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. 2004;27(3):217–230. doi: 10.1385/MB:27:3:217

Therapeutic uses of antioxidant liposomes

William L Stone 1,✉, Milton Smith 2
PMCID: PMC7090671  PMID: 15247495

Abstract

This review will focus on the therapeutic uses of antioxidant liposomes. Antioxidant liposomes have a unique ability to deliver both lipid- and water-soluble antioxidants to tissues. This review will detail the varieties of antioxidants which have been incorporated into liposomes, their modes of administration, and the clinical conditions in which antioxidant liposomes could play an important therapeutic role. Antioxidant liposomes should be particularly useful for treating diseases or conditions in which oxidative stress plays a significant pathophysiological role because this technology has been shown to suppress oxidative stress. These diseases and conditions include cancer, trauma, irradiation, retinotherapy or prematurity, respiratory distress syndrome, chemical weapon exposure, and pulmonary infections.

Index Entries: Antioxidants, α-tocopherol, γ-tocopherol, liposomes, respiratory distress syndrome pulmonary infections

References

  • 1.Noguchi N., Watanabe A., Shi H. Diverse functions of antioxidants. Free Radic. Res. 2000;33:809–817. doi: 10.1080/10715760000301331. [DOI] [PubMed] [Google Scholar]
  • 2.Suntres Z. E. Role of antioxidants in paraquat toxicity. Toxicology. 2002;180:65–77. doi: 10.1016/s0300-483x(02)00382-7. [DOI] [PubMed] [Google Scholar]
  • 3.Evans C. Flavonoid antioxidants. Curr. Med. Chem. 2001;8:797–807. doi: 10.2174/0929867013373011. [DOI] [PubMed] [Google Scholar]
  • 4.Clarkson P. M., Thompson H. S. Antioxidants: what role do they play in physical activity and health? Am. J. Clin. Nutr. 2000;72:637S–646S. doi: 10.1093/ajcn/72.2.637S. [DOI] [PubMed] [Google Scholar]
  • 5.Gutteridge J. M., Halliwell B. Free radicals and antioxidants in the year 2000: a historical look to the future. Ann. NY Acad. Sci. 2000;899:136–147. doi: 10.1111/j.1749-6632.2000.tb06182.x. [DOI] [PubMed] [Google Scholar]
  • 6.Fang Y. Z., Yang S., Wu G. Free radicals, antioxidants, and nutrition. Nutrition (Burbank, Los Angeles Couny, Calif.) 2002;18:872–879. doi: 10.1016/s0899-9007(02)00916-4. [DOI] [PubMed] [Google Scholar]
  • 7.Brookes P. S., Levonen A. L., Shiva S., Sarti P., Darley-Usmar V. M. Mitochondria: regulators of signal transduction by reactive oxygen and nitrogen species. Free Radic. Biol. Med. 2002;33:755–764. doi: 10.1016/s0891-5849(02)00901-2. [DOI] [PubMed] [Google Scholar]
  • 8.Droge W. Free radicals in the physiological control of cell function. Physiol. Rev. 2002;82:47–95. doi: 10.1152/physrev.00018.2001. [DOI] [PubMed] [Google Scholar]
  • 9.McCord J. M. The evolution of free radicals and oxidative stress. Am. J. Med. 2000;108:652–659. doi: 10.1016/s0002-9343(00)00412-5. [DOI] [PubMed] [Google Scholar]
  • 10.Suntres Z., Shek P. Alleviation of paraquat-induced lung injury by pretreatment with bifunctional liposomes containing alpha-tocopherol and glutathione. Biochem. Pharmacol. 1996;52:1515–1520. doi: 10.1016/s0006-2952(96)89626-2. [DOI] [PubMed] [Google Scholar]
  • 11.Barclay L., Bailey A., Kong D. The antioxidant activity of alpha-tocopherol-bovine serum albumin complex in micellar and liposome autoxidations. J. Biol. Chem. 1985;260:15,809–15,814. [PubMed] [Google Scholar]
  • 12.Barclay L. The cooperative antioxidant role of glutathione with a lipid-soluble and a water-soluble antioxidant during peroxidation of liposomes initiated in the aqueous phase and in the lipid phase. J. Biol. Chem. 1988;263:16,138–16,142. [PubMed] [Google Scholar]
  • 13.Barclay L., Vinqvist M. Membrane peroxidation: inhibiting effects of water-soluble antioxidants on phospholipids of different charge types. Free Radic. Biol. Med. 1994;16:779–788. doi: 10.1016/0891-5849(94)90193-7. [DOI] [PubMed] [Google Scholar]
  • 14.Barclay L., Antunes F., Egawa Y., et al. The efficiency of antioxidants delivered by liposomal transfer. Biochim. Biophys. Acta. 1997;1328:1–12. doi: 10.1016/s0005-2736(97)00057-6. [DOI] [PubMed] [Google Scholar]
