Oxidative stress (OS) is one of the major contributors to platelet storage lesions. Addition of antioxidant additives to storage solutions can mitigate oxidative damage to platelets. Caffeic acid (CA) is a polyphenolic compound that directly scavenges reactive oxygen species (ROS), inhibits lipid peroxidation, and modulates platelet function signaling pathways. This is the first study to investigate the influence of CA on stored platelets.
Methodology:
Platelets obtained from the blood of male Wistar rats (n = 5 per group) were resuspended in SSP+ combined with plasma at 70:30 ratio. ROS was analyzed during a 7-day storage period for different concentrations of CA. The concentration of CA that exhibited maximum inhibition was chosen for further studies. Platelets (n = 5) were divided into (1) controls and (2) CA and stored at 22°C under mild agitation for 11 days. The markers of platelet function, viability, OS, and antioxidant defenses were analyzed.
Results:
CA at 5 µM concentration (5-CA) showed maximum inhibition of ROS on day 7; hence, was chosen for further assays. 5-CA augmented antioxidant defenses, decreased lipid peroxidation, and scavenged superoxide radicals compared with controls. Decline in platelet activation, aggregation without collagen, and microbial contamination were also observed in 5-CA. Platelet viability and metabolism were maintained; lactate dehydrogenase decreased by the end of storage in 5-CA.
Conclusion:
5-CA in SSP+ could preserve the quality of stored platelets until day 7 of storage. This study emphasizes the potential of CA as an additive in platelet storage solutions in prolonging the shelf-life of platelets and maintaining their efficacy.
MittalK, KaurR. Platelet storage lesion: An update. Asian J Transfus Sci, 2015; 9(1):1–3; doi: 10.4103/0973-6247.150933
3.
LozanoM, EstebanellE, CidJ, et al.Platelet concentrates prepared and stored under currently optimal conditions: Minor impact on platelet adhesive and cohesive functions after storage. Transfus, 1999; 39(9):951–959; doi: 10.1046/j.1537-2995.1999.39090951.x
4.
HosseiniE, GhasemzadehM, AzizvakiliE, et al.Platelet spreading on fibrinogen matrix, a reliable and sensitive marker of platelet functional activity during storage. J Thromb Thrombolysis, 2019; 48(3):430–438; doi: 10.1007/s11239-019-01916-8
5.
van der MeerPF, de KorteD. Platelet additive solutions: A review of the latest developments and their clinical implications. Transfus Med Hemother, 2018; 45(2):98–102; doi: 10.1159/000487513
VillarroelJPP, FigueredoR, GuanY, et al.Increased platelet storage time is associated with mitochondrial dysfunction and impaired platelet function. J Surg Res, 2013; 184(1):422–429; doi: 10.1016/j.jss.2013.05.097
8.
HosseiniE, SoloukiA, RoudsariZO, et al.Reducing state attenuates ectodomain shedding of GPVI while restoring adhesion capacities of stored platelets: Evidence addressing the controversy around the effects of redox condition on thrombosis. J Thromb Thrombolysis, 2020; 50(1):123–134; doi: 10.1007/s11239-020-02137-0
9.
HornseyVS, McCollK, DrummondO, et al.Extended storage of platelets in SSP+ platelet additive solution. Vox Sang, 2006; 91(1):41–46; doi: 10.1111/j.1423-0410.2006.00771.x
10.
SaundersC, RoweG, WilkinsK, et al.In vitro storage characteristics of platelet concentrates suspended in 70% SSP+ TM additive solution versus plasma over a 14‐day storage period. Vox Sang, 2011; 101(2):112–121; doi: 10.1111/j.1423-0410.2011.01468.x
11.
RajanandMC, AnanthakrishnaAB, RajashekaraiahV. Oxidative modulations in platelets stored in SSP+, PAS-G and Tyrode’s buffer: A comparative analysis. Hematol Transfus Cell Ther, 2024; 46(Suppl 5):S80–S89; doi: 10.1016/j.htct.2024.04.121
HandigundM, BaeTW, LeeJ, et al.Evaluation of in vitro storage characteristics of cold stored platelet concentrates with N acetylcysteine (NAC). Transfus Apher Sci, 2016; 54(1):127–138; doi: 10.1016/j.transci.2016.01.006
14.
