bloodjourГематология и трансфузиологияRussian journal of hematology and transfusiology0234-57302411-3042ООО Издательский дом «Практика»10.35754/0234-5730-2022-67-1-62-73bloodjour-337Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESВлияние низкой концентрации мелатонина на качество хранимых эритроцитов in vitroEffect of low concentration of melatonin on the quality of stored red blood cells in vitroLiS.LiS.

Баотоу

Baotou

ZhangL.ZhangL.

Баотоу

Baotou

YuanH.YuanH.

Баотоу

Baotou

YangL.YangL.

Баотоу

Baotou

SongF.SongF.

Баотоу

Baotou

LiuH.LiuH.

Баотоу

Baotou

WeiC.WeiC.

Баотоу

Baotou

DingH.DingH.

Баотоу

Baotou

MaQ.MaQ.

Баотоу

31 Jianshe Road, Baotou, Inner Mongolia.

ximenzi4554@sina.comSuY.SuY.

31 Jianshe Road, Baotou, Inner Mongolia, China

 

31 Jianshe Road, Baotou, Inner Mongolia.

synmg@126.comИнститут консервации крови, Медицинский колледж БаотоуКитайInstitute of Blood Conservation, Baotou Medical CollegeChinaОтделение сбора крови, Центральная станция кровиКитайDepartment of Blood Collection, Baotou Central Blood StationChinaОтделение гистологии и эмбриологии, Медицинский колледж БаотоуКитайDepartment of Histology and Embryology, Baotou Medical CollegeChinaОтделение ортопедии, Первая аффилированная больница Медицинского колледжа БаотоуКитайDepartment of Orthopedics, the First Affi liated Hospital of Baotou Medical CollegeChina2022110420226716273Copyright © Li S., Zhang L., Yuan H., Yang L., Song F., Liu H., Wei C., Ding H., Ma Q., Su Y., 20222022Li S., Zhang L., Yuan H., Yang L., Song F., Liu H., Wei C., Ding H., Ma Q., Su Y.Li S., Zhang L., Yuan H., Yang L., Song F., Liu H., Wei C., Ding H., Ma Q., Su Y.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.htjournal.ru/jour/article/view/337Введение

Введение. Окислительный стресс является одной из причин повреждения эритроцитов при хранении. Мелатонин (МТ) является эффективным антиоксидантом, однако про- и антиоксидантные свойства МТ зависят от типа клеток, окислительно-восстановительного состояния, а также экспериментальных условий.

Цель работы — изучить влияние низкой концентрации МТ на морфологию, агрегацию, окислительный стресс и метаболизм глюкозы эритроцитов при их долговременном хранении. Материалы и методы. Лейкофильтрованные эритроциты инкубировали в течение 42 дней в условиях банка крови в добавочной среде МАР с МТ (150  пг/мл) и без МТ. Для выявления протективного эффекта МТ при хранении эритроцитов изучали морфологию эритроцитов, агрегационный индекс, концентрации метгемоглобина (MetHb), малонового диальдегида (MДA), глюкозы, мочевой кислоты и АТФ в эритроцитах в дни 0, 7, 14, 21, 28, 35 и 42.

Результаты

Результаты. На количество деформированных эритроцитов, относительную скорость гемолиза, индекс агрегации, концентрации MДA и MetHb значительно влияли как время хранения (p < 0,0001), так и наличие мелатонина (p < 0,01), их взаимное действие влияло только на количество деформированных эритроцитов (p < 0,0001). На концентрацию глюкозы, молочной кислоты и АТФ влияло время хранения (p < 0,0001), но не концентрация МТ (p > 0,05). Количество деформированных эритроцитов, относительная скорость гемолиза, MДA и MetHb в группе МТ были значительно ниже, чем в контрольной группе в конце срока хранения (p < 0,05).

Заключение

Заключение. Низкие концентрации МТ оказывали протективный эффект на качество хранимых эритроцитов благодаря антиоксидантному эффекту. 

Introduction

Introduction. Oxidative stress is one of the important causes of red blood cells (RBCs) storage lesion. As a hormone, melatonin (MT) is also an effective antioxidant, however the pro- and antioxidative properties of MT depend on the cell type, redox state, as well as experimental conditions.

Aim of this study — to investigate the protective effects of low concentration of MT on the stored RBCs in vitro.