  • 15.Di Giulio A., Saletti A., Oratore A., Bozzi A. Monitoring by cis-parinaric fluorescence of free radical induced lipid peroxidation in aqueous liposome suspensions. J. Microencapsul. 1996;13:435–445. doi: 10.3109/02652049609026029. [DOI] [PubMed] [Google Scholar]
  • 16.Doba T., Burton G., Ingold K. Antioxidant and coantioxidant activity of vitamin C: the effect of vitamin C, either alone or in the presence of vitamin E or a water-soluble vitamin E analogue, upon the peroxidation of aqueous multilamellar phospholipid liposomes. Biochim. Biophys. Acta. 1985;835:298–303. doi: 10.1016/0005-2760(85)90285-1. [DOI] [PubMed] [Google Scholar]
  • 17.Hayashi K., Noguchi N., Niki E. Action of nitric oxide as an antioxidant against oxidation of soybean phosphatidylcholine liposomal membranes. FEBS Lett. 1995;370:37–40. doi: 10.1016/0014-5793(95)00786-9. [DOI] [PubMed] [Google Scholar]
  • 18.Koga T., Terao J. Antioxidant behaviors of vitamin E analogues in unilamellar vesicles. Biosci. Biotechnol. Biochem. 1996;60:1043–1045. doi: 10.1271/bbb.60.1043. [DOI] [PubMed] [Google Scholar]
  • 19.Takahashi M., Tsuchiya J., Niki E., Urano S. Action of vitamin E as antioxidant in phospholipid liposomal membranes as studied by spin label technique. J. Nutr. Sci. Vitaminol. (Tokyo) 1998;34:25–34. doi: 10.3177/jnsv.34.25. [DOI] [PubMed] [Google Scholar]
  • 20.Roberts W. C., Gordon M. H. Determination of the total antioxidant activity of fruits and vegetables by a liposome assay. J. Agric. Food Chem. 2003;51:1486–1493. doi: 10.1021/jf025983t. [DOI] [PubMed] [Google Scholar]
  • 21.Bittner O., Gal S., Pinchuk I., Danino D., Shinar H., Lichtenberg D. Copper-induced peroxidation of liposomal palmitoyllinoleoylphosphatidylcholine (PLPC), effect of antioxidants and its dependence on the oxidative stress. Chem. Phys. Lipids. 2002;114:81–98. doi: 10.1016/s0009-3084(01)00208-0. [DOI] [PubMed] [Google Scholar]
  • 22.Chow C.Y., Heath T. D. Rapid diffusion of the lipid phosphorus of phosphatidyl glycerol liposomes through polycarbonate membranes is caused by the oxidation of the unsaturated fatty acids. Biochim. Biophys. Acta. 1995;1239:168–176. doi: 10.1016/0005-2736(95)00167-2. [DOI] [PubMed] [Google Scholar]
  • 23.Gabrielska J., Sarapuk J., Przestalski S. Antioxidant protection of egg lecithin liposomes during sonication. Z. Naturforsch. [C] 1995;50:561–564. doi: 10.1515/znc-1995-7-814. [DOI] [PubMed] [Google Scholar]
  • 24.Papas A. M. Antioxidant Status, Diet, Nutrition and Health. Washington, DC: CRC Press; 1999. [Google Scholar]
  • 25.Kagan V., Bakalova R., Zhelev Z., et al. Intermembrane transfer and antioxidant action of alphatocopherol in liposomes. Arch. Biochem. Biophys. 1990;280:147–152. doi: 10.1016/0003-9861(90)90529-8. [DOI] [PubMed] [Google Scholar]
  • 26.Yamamoto Y., Komuro E., Niki E. Antioxidant activity of ubiquinol in solution and phosphatidyicholine liposome. J. Nutr. Sci. Vitaminol. (Tokyo) 1990;36:505–511. doi: 10.3177/jnsv.36.505. [DOI] [PubMed] [Google Scholar]
  • 27.Tesoriere L., Bongiorno A., Pintaudi A., DqAnna R., DqArpa D., Livrea M. Synergistic interactions between vitamin A and vitamin E against lipid peroxidation in phosphatidyicholine liposomes. Arch. Biochem. Biophys. 1996;326:57–63. doi: 10.1006/abbi.1996.0046. [DOI] [PubMed] [Google Scholar]
  • 28.Tesoriere L., Ciaccio M., Bongiorno A., Riccio A., Pintaudi A., Livrea M. Antioxidant activity of all-trans-retinol in homogeneous solution and in phosphatidyicholine liposomes. Arch. Biochem. Biophys. 1993;307:217–223. doi: 10.1006/abbi.1993.1581. [DOI] [PubMed] [Google Scholar]
  • 29.Tesoriere L., DqArpa D., Re R., Livrea M. Antioxidant reactions of all-trans retinol in phospholipid bilayers: effect of oxygen partial pressure, radical fluxes, and retinol concentration. Arch. Biochem. Biophys. 1997;343:13–18. doi: 10.1006/abbi.1997.0128. [DOI] [PubMed] [Google Scholar]
