SPECT MPI (Single photon emission computed tomography myocardial perfusion imaging) is an essential tool for diagnosis of cardiovascular disease, but it also involves considerable exposure to ionizing radiation.
OBJECTIVE:
To determine the radioprotective potential of lipoic acid free and nano-capsule against 99mTc-MIBI-induced injury in cardiovascular tissue.
METHODS:
The radioprotective ability was assessed by blood count, histopathology and heart enzymes in different groups of mice. Hearts of mice from all groups were dissected and prepared for oxidative stress analysis of superoxide dismutase (SOD) and malondialdehyde (MDA). Furthermore, levels of DNA damage in heart and bone marrow cells were evaluated by alkaline comet assay technique. The same measurements were estimated after treating the mice with lipoic acid.
RESULTS:
Comparing mice injected by radiopharmaceutics with control group showed a significant depression in the count of white blood cells (WBC) by about 40 % at 24 &72 hrs post-radiopharmaceutical administration. Moreover, platelets count was decreased by 27% at 72 hrs post-radiopharmaceutical administration. Radiation also dropped in super oxide dismutase (SOD) and increased in activity of heart enzymes and level of MDA (Malondialdehyde). Additionally, histopathological observation was characterized by focal necrosis of cardiac myocytes. 99mTc-MIBI induced DNA damage had significant increase. Nevertheless, pretreatment with free and lipoic acid nano-capsules (LANC’s) prevented the reduction induced in WBCs and platelets, and improved their counts significantly. Conversely pre-treatment with lipoic acid free and nano-capsule significantly increased the activity of SOD and decreased the level of MDA and therefore protected the cardiovascular tissues and reduced DNA strand-break, consequently and enhanced the body weight of the mice.
CONCLUSIONS:
These findings highlight the efficacy of lipoic acid free and nano-capsule as a radio protector.
L.Shaw, T.M.Zoghbi, W.Hundley, et al., Why all the focus on cardiac imaging? JACC Cardiovasc Imaging3 (2010), 789–794.
2.
W.Hee Lee, P.Nguyen, S.Hu, et al., JosephVariable activation of the DNA Damage Response Pathways in Patients Undergoing SPECT Myocardial Perfusion Imaging, Circ Cardiovasc Imaging8(2) (2015), e002851. doi:10.1161/CIRCIMAGING.114.002851
3.
J.Chen, A.Einstein, R.Fazel, et al., Cumulative exposure to ionizing radiation from diagnostic and therapeutic cardiac imaging procedures: A population-based analysis, J Am Coll Cardiol56 (2010), 702–771.
4.
Y.Zhang, J.Guo, Y.Qi, et al., The prevention of radiation-induced DNA damage and apoptosis in human intestinal epithelial cells by salvianic acid A, Journal of Radiation Research and Applied Sciences7 (2014), 7274–7285.
5.
J.Weiss, Pharmacologic approaches to protection against radiation-induced lethality and other damage, Environmental Health Perspectives105 (1996), 1473–1478.
6.
M.Barcellos, C.Hoff and E.Park, Wright Radiation and the microenvironment—tumorigenesis and therapy, Nat Rev Cancer58 (2005), 867–875.
7.
V.Sonntag, the Chemical Basis of Radiation Biology, Taylor and Francis, London (1987).
8.
E.Hall, Radiobiology for the Radiologist. 2nd ed. Lippincott Williams & Williams, Philadelphia (2000).
9.
T.Ide, H.Tsutsui, S.Kinugawa, et al., Mitochondrial electron transport complex I is a potential source of oxygen free radicals in the failing myocardium, Circ Res85 (1999), 357–363.
10.
D.Siwik, J.Tzortzis, D.Pimental, et al., Inhibition of copper-zinc superoxide dismutase induces cell growth, hypertrophic phenotype, and apoptosis in neonatal rat cardiac myocytes in vitro, Circ Res85 (1999), 147–153.
11.
A.Dhalla, M.Hill and P.Singal, Role of oxidative stress in transition of hypertrophy to heart failure, J Am Coll Cardiol28 (1996), 506–514.
12.
K.Dixit, D.Bhatnagar, V.Kumar, et al., Antioxidant potential and radioprotective effect of soy isoflavone against gamma irradiation induced oxidative stress, Journal of Functional Foods4 (2012), 197–206.
13.
G.Jagetia, M.Baliga, K.Malagi and M.Kamath, The evaluation of radioprotective effect of Triphala (anayurvedic rejuvenating drug) in the mice exposed to gamma irradiation, Phytomedicine9 (2002), 99–108.
