets release mitochondria serving as substrate for bactericidal group IIA-secreted phospholipase A2 to promote inflammation. Blood 124(14):2173–2183CrossRefPubMedCentralPubMed
15.
go back to reference Marcoux G, Boilard E (2017) Mitochondrial damage-associated molecular patterns in blood transfusion products. ISBT Sci Ser 12(4):501–505CrossRef Marcoux G, Boilard E (2017) Mitochondrial damage-associated molecular patterns in blood transfusion products. ISBT Sci Ser 12(4):501–505CrossRef
16.
go back to reference Yasui K, Matsuyama N, Kuroishi A, Tani Y, Furuta RA, Hirayama F (2016) Mitochondrial damage-associated molecular patterns as potential proinflammatory mediators in post–platelet transfusion adverse effects. Transfusion 56(5):1201–1212CrossRefPubMed Yasui K, Matsuyama N, Kuroishi A, Tani Y, Furuta RA, Hirayama F (2016) Mitochondrial damage-associated molecular patterns as potential proinflammatory mediators in post–platelet transfusion adverse effects. Transfusion 56(5):1201–1212CrossRefPubMed
17.
go back to reference Slichter SJ, Corson J, Jones MK, Christoffel T, Pellham E, Bailey SL et al (2014) Exploratory studies of extended storage of apheresis platelets in a platelet additive solution (PAS). Blood 123(2):271–280CrossRefPubMedCentralPubMed Slichter SJ, Corson J, Jones MK, Christoffel T, Pellham E, Bailey SL et al (2014) Exploratory studies of extended storage of apheresis platelets in a platelet additive solution (PAS). Blood 123(2):271–280CrossRefPubMedCentralPubMed
18.
go back to reference Steiber A, Kerner J, Hoppel CL (2004) Carnitine: a nutritional, biosynthetic, and functional perspective. Mol Aspects Med 25(5–6):455–473CrossRefPubMed Steiber A, Kerner J, Hoppel CL (2004) Carnitine: a nutritional, biosynthetic, and functional perspective. Mol Aspects Med 25(5–6):455–473CrossRefPubMed
18.
go back to reference Demarquoy J (2011) L-carnitine: structure and function. eLS. CRC Press, Boca Raton Demarquoy J (2011) L-carnitine: structure and function. eLS. CRC Press, Boca Raton
20.
go back to reference Sandgren P, Stjepanovic A (2012) High-yield platelet units revealed immediate pH decline and delayed mitochondrial dysfunction during storage in 100% plasma as compared with storage in SSP+. Vox Sang 103(1):55–63CrossRefPubMed Sandgren P, Stjepanovic A (2012) High-yield platelet units revealed immediate pH decline and delayed mitochondrial dysfunction during storage in 100% plasma as compared with storage in SSP+. Vox Sang 103(1):55–63CrossRefPubMed
21.
go back to reference Deyhim M, Mesbah-Namin S, Khoshnaghsh F (2020) Protective effect of L-carnitine on platelet apoptosis during storage of platelet concentrate. Transfus Clin Biol 27(3):139–146CrossRefPubMed Deyhim M, Mesbah-Namin S, Khoshnaghsh F (2020) Protective effect of L-carnitine on platelet apoptosis during storage of platelet concentrate. Transfus Clin Biol 27(3):139–146CrossRefPubMed
22.
go back to reference Najafi M, Garjani A, Doustar Y (2007) Effects of L-carnitine on cardiac apoptosis in ischemic-reperfused isolated rat heart Najafi M, Garjani A, Doustar Y (2007) Effects of L-carnitine on cardiac apoptosis in ischemic-reperfused isolated rat heart
23.
go back to reference Ye J, Li J, Yu Y, Wei Q, Deng W, Yu L (2010) L-carnitine attenuates oxidant injury in HK-2 cells via ROS-mitochondria pathway. Regul Pept 161(1–3):58–66CrossRefPubMed Ye J, Li J, Yu Y, Wei Q, Deng W, Yu L (2010) L-carnitine attenuates oxidant injury in HK-2 cells via ROS-mitochondria pathway. Regul Pept 161(1–3):58–66CrossRefPubMed
24.