  • 30.Stahl W., Junghans A., de Boer B., Driomina E., Briviba K., Sies H. Carotenoid mixtures protect multilamellar liposomes against oxidative damage: synergistic effects of lycopene and lutein. FEBS Lett. 1998;427:305–308. doi: 10.1016/s0014-5793(98)00434-7. [DOI] [PubMed] [Google Scholar]
  • 31.Woodail A., Britton G., Jackson M. Antioxidant Antioxidant activity of carotenoids in phosphatidyicholine vesicles: chemical and structural considerations. Biochem. Soc. Trans. 1995;23:133S. doi: 10.1042/bst023133s. [DOI] [PubMed] [Google Scholar]
  • 32.Junghans A., Sies H., Stahl W. Carotenoid-containing unilamellar liposomes loaded with glutathione: a model to study hydrophobic-hydrophilic antioxidant interaction. Free Radic. Res. 2000;33:801–818. doi: 10.1080/10715760000301321. [DOI] [PubMed] [Google Scholar]
  • 33.Barros M. P., Pinto E., Colepicolo P., Pedersen M. Astaxanthin and peridinin inhibit oxidative damage in Fe(2+)-loaded liposomes: scavenging oxyradicals or changing membrane permeability? Biochem. Biophys. Res. Commun. 2001;288:225–232. doi: 10.1006/bbrc.2001.5765. [DOI] [PubMed] [Google Scholar]
  • 34.Saija A., Scalese M., Lanza M., Marzullo D., Bonina F., Castelli F. Flavonoids as antioxidant agents: importance of their interaction with biomembranes. Free Radic Biol. Med. 1995;19:481–486. doi: 10.1016/0891-5849(94)00240-k. [DOI] [PubMed] [Google Scholar]
  • 35.Arora A., Nair M. G., Strasburg G. M. Antioxidant activities of isoflavones and their biological metabolites in a liposomal system. Arch. Biochem. Biophys. 1998;356:133–141. doi: 10.1006/abbi.1998.0783. [DOI] [PubMed] [Google Scholar]
  • 36.Wiseman H., Laughton M., Arnstein H., Cannon M., Halliwell B. The antioxidant action of tamoxifen and its metabolites: inhibition of lipid peroxidation. FEBS Lett. 1990;263:192–194. doi: 10.1016/0014-5793(90)81371-t. [DOI] [PubMed] [Google Scholar]
  • 37.Wiseman H. Tamoxifen and estrogens as membrane antioxidants: comparison with cholesterol. Methods Enzymol. 1994;234:590–602. doi: 10.1016/0076-6879(94)34131-1. [DOI] [PubMed] [Google Scholar]
  • 38.Korytowski W., Zareba M., Girotti A. W. Nitric oxide inhibition of free radical-mediated cholesterol peroxidation in liposomal membranes. Biochemistry. 2000;39:6918–6928. doi: 10.1021/bi000393e. [DOI] [PubMed] [Google Scholar]
  • 39.Suzuki Y., Tsuchiya M., Wassail S., et al. Structural and dynamic membrane properties of alpha-tocopherol and alpha-tocotrienol: implication to the molecular mechanism of their antioxidant potency. Biochemistry. 1993;32:10,692–10,699. doi: 10.1021/bi00091a020. [DOI] [PubMed] [Google Scholar]
  • 40.Liebler D., Stratton S., Kaysen K. Antioxidant actions of beta-carotene in liposomal and microsomal membranes: role of carotenoid-membrane incorporation and alpha-tocopherol. Arch. Biochem. Biophys. 1997;338:244–250. doi: 10.1006/abbi.1996.9822. [DOI] [PubMed] [Google Scholar]
  • 41.Chen G., Djuric Z. Carotenoids are degraded by free radicals but do not affect lipid peroxidation in unilamellar liposomes under different oxygen tensions. FEBS Lett. 2001;505:151–154. doi: 10.1016/s0014-5793(01)02671-0. [DOI] [PubMed] [Google Scholar]
  • 42.Stratton S. P., Liebler D. C. Determination of singlet oxygen-specific versus radical-mediated lipid peroxidation in photosensitized oxidation of lipid bilayers: effect of beta-carotene and alphatocopherol. Biochemistry. 1997;36:12,911–12,920. doi: 10.1021/bi9708646. [DOI] [PubMed] [Google Scholar]
  • 43.Potapenko A. Y., Kyagova A. A. The application of antioxidants in investigations and optimization of photochemotherapy. Membr. Cell Biol. 1998;12:269–278. [PubMed] [Google Scholar]
  • 44.Engelmann B., Brutigam C., Thiery J. Plasmalogen phospholipids as potential protectors against lipid peroxidation of 10 density lipoproteins. Biochem. Biophys. Res. Commun. 1994;204:1235–1242. doi: 10.1006/bbrc.1994.2595. [DOI] [PubMed] [Google Scholar]
  • 45.Vance J. E. Lipoproteins secreted by cultured rat hepatocytes contain the antioxidant 1-aIk-1-eny1-2-acylglycerophosphoethanolamine. Biochim. Biophys. Acta. 1990;1045:128–134. doi: 10.1016/0005-2760(90)90141-j. [DOI] [PubMed] [Google Scholar]