14.
S.Kumar, M.Unnikrishnan and P.Uma Devi, Effect of 5-aminosalicylic acid on radiation-induced micronuclei in mouse bone marrow, Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis527(1-2) (2003), 7–14.
15.
M.Lata, J.Prasad, S.Singh, et al., Whole body protection against lethal ionizing radiation in mice by REC-2001: A semi purified fraction of Podophyllum hexandrum, Phytomedicine16 (2009), 47–55.
16.
C.Krishanan and M.Garanett, Electrochemical Behavior of the super antioxidant, alfa lipoic acid, Int J Electrochem Sci6 (2011), 3607–3630.
17.
J.Teichert, T.Tuemmers, H.Achenbach, et al., Pharmacokinetics of lipoic acid in subjects with severe kidney damage and end-stage renal disease, J Clin Pharmacol45(3) (2005), 313–328.
18.
L.Packer, E.Witt and H.Tritschler, Lipoic acid as a biological antioxidant, Free Radic Biol Med19(2) (1995), 227–250.
19.
J.Davis, G.Dicky, J.Gunasingh Masilamoni, et al., Radioprotective effect of DL-a-lipoic acid on mice skin fibroblasts, Cell Biol Toxicol25 (2009), 331–340, DOI 10.1007/s10565-008-9087-5
20.
G.Biewenga, G.Haenen and A.Bast, The pharmacology of the antioxidant lipoic acid, Gen Pharmacol29(3) (1997), 315–331.
21.
J.Bustamante, J.Lodge, L.Marcocci, et al., Alpha lipoic acid in liver metabolism and disease, Free Radic Biol Med24 (1998), 1023–1039.
22.
V.Kagan, A.Shvedova, E.Serbinova, et al., Dihydrolipoic acid—a universal antioxidant both in the membrane and in the aqueous phase: Reduction of peroxyl, ascorbyl and chromanoxyl radicals, Biochem Pharmacol44 (1992), 1637–1649.
23.
M.Rahimifard, M.Navaei-Nigjeh, M.Baeeri, et al., Multiple protective mechanisms of alpha-lipoic acid in oxidation, apoptosis and inflammation against hydrogen peroxide induced toxicity in human lymphocytes, Mol Cell Biochem403 (2015), 179–186, DOI 10.1007/s11010-015-2348-8
24.
E.Miadokova, V.Vlckova and V.Duhova, Antimutagenic eVect of alpha-lipoic acid on three model test systems, Pharmazie55(11) (2000), 862–863.
25.
J.Teichert, R.Hermann, P.Ruus and R.Preiss, Plasma kinetics, metabolism, and urinary excretion of alpha-lipoic acid following oral administration in healthy volunteers, J Clin Pharmacol43(11) (2003), 1257–1267.
26.
R.C.Thomas and L.J.Reed, Disulfide Polymers of DL-a-Lipoic Acid, J Am Chem Soc78 (1956), 6148–6149.
27.
A.F.Wagner, E.Walton, G.E.Boxer, et al., Properties and Derivatives of α-Lipoic Acid, J Am Chem Soc78 (1956), 5079–5081.
28.
S.Matsugo, D.Han, H.Trischler and L.Packer, Decomposition of alpha-lipoic acid derivatives by photoirradiationformation of dihydrolipoic acid from alpha-lipoic acid, Biochem Mol Biol Int38 (1996), 51–59.
29.
V.Sridharan, J.W.Seawright, F.J.Antonawich, et al., Administration of a Palladium Lipoic Acid Complex (POLY-MVA) Modifies Cardiac Mitochondria but Not Functional or Structural Manifestations of Radiation-Induced Heart Disease in a Rat Model, Radiation research187 (2017), 361–366, 000-000, DOI:10.1667/RR14643.1
30.
A.Segall, M.Sosa, A.Alami, et al., Stability study of lipoic acid in the presence of vitamins A and E in o/w emulsions for cosmetic application, J Cosmet sci55 (2004), 449–461.
31.
E.B.Souto, R.H.Müller and S.Gohla, A novel approach based on lipid nanoparticles (SLN®) for topical delivery of a-lipoic acid, J Microencapsulation22 (2008), 581–592.
32.
M.G.Pecora, T.Musumeci, L.Musumeci, et al., Evaluation of Eudragit® Retard Polymers for the Microencapsulation of Alpha-Lipoic Acid, Current Drug Delivery13(7) (2016), 1165–1175.