go back to reference Naghadeh HT, Badlou BA, Ferizhandy AS, Mohammadreza TS, Shahram V (2013) Six hours of resting platelet concentrates stored at 22–24 ºC for 48 hours in permeable bags preserved pH, swirling and lactate dehydrogenase better and caused less platelet activation. Blood Transfus 11(3):400PubMedCentralPubMed Naghadeh HT, Badlou BA, Ferizhandy AS, Mohammadreza TS, Shahram V (2013) Six hours of resting platelet concentrates stored at 22–24 ºC for 48 hours in permeable bags preserved pH, swirling and lactate dehydrogenase better and caused less platelet activation. Blood Transfus 11(3):400PubMedCentralPubMed
25.
go back to reference Surai PF (2015) Antioxidant action of carnitine: molecular mechanisms and practical applications. EC Vet Sci 2(1):66–84 Surai PF (2015) Antioxidant action of carnitine: molecular mechanisms and practical applications. EC Vet Sci 2(1):66–84
25.
go back to reference Roback J, Grossman B, Harris T, Hillier C (2011) Technical manual, 17th edn. AABB, Bethesda, p 220 Roback J, Grossman B, Harris T, Hillier C (2011) Technical manual, 17th edn. AABB, Bethesda, p 220
26.
go back to reference Manasa K, Vani R (2016) Influence of oxidative stress on stored platelets. Adv Hematol 2016:1–6CrossRef Manasa K, Vani R (2016) Influence of oxidative stress on stored platelets. Adv Hematol 2016:1–6CrossRef
28.
go back to reference Saluk-Juszczak J, Olas B, Wachowicz B, Glowacki R, Bald E (2010) L-carnitine modulates blood platelet oxidative stress. Cell Biol Toxicol 26(4):355–365CrossRefPubMed Saluk-Juszczak J, Olas B, Wachowicz B, Glowacki R, Bald E (2010) L-carnitine modulates blood platelet oxidative stress. Cell Biol Toxicol 26(4):355–365CrossRefPubMed
29.
go back to reference Dayanand C, Krishnamurthy N, Ashakiran S, Shashidhar K (2011) Carnitine: a novel health factor–an overview. Int J Pharm Biomed Res 2(2):79–89 Dayanand C, Krishnamurthy N, Ashakiran S, Shashidhar K (2011) Carnitine: a novel health factor–an overview. Int J Pharm Biomed Res 2(2):79–89
30.
go back to reference Pignatelli P, Lenti L, Sanguigni V, Frati G, Simeoni I, Gazzaniga P et al (2003) Carnitine inhibits arachidonic acid turnover, platelet function, and oxidative stress. Am J Physiol Heart Circul Physiol 284(1):H41–H48CrossRef Pignatelli P, Lenti L, Sanguigni V, Frati G, Simeoni I, Gazzaniga P et al (2003) Carnitine inhibits arachidonic acid turnover, platelet function, and oxidative stress. Am J Physiol Heart Circul Physiol 284(1):H41–H48CrossRef
31.
go back to reference Cognasse F, Aloui C, Anh Nguyen K, Hamzeh-Cognasse H, Fagan J, Arthaud CA et al (2016) Platelet components associated with adverse reactions: predictive value of mitochondrial DNA relative to biological response modifiers. Transfusion 56(2):497–504CrossRefPubMed Cognasse F, Aloui C, Anh Nguyen K, Hamzeh-Cognasse H, Fagan J, Arthaud CA et al (2016) Platelet components associated with adverse reactions: predictive value of mitochondrial DNA relative to biological response modifiers. Transfusion 56(2):497–504CrossRefPubMed
32.