HosseiniE, GhasemzadehM, AtashibargM, et al.ROS scavenger, N‐acetyl‐l‐cysteine and NOX specific inhibitor, VAS2870 reduce platelets apoptosis while enhancing their viability during storage. Transfus, 2019; 59(4):1333–1343; doi: 10.1111/trf.15114
15.
HegdeS, WellendorfAM, ZhengY, et al.Antioxidant prevents clearance of hemostatically competent platelets after long‐term cold storage. Transfus, 2021; 61(2):557–567; doi: 10.1111/trf.16200
16.
MithunM, RajashekaraiahV. L-Carnitine as an additive in Tyrode’s buffer during platelet storage. Blood Coagul Fibrinolysis, 2018; 29(7):613–621; doi: 10.1097/MBC.0000000000000760
17.
AmiriF, DahajMM, SiasiNH, et al.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, 2021; 51(2):277–285; doi: 10.1007/s11239-020-02241-1
18.
EkaneyML, GrayGG, McKillopIH, et al.Enhanced platelet function in cold stored whole blood supplemented with resveratrol or cytochrome C. J Trauma Acute Care Surg, 2018; 85(1S Suppl 2):S92–S97; doi: 10.1097/TA.0000000000001887
19.
WangL, XieR, FanZ, et al.The contribution of oxidative stress to platelet senescence during storage. Transfus, 2019; 59(7):2389–2402; doi: 10.1111/trf.15291
20.
WangX, FanY, ShiR, et al.Quality assessment of platelets stored in a modified platelet additive solution with trehalose at low temperature (10 C) and in vivo effects on rabbit model of thrombocytopenia. Platelets, 2015; 26(1):72–79; doi: 10.3109/09537104.2013.872772
21.
ZhuangY, RenG, LiH, et al.In vitro properties of apheresis platelet during extended storage in plasma treated with anandamide. Transfus Apher Sci, 2014; 51(1):58–64; doi: 10.1016/j.transci.2014.03.009
22.
KhanFA, MaalikA, MurtazaG. Inhibitory mechanism against oxidative stress of caffeic acid. J Food Drug Anal, 2016; 24(4):695–702; doi: 10.1016/j.jfda.2016.05.003
TamerF, TullemansBM, KuijpersMJ, et al.Nutrition phytochemicals affecting platelet signaling and responsiveness: Implications for thrombosis and hemostasis. Thromb Haemost, 2022; 122(6):879–894; doi: 10.1055/a-1683-5599
25.
DeviSA, SubramanyamMVV, VaniR, et al.Adaptations of the antioxidant system in erythrocytes of trained adult rats: Impact of intermittent hypobaric-hypoxia at two altitudes. Comp Biochem Physiol C Toxicol Pharmacol, 2005; 140(1):59–67; doi: 10.1016/j.cca.2005.01.003
26.
CarneiroAMD, BlakelyRD. Serotonin-, protein kinase C-, and Hic-5-associated redistribution of the platelet serotonin transporter. J Biol Chem, 2006; 281(34):24769–24780; doi: 10.1074/jbc.M603877200
27.
BlasaM, AngelinoD, GennariL, et al.The cellular antioxidant activity in red blood cells (CAA-RBC): a new approach to bioavailability and synergy of phytochemicals and botanical extracts. Food Chem, 2011; 125(2):685–691; doi: 10.1016/j.foodchem.2010.09.065
28.
MisraHP, FridovichI. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem, 1972; 247(10):3170–3175; doi: 10.1016/S0021-9258(19)45228-9
29.
AebiH. Catalase in vitro. Methods Enzymol, 1984; 105:121–126.
30.
BeutlerE. Modified procedure for the estimation reduced glutathione. J Lab Clin Med, 1963; 61:882.
31.
Da CruzG. Use of bathocuproine for the evaluation of the antioxidant power in liquids and solutions. 2003;US patent 6613577.
32.
OlasB, WachowiczB. Resveratrol and vitamin C as antioxidants in blood platelets. Thromb Res, 2002; 106(2):143–148; doi: 10.1016/S0049-3848(02)00101-9
33.