Materials and methods

Materials and methods. Leukofi ltered RBCs were incubated in MAP RBC additive solution with or without 150 pg/mL of MT for 42 days under blood bank conditions. The morphology, aggregation index, methemoglobin (MetHb), m alondialdehyde (MDA), glucose, lactic acid and ATP of RBCs were detected on days 0, 7, 14, 21, 28, 35 and 42 to observe the protective effects of MT during the storage of RBCs.

Results

Results. During RBCs s torage, the number of deformed RBCs, relative hemolysis rate, aggregation index, MDA and MetHb were signifi cantly affected by both storage time (p  <  0.0001) and melatonin (p  <  0.01), and they had interaction only on the number of deformed RBCs (p < 0.0001). The concentration of glucose, lactic acid and ATP were affected by storage time (p < 0.0001), but not by MT concentration (p > 0.05). The number of deformed RBCs, relative hemolysis rate, MDA and MetHb in MT group were signifi cantly lower than that in control group at the end of storage stage (p < 0.05).

Conclusion

Conclusion. Our study showed low hypnotic drug concentration of MT is speculated to have protective effects on the quality of stored RBCs through antioxidative mechanism. 

мелатонинэритроцитыхранение эритроцитовантиоксидантыэнергетический метаболизмmelatoninred blood cells·blood storage·antioxidationenergy metabolismАвторы благодарят Национальный фонд естественныхнаукКитая (81860029); Научно-исследовательский проект в области медицины и планирования семьи во Внутренней Монголии (201701090); проект группы талантов «Грассленд» автономного районаВнутренняя Монголия; Естественно-научный фонд Внутренней Монголии (2020MS08008) за финансовую поддержку и добровольцев, пожертвовавших кровь для наших исследований. Авторы также благодарят Qiaomei Yan и Shiqi Huang за их отличную техническую помощь.ReferencesD’Alessandro A., Zimring J.C., Busch M. Chronological storage age and metabolic age of stored red blood cells: are they the same? Transfusion. 2019; 59(5): 1620–3. DOI: 10.1111/trf.15248.D’Alessandro A., Zimring J.C., Busch M. Chronological storage age and metabolic age of stored red blood cells: are they the same? Transfusion. 2019; 59(5): 1620–3. DOI: 10.1111/trf.15248.Yoshida T., Prudent M., D’Alessandro A. Red blood cell storage lesion: Causes and potential clinical consequences. Blood Transfus. 2019; 17(1): 27–52. DOI: 10.2450/2019.0217-18.Yoshida T., Prudent M., D’Alessandro A. Red blood cell storage lesion: Causes and potential clinical consequences. Blood Transfus. 2019; 17(1): 27–52. DOI: 10.2450/2019.0217-18.Koch C.G., Figueroa P.I., Li L., et al. Red blood cell storage: How long is too long? Ann Thorac Surg. 2013; 96(5): 1894–9. DOI: 10.1016/j.athoracsur.2013.05.116.Koch C.G., Figueroa P.I., Li L., et al. Red blood cell storage: How long is too long? Ann Thorac Surg. 2013; 96(5): 1894–9. DOI: 10.1016/j.athoracsur.2013.05.116.D’Alessandro A., Kriebardis A.G., Rinalducci S., et al. An update on red blood cell storage lesions, as gleaned through biochemistry and omics technologies. Transfusion. 2015; 55(1): 205–19. Doi: 10.1111/trf.12804.D’Alessandro A., Kriebardis A.G., Rinalducci S., et al. An update on red blood cell storage lesions, as gleaned through biochemistry and omics technologies. Transfusion. 2015; 55(1): 205–19. Doi: 10.1111/trf.12804.Silva C.A.L., Azevedo Filho C.A., Pereira G., et al. Vitamin E nanoemulsion activity on stored red blood cells. Transfus Med. 2017; 27(3): 213–7. DOI: 10.1111/tme.12394.Silva C.A.L., Azevedo Filho C.A., Pereira G., et al. Vitamin E nanoemulsion activity on stored red blood cells. Transfus Med. 2017; 27(3): 213–7. DOI: 10.1111/tme.12394.Stowell S.R., Smith N.H., Zimring J.C., et al. Addition of ascorbic acid solution to stored murine red blood cells increases posttransfusion recovery and decreases microparticles and alloimmunization. Transfusion. 