  • 46.Zommara M., Tachibana N., Mitsui K., et al. Inhibitory effect of ethanolamine plasmalogen on iron- and copper-dependent lipid peroxidation. Free Radic. Biol. Med. 1995;18:599–602. doi: 10.1016/0891-5849(94)00155-d. [DOI] [PubMed] [Google Scholar]
  • 47.Sindelar P. J., Guan Z., Dallner G., Ernster L. The protective role of plasmalogens in iron-induced lipid peroxidation. Free Radic. Biol. Med. 1999;26:318–324. doi: 10.1016/s0891-5849(98)00221-4. [DOI] [PubMed] [Google Scholar]
  • 48.Koga T., Nagao A., Terao J., Sawada K., Mukai K. Synthesis of a phosphatidyl derivative of vitamin E and its antioxidant activity in phospholipid bilayers. Lipids. 1994;29:83–89. doi: 10.1007/BF02537147. [DOI] [PubMed] [Google Scholar]
  • 49.Thomas C., McLean L., Parker R., Ohlweiler D. Ascorbate and phenolic antioxidant interactions in prevention of liposomal oxidation. Lipids. 1992;27:543–550. doi: 10.1007/BF02536138. [DOI] [PubMed] [Google Scholar]
  • 50.Kagan V., Shvedova A., Serbinova E., et al. Dihydrolipoic acid—a universal antioxidant both in the membrane and in the aqueous phase: reduction of peroxyl, ascorhyl and chromanoxyl radicals. Biochem. Pharmacol. 1992;44:1637–1649. doi: 10.1016/0006-2952(92)90482-x. [DOI] [PubMed] [Google Scholar]
  • 51.Ma V. S., Stone W. L., LeClair I. O. The effects of vitamin C and urate on the oxidation kinetics of human low-density lipoprotein. Proc. Soc. Exp. Biol. Med. 1994;206:53–59. doi: 10.3181/00379727-206-43722. [DOI] [PubMed] [Google Scholar]
  • 52.Mikami T., Yoshino Y., Ro A. Does a relationship exist between the urate pool in the body and lipid peroxidation during exercise? Free Radic. Res. 2000;32:31–39. doi: 10.1080/10715760000300041. [DOI] [PubMed] [Google Scholar]
  • 53.Rosefl M., Regnstrom J., Kaitner A., Hellenius M. L. Serum urate determines antioxidant capacity in middle-aged men—a controlled, randomized diet and exercise intervention study. J. Intern. Med. 1999;246:219–226. doi: 10.1046/j.1365-2796.1999.00522.x. [DOI] [PubMed] [Google Scholar]
  • 54.Turrens J. The potential of antioxidant enzymes as pharmacological agents in vivo. Xenobiotica. 1991;21:1033–1040. doi: 10.3109/00498259109039543. [DOI] [PubMed] [Google Scholar]
  • 55.White C., Jackson J., Abuchowski A., et al. Polyethylene glycol-attached antioxidant enzymes decrease pulmonary oxygen toxicity in rats. J Appl. Physiol. 1989;66:584–590. doi: 10.1152/jappl.1989.66.2.584. [DOI] [PubMed] [Google Scholar]
  • 56.Aoki H., Fujita M., Sun C., Fuji K., Mivajima K. High-efficiency entrapment of superoxide dismutase into cationic liposomes containing synthetic arninoglycolipid. Chem. Pharm. Bull. (Tokyo) 1997;45:1327–1331. doi: 10.1248/cpb.45.1327. [DOI] [PubMed] [Google Scholar]
  • 57.Miyajima K., Komatsu H., Sun C., et al. Effects of cholesterol on the miscibility of synthetic glucosamine diesters in lipid bilayers and the entrapment of superoxide dismutase into the positively charged liposomes. Chem. Pharm. Bull. (Tokyo) 1993;41:1889–1894. doi: 10.1248/cpb.41.1889. [DOI] [PubMed] [Google Scholar]
  • 58.Freeman B. A., Young S. L., Crapo J. D. Liposome-mediated augmentation of superoxide dismutase in endothelial cells prevents oxygen injury. J. Biol. Chem. 1983;258:12,534–12,542. [PubMed] [Google Scholar]
  • 59.Beckman J. S., Minor R. L., Freeman B. A. Augmentation of antioxidant enzymes in vascular endothelium. J. Free Radic. Biol. Med. 1986;2:359–365. doi: 10.1016/s0748-5514(86)80036-8. [DOI] [PubMed] [Google Scholar]
  • 60.Natsuki R., Morita Y., Osawa S., Takeda Y. Effects of liposome size on penetration of dltocopherol acetate into skin. Biol. Pharm. Bull. 1996;19:758–761. doi: 10.1248/bpb.19.758. [DOI] [PubMed] [Google Scholar]
  • 61.Christen S., Woodall A., Shigenaga M., Southwell-Keely P., Duncan M., Ames B. Gammatocopherol traps mutagenic electrophiles such as NO(X) and complements alpha-tocopherol: physiological implications. Proc. Natl. Acad. Sci. USA. 1997;94:3217–3222. doi: 10.1073/pnas.94.7.3217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 62.Nakamura T., Goto M., Matsumoto A., Tanaka I. Inhibition of NF-kappa B transcriptional activity by alpha-tocopheryl succinate. Biofactors. 1998;7:21–30. doi: 10.1002/biof.5520070104. [DOI] [PubMed] [Google Scholar]