ChenLY, MehtaP, MehtaJL. Oxidized LDL decreases L-arginine uptake and nitric oxide synthase protein expression in human platelets: Relevance of the effect of oxidized LDL on platelet function. Circulation, 1996; 93(9):1740–1746; doi: 10.1161/01.CIR.93.9.1740
34.
OlasB, NowakP, KolodziejczykJ, et al.Protective effects of resveratrol against oxidative/nitrative modifications of plasma proteins and lipids exposed to peroxynitrite. J Nutr Biochem, 2006; 17(2):96–102; doi: 10.1016/j.jnutbio.2005.05.010
35.
Witko-SarsatV, FriedlanderM, Capeillère-BlandinC, et al.Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int, 1996; 49(5):1304–1313; doi: 10.1038/ki.1996.186
36.
HabeebAFSA. Reaction of protein sulfhydryl groups with Ellman’s reagent. Methods Enzymol, 1972; 25:457–464; doi: 10.1016/S0076-6879(72)25041-8
37.
BornGVR, CrossMOJ. The aggregation of blood platelets. J Physiol, 1963; 168(1):178–195; doi: 10.1113/jphysiol.1963.sp007185
38.
WachowiczB, OlasB, ZbikowskaHM, et al.Generation of reactive oxygen species in blood platelets. Platelets, 2002; 13(3):175–182; doi: 10.1080/09533710022149395
39.
ShiriR, YariF, AhmadinejadM, et al.The caspase-3 inhibitor (peptide Z-DEVD-FMK) affects the survival and function of platelets in platelet concentrate during storage. Blood Res, 2014; 49(1):49–53; doi: 10.5045/br.2014.49.1.49
40.
SinghV, GoyalI, SainiA, et al.Studying the effect of Carica papaya leaf extract on the shelf life of platelets. Int J Sci Res, 2017; 6:2138–2146.
41.
LowryOH, RosebroughNJ, FarrAL, et al.Protein measurement with the Folin phenol reagent. J Biol Chem, 1951; 193(1):265–275.
42.
AmoriniAM, TuttobeneM, LazzarinoG, et al.Evaluation of biochemical parameters in platelet concentrates stored in glucose solution. Blood Transfus, 2007; 5(1):24–32; doi: 10.2450/2007.0019-06
43.
BasakA. Development of a rapid and inexpensive plasma glucose estimation by two-point kinetic method based on glucose oxidase-peroxidase enzymes. Indian J Clin Biochem, 2007; 22(1):156–160; doi: 10.1007/BF02912902
44.
BuhlSN, JacksonKY. Optimal conditions and comparison of lactate dehydrogenase catalysis of the lactate-to-pyruvate and pyruvate-to-lactate reactions in human serum at 25, 30, and 37 degrees C. Clin Chem, 1978; 24(5):828–831; doi: 10.1093/clinchem/24.5.828
45.
RajanandMC, AnanthakrishnaAB, RajashekaraiahV. A laboratory study on N-acetyl cysteine in SSP+ modulating oxidative stress and delaying the progression of storage lesion in platelets. Biomed Res Ther, 2024; 11(11):6950–6959; doi: 10.15419/bmrat.v11i11.941
46.
MauryaDK, DevasagayamTPA. Antioxidant and prooxidant nature of hydroxycinnamic acid derivatives ferulic and caffeic acids. Food Chem Toxicol, 2010; 48(12):3369–3373; doi: 10.1016/j.fct.2010.09.006
47.
HalliwellB. Free radicals and antioxidants: A personal view. Nutr Rev, 1994; 52(8 Pt 1):253–265; doi: 10.1111/j.1753-4887.1994.tb01453.x
48.
HalliwellB, GutteridgeJM. Free Radicals in Biology and Medicine. 5th edition. Oxford university press: New York; 2015.
49.
IrazM, OzerolE, GulecM, et al.Protective effect of caffeic acid phenethyl ester (CAPE) administration on cisplatin‐induced oxidative damage to liver in rat. Cell Biochem Funct, 2006; 24(4):357–361; doi: 10.1002/cbf.1232
50.
PengX, HuT, ZhangY, et al.Synthesis of caffeic acid sulfonamide derivatives and their protective effect against H2O2 induced oxidative damage in A549 cells. RSC Adv, 2020; 10(17):9924–9933; doi: 10.1039/D0RA00227E
51.