2013; 53(10): 2248–57. DOI: 10.1111/trf.12106.Stowell S.R., Smith N.H., Zimring J.C., et al. Addition of ascorbic acid solution to stored murine red blood cells increases posttransfusion recovery and decreases microparticles and alloimmunization. Transfusion. 2013; 53(10): 2248–57. DOI: 10.1111/trf.12106.Fontes J.A., Banerjee U., Iazbik M.C., et al. Effect of ascorbic acid on storage of Greyhound erythrocytes. Am J Vet Res. 2015; 76(9): 789–800. DOI: 10.2460/ajvr.76.9.789.Fontes J.A., Banerjee U., Iazbik M.C., et al. Effect of ascorbic acid on storage of Greyhound erythrocytes. Am J Vet Res. 2015; 76(9): 789–800. DOI: 10.2460/ajvr.76.9.789.van’t Erve T.J., Doskey C.M., Wagner B.A., et al. Heritability of glutathione and related metabolites in stored red blood cells. Free Radic Biol Med. 2014; 76: 107–13. DOI: 10.1016/j.freeradbiomed.2014.07.040.van’t Erve T.J., Doskey C.M., Wagner B.A., et al. Heritability of glutathione and related metabolites in stored red blood cells. Free Radic Biol Med. 2014; 76: 107–13. DOI: 10.1016/j.freeradbiomed.2014.07.040.Dumaswala U.J., Wilson M.J., Wu Y.L., et al. Glutathione loading prevents free radical injury in red blood cells after storage. Free Radic Res. 2000; 33(5): 517–29. DOI: 10.1080/10715760000301061.Dumaswala U.J., Wilson M.J., Wu Y.L., et al. Glutathione loading prevents free radical injury in red blood cells after storage. Free Radic Res. 2000; 33(5): 517–29. DOI: 10.1080/10715760000301061.Pallotta V., Gevi F., D’Alessandro A., Zolla L. Storing red blood cells with vitamin C and N-acetylcysteine prevents oxidative stress-related lesions: A metabolomics overview. Blood Transfus. 2014; 12(3): 376–87. DOI: 10.2450/2014.0266-13.Pallotta V., Gevi F., D’Alessandro A., Zolla L. Storing red blood cells with vitamin C and N-acetylcysteine prevents oxidative stress-related lesions: A metabolomics overview. Blood Transfus. 2014; 12(3): 376–87. DOI: 10.2450/2014.0266-13.Şekeroğlu M.R., Huyut Z., Him A. The susceptibility of erythrocytes to oxidation during storage of blood: Effects of melatonin and propofol. Clin Biochem. 2012; 45(4-5): 315–9. DOI: 10.1016/j.clinbiochem.2011.12.021.Şekeroğlu M.R., Huyut Z., Him A. The susceptibility of erythrocytes to oxidation during storage of blood: Effects of melatonin and propofol. Clin Biochem. 2012; 45(4-5): 315–9. DOI: 10.1016/j.clinbiochem.2011.12.021.Czubak K., Antosik A., Cichon N., Zbikowska H.M. Vitamin C and Trolox decrease oxidative stress and hemolysis in cold-stored human red blood cells. Redox Rep. 2017; 22(6): 445–50. DOI: 10.1080/13510002.2017.1289314.Czubak K., Antosik A., Cichon N., Zbikowska H.M. Vitamin C and Trolox decrease oxidative stress and hemolysis in cold-stored human red blood cells. Redox Rep. 2017; 22(6): 445–50. DOI: 10.1080/13510002.2017.1289314.Dumaswala U.J., Zhuo L., Mahajan S., et al. Glutathione protects chemokine scavenging and antioxidative defense functions in human RBCs. Am J Physiol Cell Physiol. 2001; 280(4): C867–73. DOI: 10.1152/ajpcell.2001.280.4.C867.Dumaswala U.J., Zhuo L., Mahajan S., et al. Glutathione protects chemokine scavenging and antioxidative defense functions in human RBCs. Am J Physiol Cell Physiol. 