  • 63.Yao T., Degli Esposti S., Huang L., et al. Inhibition of carbon tetrachloride-induced liver injury by liposomes containing vitamin E. Am. J. Physiol. 1994;267:C476–C484. doi: 10.1152/ajpgi.1994.267.3.G476. [DOI] [PubMed] [Google Scholar]
  • 64.Imaizumi S., Woolworth V., Khiouchi H., Chen S. F., Fishman R. A., Chan P. H. Liposome-entrapped superoxide dismutase ameliorates infarct volume in focal cerebral ischaemia. Acta Neurochir. Suppl. (Wien) 1990;51:236–238. doi: 10.1007/978-3-7091-9115-6_79. [DOI] [PubMed] [Google Scholar]
  • 65.Imaizumi S., Woolworth V., Fishman R. A., Chan P. H. Liposome-entrapped superoxide dismutase reduces cerebral infarction in cerebral isehemia in rats. Stroke. 1990;21:1312–1317. doi: 10.1161/01.str.21.9.1312. [DOI] [PubMed] [Google Scholar]
  • 66.Lamproglou I., Magdeienat H., Boisserie G., et al. An experimental model of acute encephalopathy after total body irradiation in the rat: effect of liposome-entrapped Cu/Zn superoxide dismutase. Int. J. Radiat. Oncol. Biol. Phys. 1998;42:179–184. doi: 10.1016/s0360-3016(98)00202-8. [DOI] [PubMed] [Google Scholar]
  • 67.Stanimirovic D. B., Markovic M., Micic D. V., Spatz M., Mrsulja B. B. Liposome-entrapped superoxide dismutase reduces ischemia/reperfusion “oxidative stress” in gerbil brain. Neurochem. Res. 1994;19:1473–1478. doi: 10.1007/BF00968993. [DOI] [PubMed] [Google Scholar]
  • 68.SlepGSHkin V. A., Simes S., Dazin P., et al. Sterically stabilized pH-sensitive liposomes: intracellular delivery of aqueous contents and prolonged circulation in vivo. J. Biol. Chem. 1997;272:2382–2388. doi: 10.1074/jbc.272.4.2382. [DOI] [PubMed] [Google Scholar]
  • 69.Corvo M. L., Boerman O. C., Oyen W. J., et al. Subcutaneous administration of superoxide dismutase entrapped in long circulating liposomes: in vivo fate and therapeutic activity in an inflammation model. Pharm. Res. 2000;17:600–606. doi: 10.1023/a:1007577101964. [DOI] [PubMed] [Google Scholar]
  • 70.Corvo M. L., Boerman O. C., Oyen W. J., et al. Intravenous administration of superoxide dismutase entrapped in long circulating liposomes. II. In vivo fate in a rat model of adjuvant arthritis. Biochim. Biophys. Acta. 1999;1419:325–334. doi: 10.1016/s0005-2736(99)00081-4. [DOI] [PubMed] [Google Scholar]
  • 71.Gaspar M. M., Martins M. B., Corvo M. L., Cruz M. E. Design and characterization of enzymosomes with surface-exposed superoxide dismutase. Biochim. Biophys. Acta. 2003;1609:211–217. doi: 10.1016/s0005-2736(02)00702-2. [DOI] [PubMed] [Google Scholar]
  • 72.Galovi-Rengel R., Barisi K., Paveli Z., Zani-Grubisi T., Cepelak I., Filipovi-Grci J. High efficiency entrapment of superoxide dismutase into mucoadhesive chitosan-coated liposomes. Eur. J. Pharm. Sci. 2002;15:441–448. doi: 10.1016/s0928-0987(02)00030-1. [DOI] [PubMed] [Google Scholar]
  • 73.Tang C. S., Su J. Y., Li Z. P., et al. Possibility of targeting treatment for ischemic heart disease with liposome (II) Sci. China B. 1993;36:809–816. [PubMed] [Google Scholar]
  • 74.Demopoulos H., Pietronigro D., Flamm E., Seligman M. The possible role of free radical reactions in carcinogenesis. J. Environ. Pathol. Toxicol. 1980;3:273–303. [PubMed] [Google Scholar]
  • 75.Stone W. L., Papas A. M. Tocopherols and the etiology of colon cancer. J. Natl. Cancer Inst. 1997;89:1006–1014. doi: 10.1093/jnci/89.14.1006. [DOI] [PubMed] [Google Scholar]
  • 76.Schwartz J., Shklar G., Flynn E., Trickler D. The administration of beta carotene to prevent and regress oral carcinoma in the hamster cheek pouch and the associated enhancement of the immune response. Adv. Exp. Med. Biol. 1990;262:77–93. doi: 10.1007/978-1-4613-0553-8_7. [DOI] [PubMed] [Google Scholar]
  • 77.Lippman S. M., Kessler J. F., Meyskens F. L. J. Retinoids as preventive and therapeutic anticancer agents (Part II) Cancer Treat. Rep. 1987;71:493–515. [PubMed] [Google Scholar]