33.
H.Nishiura, K.Sugimoto, K.Akiyama, et al., A Novel Nano-Capsule of α-Lipoic Acid as a Template of Core-Shell Structure Constructed by Self-Assembly, JNanomedNanotechol4 (2013), 155.
34.
Annals of the ICRP, Patient and Staff Radiological Protection in Cardiology, ICRP ref 4818-2733-7736, 2011.
35.
Institute for Laboratory Animal Research. Guide for the Care and Use of Laboratory Animals. National Academies Press, Washington, D. C (2011).
36.
S.Reitman and S.Frankel, A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases, Am J Clin Pathol28(1) (1957), 56–63.
N.P.Singh, M.McCoy, R.Tice and E.Schneider, A simple technique for quantitation of low levels of DNA damage in individual cells, Exp Cell Res175(1) (1988), 184–191.
39.
R.Tice, E.Agurell, D.Anderson, et al., Single cell gel/comet assay: Guidelines for in vitro and in vivo genetic toxicology testing, Environ Mol Mutagenesis35(3) (2000), 206–221.
40.
M.Rageh and R.El-Gebaly, Melanin nanoparticles: Antioxidant activities and effects on 7-ray-induced DNA damage in the mouse, Mutat Res Gen Tox En828 (2018), 15–22.
41.
G.Beller and D.Watson, Physiological basis of myocardial perfusion imaging with the technetium 99m agents, Semin NuclMed21(3) (1991), 173–181.
42.
R.El-Gebaly, I.Maamoun and N.Madian, Quantitative evaluation of the administrated dose affecting image quality in myocardial perfusion SPECT, Journal of X-Ray Science and Technology22 (2014), 529–537.
43.
R.El-Gebaly, M.Rageh and M.Adel, Evaluation of varying physical acquisition parameters in gamma camera gated cardiac SPECT, Journal of X-Ray Science and Technology23 (2015), 453–461.
44.
D.Maurya, S.Adhikari, C.Nair and T.Devasagayam, DNA protective properties of vanillin against gamma-radiation under different conditions: Possible mechanisms, Mutation Research634 (2007), 69–80.
45.
V.Benkovic, A.Knezevic and D.Dikic, et al., Radioprotective effects of quercetin and ethanolic extract of propolis in gamma irradiated mice, Arh Hig Rada Toksikol60 (2009), 129–138.
46.
B.Tiwari, V.Valdramidis, C.Donnel, et al., Application of natural antimicrobials for food preservation, Journal of Agricultural and Food Chemistry57 (2009), 5987–6000.
47.
W.Zhao, X.Jiang, W.Deng, et al., Antioxidant activities of Ganoderma lucidum polysaccharides and their role on DNA damage in mice induced by cobalt-60 gamma-irradiation" Food and Chemical Toxicology50 (2012), 303–309.
48.
N.Velauthapillai, J.Barfett, H.Jaffer, et al., Antioxidants taken orally prior to diagnostic radiation exposure can prevent DNA injury, J Vasc Interv Radiol28 (2017), 406–411.
49.
P.Goti, J.Savsani and P.B.Patel, Spectrophotometric method Development and validation for estimation of alfa lipoic acid in tablet dosage form"International Journal of Pharmacy and Pharmaceutical Sciences4 (2012), 5.
50.
G.Cesur, D.Ogut, M.Polat and K.Onge, Effects of 99mTc sestamibi on antioxidant defensesystem and lipid peroxidation in the heart of of Sprague Dawley rats, Toxicology and Industrial Health30(2) (2014), 154–159.
51.
E.Cicek, M.Yildiz, N.Delibas and S.Bahceli, The effects of thyroid scintigraphy studies on oxidative damage in patients, International Journal of Infectious Disease11(2007), 251–255.
52.
N.Gurbuz, F.Aydin, A.Boz, et al., The effects of 99mTechnetium-methylendiphosphonate and 99mTechnetium-methoxyisobutylisonitrile on erythrocyte antioxidant enzyme activities, Turkish Journal of Biochemistry35(2010), 163–182.
53.
H.Kaya, N.Delibas, M.Serteser, et al., The effect of melatonin on lipid peroxidation during radiotherapy in female rats, Strahlentherapie und Onkologie175 (1999), 285–288.
54.
H.Vincent, S.Powers, A.Dirks and P.Scarpace, Mechanism for obesity induced increase in myocardial lipid peroxidation, Int J Obes25 (2001), 378–378.