2001; 280(4): C867–73. DOI: 10.1152/ajpcell.2001.280.4.C867.Quintana C., Cabrera J., Perdomo J., et al. Melatonin enhances hyperthermia induced apoptotic cell death in human leukemia cells. J Pineal Res. 2016; 61(3): 381–95. DOI: 10.1111/jpi.12356.Quintana C., Cabrera J., Perdomo J., et al. Melatonin enhances hyperthermia induced apoptotic cell death in human leukemia cells. J Pineal Res. 2016; 61(3): 381–95. DOI: 10.1111/jpi.12356.Tan D.X., Manchester L.C., Hardeland R., et al. Melatonin: A hormone, a tissue factor, an autocoid, a paracoid, and an antioxidant vitamin. J Pineal Res. 2003; 34(1): 75–8. DOI: 10.1034/j.1600-079x.2003.02111.x.Tan D.X., Manchester L.C., Hardeland R., et al. Melatonin: A hormone, a tissue factor, an autocoid, a paracoid, and an antioxidant vitamin. J Pineal Res. 2003; 34(1): 75–8. DOI: 10.1034/j.1600-079x.2003.02111.x.Reiter R.J. Pineal melatonin: Cell biology of its synthesis and of its physiological interactions. Endocr Rev. 1991; 12(2): 151–80. D OI: 10.1210/edrv-12-2-151.Reiter R.J. Pineal melatonin: Cell biology of its synthesis and of its physiological interactions. Endocr Rev. 1991; 12(2): 151–80. D OI: 10.1210/edrv-12-2-151.Krokosz A., Grebowski J., Szweda-Lewandowska Z., et al. Can melatonin delay oxidative damage of human erythrocytes during prolonged incubation? Adv Med Sci. 2013; 58(1): 134–42. DOI: 10.2478/v10039-012-0067-x.Krokosz A., Grebowski J., Szweda-Lewandowska Z., et al. Can melatonin delay oxidative damage of human erythrocytes during prolonged incubation? Adv Med Sci. 2013; 58(1): 134–42. DOI: 10.2478/v10039-012-0067-x.Zhang L., Han X., Du H., et al. Identifi cation of melatonin poisoning markers in biological samples by liquid chromatography-tandem mass spectrometry: Case report and analysis. Forensic Science and Technology. 2016; 41(5): 402–4. DOI: 10.16467/j.1008-3650.2016.05.014Zhang L., Han X., Du H., et al. Identifi cation of melatonin poisoning markers in biological samples by liquid chromatography-tandem mass spectrometry: Case report and analysis. Forensic Science and Technology. 2016; 41(5): 402–4. DOI: 10.16467/j.1008-3650.2016.05.014Allegra M., Gentile C., Tesoriere L., Livrea M.A. Protective effect of melatonin against cytotoxic actions of malondialdehyde: An in vitro study on human erythrocytes. J Pineal Res. 2002; 32(3): 187–93. DOI: 10.1034/j.1600-079x.2002.1o852.x.Allegra M., Gentile C., Tesoriere L., Livrea M.A. Protective effect of melatonin against cytotoxic actions of malondialdehyde: An in vitro study on human erythrocytes. J Pineal Res. 2002; 32(3): 187–93. DOI: 10.1034/j.1600-079x.2002.1o852.x.Antunes F., Barclay L.R., Ingold K.U., et al. on the antioxidant activity of melatonin. Free Radic Biol Med. 1999; 26(1-2): 117–28. DOI: 10.1016/s0891-5849(98)00168-3.Antunes F., Barclay L.R., Ingold K.U., et al. on the antioxidant activity of melatonin. Free Radic Biol Med. 1999; 26(1-2): 117–28. DOI: 10.1016/s0891-5849(98)00168-3.Wölfl er A., Caluba H.C., Abuja P.M., et al. Prooxidant activity of melatonin promotes fas-induced cell death in human leukemic Jurkat cells. FEBS Lett. 2001; 502(3): 127–31. DOI: 10.1016/s0014-5793(01)02680-1.Wölfl er A., Caluba H.C., Abuja P.M., et al. Prooxidant activity of melatonin promotes fas-induced cell death in human leukemic Jurkat cells. FEBS Lett. 2001; 502(3): 127–31. DOI: 10.1016/s0014-5793(01)02680-1.Albertini M.C., Radogna F., Accorsi A., et al. Intracellular pro-oxidant activity of melatonin deprives U937 cells of reduced glutathione without affecting glutathione peroxidase activity. Ann N Y Acad Sci. 2006; 1091: 10–6. DOI: 10.1196/annals.1378.050.Albertini M.C., Radogna F., Accorsi A., et al. Intracellular pro-oxidant activity of melatonin deprives U937 cells of reduced glutathione without affecting glutathione peroxidase activity. Ann N Y Acad Sci. 2006; 1091: 10–6. DOI: 10.1196/annals.1378.050.Cristofanon