  • 78.Smith M. A., Parkinson D. R., Cheson B. D., Friedman M. A. Retinoids in cancer therapy. J. Clin. Oncol. 1992;10:839–864. doi: 10.1200/JCO.1992.10.5.839. [DOI] [PubMed] [Google Scholar]
  • 79.Chomienne C., Ballerini P., Balitrand N., et al. The retinoic acid receptor alpha gene is rearranged in retinoic acid-sensitive promyelocytic leukemias. Leukemia. 1990;4:802–807. [PubMed] [Google Scholar]
  • 80.Castaigne S., Chomienne C., Daniel M. T., et al. Retinoic acids in the treatment of acute promyelocytic leukemia. Nouv. Rev. Fr. Hematol. 1990;32:36–38. [PubMed] [Google Scholar]
  • 81.Chomienne C., Ballerini P., Balitrand N., et al. All-trans retinoic acid in acute promyelocytic leukemias. II. in vitro studies: structure-function relationship. Blood. 1990;76:1710–1717. [PubMed] [Google Scholar]
  • 82.Sacks P. G., Oke V., Mehta K. Antiproliferative effects of free and liposome-encapsulated retinoic acid in a squamous carcinoma model: monolayer cells and multicellular tumor spheroids. J. Cancer Res. Clin. Oncol. 1992;118:490–496. doi: 10.1007/BF01225262. [DOI] [PubMed] [Google Scholar]
  • 83.Parthasarathy R., Sacks P. G., Harris D., Brock H., Mehta K. Interaction of liposome-associated all-trans-retinoic acid with squamous carcinoma cells. Cancer Chemother. Pharmacol. 1994;34:527–534. doi: 10.1007/BF00685666. [DOI] [PubMed] [Google Scholar]
  • 84.Fiorentini D., Cabini L., Landi L. Ubiquinol-3 and ubiquinol-7 exhibit similar antioxidant activity in model membranes. Free Radic. Res. Commun. 1993;18:201–209. doi: 10.3109/10715769309145869. [DOI] [PubMed] [Google Scholar]
  • 85.Bilenko M., Morgunov A., Churakova T., Bulgakov V., Komarov P. Disorders of cardiac contractile function in ischemic shock: the protective effect of antioxidants and liposomes made from egg phospholipids. Biull. Eksp. Biol. Med. 1989;108:660–663. [PubMed] [Google Scholar]
  • 86.Ferrari R., Agnoletti L., Comini L., et al. Oxidative stress during myocardial ischaemia and heart failure. Eur. Heart J. 1998;19(Suppl B):B2–B11. [PubMed] [Google Scholar]
  • 87.Janero D., Burghardt B. Oxidative injury to myocardial membrane: direct modulation by endogenous alpha-tocopherol. J. Mol. Cell Cardiol. 1989;21:1111–1124. doi: 10.1016/0022-2828(89)90689-5. [DOI] [PubMed] [Google Scholar]
  • 88.Sjogren K., Hjalmarson A., Ek B. Antioxidants protect against reoxygenation-induced cell damage in ventricular myocytes. Biochem. Soc. Trans. 1992;20:233S. doi: 10.1042/bst020233s. [DOI] [PubMed] [Google Scholar]
  • 89.Gupta A., Majumdar S., Sanyal S. Effect of lung surfactant liposomes on the rabbit fetal lung type 11 cell antioxidant enzymes following prenatal dexamethasone treatment. Res. Exp. Med. (Berl.) 1996;196:67–76. doi: 10.1007/BF02576829. [DOI] [PubMed] [Google Scholar]
  • 90.Oldham K. M., Bowen P. E. Oxidative stress in critical care: is antioxidant supplementation beneficial? J. Am. Diet. Assoc. 1998;98:1001–1008. doi: 10.1016/S0002-8223(98)00230-2. [DOI] [PubMed] [Google Scholar]
  • 91.Das D. K., Russell J. C., Jones R. M. Reduction of cold injury by superoxide dismutase and catalase. Free Radic. Res. Commun. 1991;12–13:653–662. doi: 10.3109/10715769109145843. [DOI] [PubMed] [Google Scholar]
  • 92.Chan P. H., Longar S., Fishman R. A. Protective effects of liposome-entrapped superoxide dismutase on posttraumatic brain edema. Ann. Neurol. 1987;21:540–547. doi: 10.1002/ana.410210604. [DOI] [PubMed] [Google Scholar]
  • 93.Chan P. H. Antioxidant-dependent amelioration of brain injury: role of CuZn-superoxide dismutase. J. Neurotrauma. 1992;9(Suppl 2):417–423. [PubMed] [Google Scholar]
  • 94.Michelson A. M., Jadot G., Puget K. Treatment of brain trauma with liposomal superoxide dismutase. Free Radic. Res. Commun. 1988;4:209–224. doi: 10.3109/10715768809055145. [DOI] [PubMed] [Google Scholar]
  • 95.Papp A., Nemeth I., Pelle Z., Tekulics P. Prospective biochemical study of the antioxidant defense capacity in retinopathy of prematurity. Orv. Hetil. 1997;138:201–205. [PubMed] [Google Scholar]
  • 96.Papp A., Nemeth I., Karg E., Papp E. Glutathione status in retinopathy of prematurity. Free Radic. Biol. Med. 1999;27:738–743. doi: 10.1016/s0891-5849(99)00041-6. [DOI] [PubMed] [Google Scholar]