55.
T.Oury, B.Day and J.Crapo, Extracellular superoxide dismutase in vessels and airways of humans and baboons, Free Radical Biology and Medicine20 (1996), 957–965.
56.
A.Shirazi, E.Mihandoost, M.Mohseni, et al., Radio-protective effects of melatonin against irradiation-induced oxidative damage in rat peripheral blood, Physica Medica29 (2013), 65–74.
57.
M.Ghoneum, N.Badr EL-Din, S.Abdel Fattah and L.Tolentino, Arabinoxylan rice bran (MGN-3/Biobran) provides protection against whole-body 7-irradiation in mice via restoration of haematopoietic tissues, J Radiat Res54 (2013), 419.
58.
J.Zhao, Y.Mi, Y. Liu and S.Feng, Quantitative control of targeting effect of anticancer drugs formulated by ligand-conjugated nanoparticles of biodegradable copolymer blend Biomaterials33(6) (2012), 1948–58.
59.
A.Kunwar, B.Adhikary, S.Jayakumar, et al., Melanin, a promising radioprotector: Mechanisms of actions in a mice model, Toxicol Appl Pharmacol264 (2012), 202–211.
60.
M.Regeh, R.El-Gebaly, H.Abou-Shady, et al., Melanin Nanoparticles (MNPs) provide protection against whole-body -irradiation in mice via restoration of hematopoietic tissues, Mol Cell Biochem399 (2015), 59–69.
61.
F.Herodin, P.Bourin, J.Mayol, et al., Short-injection of antiapoptotic cytokine combinations soon after lethal γ-irradiation promotes survival, Blood101 (2003), 2609–2616.
62.
B.Lord and J.Hendry, Radiation toxicology: Bone marrow and leukemia. In:
LordJH (ed)Radiation toxicology: Bone marrow and leukemia. Taylor & Francis (1995), 1–21.
63.
E.Yazar, R.Col, K.Uney, et al., Effect of pentoxifylline on biochemical parameters in endotoxaemic New Zealand Withe rabbits, Bull Vet Inst Pulawy48 (2004), 297–299.
64.
A.Saenger and A.Jaffe, The use of biomarkers for the evaluation and treatment of patients with acute coronary syndromes, Med Clin North Am J91(4) (2007), 65781.
65.
N.Taunk, B.Haffty, J.Kostis and S.Goyal, Radiation-induced heart disease: Pathologic abnormalities and putative mechanisms, Front Oncol5 (2015), 39.
66.
H.Rodemann, Cellular basis of radiation-induced fibrosis, Radiotherapy and Oncology35(2) (1995), 83–90.
67.
J.Stewart and L.Fajardo, Radiation-induced heart disease: An update, Progress in Cardiovascular Diseases27(3) (1984), 173–19.
68.
J.Alwood, A.Kumar, L.Tran, et al., R.Globus Low dose, ionizing radiation and age-related changes in skeletal microarchitecture, J Aging Res (2012). 10.1155/2012/481983.
69.
N.G.Burnet, R.Wurm and J.H.Peacock, Low dose-rate fibroblast radiosensitivity and the prediction of patient response to radiotherapy, Int J Radiat Biol70 (1996), 289–300.
70.
N.M.Gandhi and C.K.Nair, Protection of DNA and membrane from gamma radiation induced damage by gallic acid, Molecular and Cellular Biochemistry278 (2005), 111–117.
71.
B.Gavrilov, I.Vezhenkova, D.Firsanov, et al., Slow elimination of phosphorylated histone gamma-H2AX from DNA of terminally differentiated mouse heart cells in situ, Biochem Biophys Res Commun347(4) (2006), 1048–1052.
72.
D.Firsanov, A.Vasilishina, A.Kropotov and V.Mikhailov, Dynamics of gammaH2AX formation and elimination in mammalian cells after X-irradiation, Biochimie94(11) (2012), 2416–2422.
73.
L.Ramachandran, C.V.Krishnan and C.K.Nair, Radioprotection by alpha-lipoic acid palladium complex formulation (POLY-MVA) in mice, Cancer Biother Radiopharm25(4) (2011), 395–399.
74.
F.Fucassi, J.Lowe, K.Pavey, et al., Alpha-Lipoic acid and glutathione protect against the prooxidant activity of SOD/catalase mimetic manganese salen derivatives, J Inorg Biochem101(2) (2006), 225–232.