S., Uguccioni F., Cerella C., et al. Intracellular prooxidant activity of melatonin induces a survival pathway involving NF-kappa B activation. Ann N Y Acad Sci. 2009; 1171: 472–8. DOI: 10.1111/j.1749-6632.2009.04896.x.Cristofanon S., Uguccioni F., Cerella C., et al. Intracellular prooxidant activity of melatonin induces a survival pathway involving NF-kappa B activation. Ann N Y Acad Sci. 2009; 1171: 472–8. DOI: 10.1111/j.1749-6632.2009.04896.x.Ximenes V.F., Pessoa A.S., Padovan C.Z., et al. Oxidation of melatonin by AAPHderived peroxyl radicals: Evidence of a pro-oxidant effect of melatonin. Biochim Biophys Acta. 2009; 1790(8): 787–92. DOI: 10.1016/j.bbagen.2009.03.021.Ximenes V.F., Pessoa A.S., Padovan C.Z., et al. Oxidation of melatonin by AAPHderived peroxyl radicals: Evidence of a pro-oxidant effect of melatonin. Biochim Biophys Acta. 2009; 1790(8): 787–92. DOI: 10.1016/j.bbagen.2009.03.021.Poeggeler B., Saarela S., Reiter R.J., et al. Melatonin – a highly potent endogenous radical scavenger and electron donor: New aspects of the oxidation chemistry of this indole accessed in vitro. Ann N Y Acad Sci. 1994; 738: 419–20. DOI: 10.1111/j.1749-6632.1994.tb21831.x.Poeggeler B., Saarela S., Reiter R.J., et al. Melatonin – a highly potent endogenous radical scavenger and electron donor: New aspects of the oxidation chemistry of this indole accessed in vitro. Ann N Y Acad Sci. 1994; 738: 419–20. DOI: 10.1111/j.1749-6632.1994.tb21831.x.da Silva D.G., Ricci O. Jr, de Almeida E.A., Bonini-Domingos C.R. Potential utility of melatonin as an antioxidant therapy in the management of sickle cell anemia. J Pineal Res. 2014; 58(2): 178–88. DOI: 10.1111/jpi.12204.da Silva D.G., Ricci O. Jr, de Almeida E.A., Bonini-Domingos C.R. Potential utility of melatonin as an antioxidant therapy in the management of sickle cell anemia. J Pineal Res. 2014; 58(2): 178–88. DOI: 10.1111/jpi.12204.Tesoriere L., D’Arpa D., Conti S., et al. Melatonin protects human red blood cells from oxidative hemolysis: New insights into the radical-scavenging activity. J Pineal Res. 1999; 27(2): 95–105. DOI: 10.1111/j.1600-079x.1999.tb00602.x.Tesoriere L., D’Arpa D., Conti S., et al. Melatonin protects human red blood cells from oxidative hemolysis: New insights into the radical-scavenging activity. J Pineal Res. 1999; 27(2): 95–105. DOI: 10.1111/j.1600-079x.1999.tb00602.x.Mayo J.C., Tan D.X., Sainz R.M., et al. Protection against oxidative protein damage induced by metal-catalyzed reaction or alkylperoxyl radicals: Comparative effects of melatonin and other antioxidants. Biochim Biophys Acta. 2003; 1620(1-3): 139–50. DOI: 10.1016/s0304-4165(02)00527-5.Mayo J.C., Tan D.X., Sainz R.M., et al. Protection against oxidative protein damage induced by metal-catalyzed reaction or alkylperoxyl radicals: Comparative effects of melatonin and other antioxidants. Biochim Biophys Acta. 2003; 1620(1-3): 139–50. DOI: 10.1016/s0304-4165(02)00527-5.Sharma S., Singh H., Ahmad N., et al. The role of melatonin in diabetes: Therapeutic implications. Arch Endocrinol Metab. 2015; 59(5): 391–9. DOI: 10.1590/2359-3997000000098.Sharma S., Singh H., Ahmad N., et al. The role of melatonin in diabetes: Therapeutic implications. Arch Endocrinol Metab. 2015; 59(5): 391–9. DOI: 10.1590/2359-3997000000098.Karamitri A., Jockers R. Melatonin in type 2 diabetes mellitus and obesity. Nat Rev Endocrinol. 2019; 15(2): 105–25. DOI: 10.1038/s41574-018-0130-1.Karamitri A., Jockers R. Melatonin in type 2 diabetes mellitus and obesity. Nat Rev Endocrinol. 2019; 15(2): 105–25. DOI: 10.1038/s41574-018-0130-1.

The authors declare that there are no conflicts of interest present.