  • 97.Hardy P., Dumont I., Bhattacharya M., et al. Oxidants, nitric oxide and prostanoids in the developing ocular vasculature: a basis for ischemic retinopathy. Cardiovasc. Res. 2000;47:489–509. doi: 10.1016/s0008-6363(00)00084-5. [DOI] [PubMed] [Google Scholar]
  • 98.Niesman M., Johnson K., Penn J. Therapeutic effect of liposomal superoxide dismutase in an animal model of retinopathy of prematurity. Neurochem. Res. 1997;22:597–605. doi: 10.1023/a:1022474120512. [DOI] [PubMed] [Google Scholar]
  • 99.Stone W. L. Oxidative stress and antioxidants in premature infants. In: Papas A. M., editor. Antioxidant Status, Diet, Nutrition, and Health. Washington, DC: CRC Press; 1999. pp. 277–297. [Google Scholar]
  • 100.Bernard G. R. N-acetylcysteine in experimental and clinical acute lung injury. Am. J. Med. 1991;91:54S–59S. doi: 10.1016/0002-9343(91)90284-5. [DOI] [PubMed] [Google Scholar]
  • 101.Bernard G. R., Wheeler A. P., Arons M. M., et al. A trial of antioxidants N-acetyleystcine and procysteine in ARDS: the Antioxidant in ARDS Study Group. Chest. 1997;112:164–172. doi: 10.1378/chest.112.1.164. [DOI] [PubMed] [Google Scholar]
  • 102.Shek P., Suntres Z., Brooks J. Liposomes in pulmonary applications: physicochemical considerations, pulmonary distribution and antioxidant delivery. J. Drug Target. 1994;2:431–442. doi: 10.3109/10611869408996819. [DOI] [PubMed] [Google Scholar]
  • 103.Smith L., Anderson J. Lung retention of phosphatidylcholine and cholesterol from liposomes: effects of oxygen exposure and fasting. J. Appl. Physiol. 1993;74:1899–1904. doi: 10.1152/jappl.1993.74.4.1899. [DOI] [PubMed] [Google Scholar]
  • 104.Baker R. R., Czopf L., Jilling T., Freeman B. A., Kirk K. L., Matalon S. Quantitation of alveolar distribution of liposome-entrapped antioxidant enzymes. Am. J. Physiol. 1992;263:585–594. doi: 10.1152/ajplung.1992.263.5.L585. [DOI] [PubMed] [Google Scholar]
  • 105.Walther F. J., David-Cu R., Lopez S. L. Antioxidant-surfactant liposomes mitigate hyperoxic lung injury in premature rabbits. Am. J. Physiol. 1995;269:613–617. doi: 10.1152/ajplung.1995.269.5.L613. [DOI] [PubMed] [Google Scholar]
  • 106.Walther F., Mehta E., Padbury J. Lung CuZn-superoxide dismutase and catalase gene expression in premature rabbits treated intratracheally with antioxidant-surfactant liposomes. Biochem. Mol. Med. 1996;59:169–173. doi: 10.1006/bmme.1996.0083. [DOI] [PubMed] [Google Scholar]
  • 107.Archer S. L., Peterson D., Nelson D. P., et al. Oxygen radicals and antioxidant enzymes alter pulmonary vascular reactivity in the rat lung. J. Appl. Physiol. 1989;66:102–111. doi: 10.1152/jappl.1989.66.1.102. [DOI] [PubMed] [Google Scholar]
  • 108.Freeman B. A., Turrens J. F., Mirza Z., Crapo J. D., Young S. L. Modulation of oxidant lung injury by using liposome-entrapped superoxide dismutase and catalase. Fed. Proc. 1985;44:2591–2595. [PubMed] [Google Scholar]
  • 109.Padmanabhan R. V., Gudapaty R., Liener I. E., Schwartz B. A., Hoidal J. R. Protection against pulmonary oxygen toxicity in rats by the intratracheal administration of liposome-encapsulated superoxide dismutase or catalse. Am. Rev. Respir. Dis. 1985;132:164–167. doi: 10.1164/arrd.1985.132.1.164. [DOI] [PubMed] [Google Scholar]
  • 110.Barnard M. L., Baker R. R., Matalon S. Mitigation of oxidant injury to lung microvasculature by intratracheal instillation of antioxidant enzymes. Am. J. Physiol. 1993;265:L340–L345. doi: 10.1152/ajplung.1993.265.4.L340. [DOI] [PubMed] [Google Scholar]
  • 111.Tanswell A. K., Freeman B. A. Liposome-entrapped antioxidant enzymes prevent lethal O2 toxicity in the newborn rat. J. Appl. Physiol. 1987;63:347–352. doi: 10.1152/jappl.1987.63.1.347. [DOI] [PubMed] [Google Scholar]
  • 112.Tanswell A. K., Olson D. M., Freeman B. A. Liposome-mediated augmentation of antioxidant defenses in fetal rat pneumocytes. Am. J. Physiol. 1990;258:L165–L172. doi: 10.1152/ajplung.1990.258.4.L165. [DOI] [PubMed] [Google Scholar]