go back to reference Amiri F, Dahaj MM, Siasi NH, Deyhim MR (2021) Treatment of platelet concentrates with the L-carnitine modulates platelets oxidative stress and platelet apoptosis due to mitochondrial reactive oxygen species reduction and reducing cytochrome C release during storage. J Thromb Thrombolysis 51(2):277–285CrossRefPubMed Amiri F, Dahaj MM, Siasi NH, Deyhim MR (2021) Treatment of platelet concentrates with the L-carnitine modulates platelets oxidative stress and platelet apoptosis due to mitochondrial reactive oxygen species reduction and reducing cytochrome C release during storage. J Thromb Thrombolysis 51(2):277–285CrossRefPubMed
33.
go back to reference Dean WL, Lee MJ, Cummins TD, Schultz DJ, Powell DW (2009) Proteomic and functional characterisation of platelet microparticle size classes. Thromb Haemost 102(10):711–718CrossRefPubMedCentralPubMed Dean WL, Lee MJ, Cummins TD, Schultz DJ, Powell DW (2009) Proteomic and functional characterisation of platelet microparticle size classes. Thromb Haemost 102(10):711–718CrossRefPubMedCentralPubMed
34.
go back to reference Sweeney JD, Blair AJ, Cheves TA, Dottori S, Arduini A (2000) l-carnitine decreases glycolysis in liquid-stored platelets. Transfusion 40(11):1313–1319CrossRefPubMed Sweeney JD, Blair AJ, Cheves TA, Dottori S, Arduini A (2000) l-carnitine decreases glycolysis in liquid-stored platelets. Transfusion 40(11):1313–1319CrossRefPubMed
35.
go back to reference Lee Y-L, King MB, Gonzalez RP, Brevard SB, Frotan MA, Gillespie MN et al (2014) Blood transfusion products contain mitochondrial DNA damage-associated molecular patterns: a potential effector of transfusion-related acute lung injury. J Surg Res 191(2):286–289CrossRefPubMedCentralPubMed Lee Y-L, King MB, Gonzalez RP, Brevard SB, Frotan MA, Gillespie MN et al (2014) Blood transfusion products contain mitochondrial DNA damage-associated molecular patterns: a potential effector of transfusion-related acute lung injury. J Surg Res 191(2):286–289CrossRefPubMedCentralPubMed
36.
go back to reference Velashjerdi Z, Deyhim M, Razjou F, Eydi A (2018) Effect of L-carnitine on platelet bacterial contamination and platelet metabolism during 5 days of storage of platelet concentrates. Sci J Iran Blood Transfus Organ 15(1):1–11 Velashjerdi Z, Deyhim M, Razjou F, Eydi A (2018) Effect of L-carnitine on platelet bacterial contamination and platelet metabolism during 5 days of storage of platelet concentrates. Sci J Iran Blood Transfus Organ 15(1):1–11
37.
go back to reference Deyhim MR, Mesbah-Namin SA, Yari F, Taghikhani M, Amirizadeh N (2015) L-carnitine effectively improves the metabolism and quality of platelet concentrates during storage. Ann Hematol 94(4):671–680CrossRefPubMed Deyhim MR, Mesbah-Namin SA, Yari F, Taghikhani M, Amirizadeh N (2015) L-carnitine effectively improves the metabolism and quality of platelet concentrates during storage. Ann Hematol 94(4):671–680CrossRefPubMed
Metadata
Title
l-carnitine modulates free mitochondrial DNA DAMPs and platelet storage lesions during storage of platelet concentrates
Authors
Saeede Bagheri
Shahram Samiee
Mahin Nikougoftar Zarif
Mohammad Reza Deyhim
Publication date
15-11-2022
Publisher
Springer US
Published in
Journal of Thrombosis and Thrombolysis / Issue 1/2023
Print ISSN: 0929-5305
Electronic ISSN: 1573-742X
DOI
https://doi.org/10.1007/s11239-022-02725-2

Other articles of this Issue 1/2023

Journal of Thrombosis and Thrombolysis 1/2023 Go to the issue