NimseSB, PalD. Free radicals, natural antioxidants, and their reaction mechanisms. RSC Adv, 2015; 5(35):27986–28006; doi: 10.1039/C4RA13315C
52.
YangSY, KangJH, SeomunY, et al.Caffeic acid induces glutathione synthesis through JNK/AP-1-mediated γ-glutamylcysteine ligase catalytic subunit induction in HepG2 and primary hepatocytes. Food Sci Biotechnol, 2015; 24(5):1845–1852; doi: 10.1007/s10068-015-0241-6
53.
ManasaM, VaniR. Evaluation of Caripill™ as a component of platelet storage solution. Hematol Transfus Cell Ther, 2021; 43(2):133–140; doi: 10.1016/j.htct.2020.01.003
WanYY, ZhangY, ZhangL, et al.Caffeic acid protects cucumber against chilling stress by regulating antioxidant enzyme activity and proline and soluble sugar contents. Acta Physiol Plant, 2015; 37(1):1–10; doi: 10.1007/s11738-014-1706-6
56.
AbdallahFB, FetouiH, FakhfakhF, et al.Caffeic acid and quercetin protect erythrocytes against the oxidative stress and the genotoxic effects of lambda-cyhalothrin in vitro. Hum Exp Toxicol, 2012; 31(1):92–100; doi: 10.1177/0960327111424303
57.
StarkeDW, ChenY, BapnaCP, et al.Sensitivity of protein sulfhydryl repair enzymes to oxidative stress. Free Radic Biol Med, 1997; 23(3):373–384; doi: 10.1016/S0891-5849(97)00009-9
58.
NaghadehHT, BadlouBA, FerizhandyAS, et al.Six hours of resting platelet concentrates stored at 22–24°C for 48 hours in permeable bags preserved pH, swirling and lactate dehydrogenase better and caused less platelet activation. Blood Transfus, 2013; 11(3):400–404; doi: 10.2450/2012.0035-12
59.
ZhaoX, ZhaoY, DingY, et al.Autophagy ameliorates reactive oxygen species‐induced platelet storage lesions. Oxid Med Cell Longev, 2022; 2022(1):1898844; doi: 10.1155/2022/1898844
60.
EhtiatiS, AlizadehM, FarhadiF, et al.Promising influences of caffeic acid and caffeic acid phenethyl ester against natural and chemical toxins: A comprehensive and mechanistic review. J Funct Foods, 2023; 107:105637; doi: 10.1016/j.jff.2023.105637
61.
JayanthiR, SubashP. Antioxidant effect of caffeic acid on oxytetracycline induced lipid peroxidation in albino rats. Indian J Clin Biochem, 2010; 25(4):371–375; doi: 10.1007/s12291-010-0052-8
62.
XuW, LuoQ, WenX, et al.Antioxidant and anti-diabetic effects of caffeic acid in a rat model of diabetes. Trop J Pharm Res, 2020; 19(6):1227–1232; doi: 10.4314/tjpr.v19i6.17
63.
SalauVF, ErukainureOL, IjomoneOM, et al.Caffeic acid regulates glucose homeostasis and inhibits purinergic and cholinergic activities while abating oxidative stress and dyslipidaemia in fructose-streptozotocin-induced diabetic rats. J Pharm Pharmacol, 2022; 74(7):973–984; doi: 10.1093/jpp/rgac021
64.
ChengJT, LiuIM. Stimulatory effect of caffeic acid on α 1A-adrenoceptors to increase glucose uptake into cultured C2C12 cells. Naunyn Schmiedebergs Arch Pharmacol, 2000; 362(2):122–127; doi: 10.1007/s002100000274
65.
HuangDW, ShenSC, WuJS. Effects of caffeic acid and cinnamic acid on glucose uptake in insulin-resistant mouse hepatocytes. J Agric Food Chem, 2009; 57(17):7687–7692; doi: 10.1021/jf901376x
66.
KhanF, BamunuarachchiNI, TabassumN, et al.Caffeic acid and its derivatives: Antimicrobial drugs toward microbial pathogens. J Agric Food Chem, 2021; 69(10):2979–3004; doi: 10.1021/acs.jafc.0c07579