  • 113.Tanswell A. K., Olson D. M., Freeman B. A. Response of fetal rat lung fibrobasts to elevated oxygen concentrations after liposome-mediated augmentation of antioxidant enzymes. Biochim. Biophys. Acta. 1990;1044:269–274. doi: 10.1016/0005-2760(90)90313-m. [DOI] [PubMed] [Google Scholar]
  • 114.Briscoe P., Caniggia I., Craves A., et al. Delivery of superoxide dismutase to pulmonary epithelium via p11-sensitive liposomes. Am. J. Physiol. 1995;268:374–380. doi: 10.1152/ajplung.1995.268.3.L374. [DOI] [PubMed] [Google Scholar]
  • 115.Walther F., David-Cu R., Supnet M., Longo M., Fan B., Bruni R. Uptake of antioxidants in surfactant liposomes by cultured alveolar type U cells is enhanced by SP-A. Am. J. Physiol. 1993;265:L330–L339. doi: 10.1152/ajplung.1993.265.4.L330. [DOI] [PubMed] [Google Scholar]
  • 116.Suntres Z., Shek P. Prevention of phorbol myristate acetate-induced acute lung injury by alphatocopherol liposomes. J. Drug Target. 1995;3:201–208. doi: 10.3109/10611869509015946. [DOI] [PubMed] [Google Scholar]
  • 117.Thibeault D., Rezaiekhaligh M., Mabry S., Beringer T. Prevention of chronic pulmonary oxygen toxicity in young rats with liposome-encapsulated catalase administered intratracheally. Pediatr. Pulmonol. 1991;11:318–327. doi: 10.1002/ppul.1950110408. [DOI] [PubMed] [Google Scholar]
  • 118.Ledwozyw A. Protective effect of liposome-entrapped superoxide dismutase and catalase on bleomycin-induced lung injury in rats. I. antioxidant enzyme activities and lipid peroxidation. Acta Vet. Hung. 1991;39:215–224. [PubMed] [Google Scholar]
  • 119.Muzykantov V. R. Targeting of superoxide dismutase and catalase to vascular endothelium. J. Control Release. 2001;71:1–21. doi: 10.1016/s0168-3659(01)00215-2. [DOI] [PubMed] [Google Scholar]
  • 120.Muzykantov V. R. Delivery of antioxidant enzyme proteins to the lung. Antioxid. Redox. Signal. 2001;3:39–62. doi: 10.1089/152308601750100489. [DOI] [PubMed] [Google Scholar]
  • 121.Suntres Z. E., Shek P. N. Prophylaxis against Iipopolysaccharide-induced acute lung injury by alpha-tocopherol liposomes. Crit. Care. Med. 1998;26:723–729. doi: 10.1097/00003246-199804000-00023. [DOI] [PubMed] [Google Scholar]
  • 122.Suntres Z. E., Shek P. N. Prophylaxis against lipopolysaccharide-induced lung injuries by liposome-entrapped dexamethasone in rats. Biochem. Pharmacol. 2000;59:1155–1161. doi: 10.1016/s0006-2952(99)00411-6. [DOI] [PubMed] [Google Scholar]
  • 123.Chetverikova L. K., Inozemtseva L. I. Role of lipid peroxidation in the pathogenesis of influenza and search for antiviral protective agents (Translated from Russian) Vestn. Ross. Akad. Med. Nauk. 1996;26:37–40. [PubMed] [Google Scholar]
  • 124.Gorbunov N. V., Volgarev A. P., Brailovskaia I. V., Bykova N. O., Avrova N. F., Kiselev O. I. Activation of free radicals reaction and changes in the state of antioxidant protection in blood in toxic experimental influenza infection (Translated from Russian) Biull. Eksp. Biol. Med. 1992;114:42–44. [PubMed] [Google Scholar]
  • 125.Nagibina M. V., Neifakh E. A., Krylov V. F., Braginskii D. M., Kulagina M. G. The treatment of pneumonias in influenza using antioxidants (Translated from Russian) Ter. Arkh. 1996;68:33–35. [PubMed] [Google Scholar]
  • 126.Christen S., Peterhans E., Stocker R. Antioxidant activities of some tryptophan metabolites: possible implication for inflammatory diseases. Proc. Natl. Acad. Sci. USA. 1990;87:2506–2510. doi: 10.1073/pnas.87.7.2506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 127.Hennet T., Peterhans E., Stocker R. Alterations in antioxidant defences in lung and liver of mice infected with influenza A virus. J. Gen. Virol. 1992;73:39–46. doi: 10.1099/0022-1317-73-1-39. [DOI] [PubMed] [Google Scholar]
  • 128.Dolganova A., Sharonov B. P. Application of various antioxidants in the treatment of influenza. Braz. J. Med. Biol. Res. 1997;30:1333–1336. doi: 10.1590/s0100-879x1997001100012. [DOI] [PubMed] [Google Scholar]
  • 129.Isakov, V. A., Chepik, E. B., Shamanova, M. G., et al. (1993) Current approaches to the treatment of severe influenza (Translated from Russian). Vestn. Ross. Akad. Med. Nauk. 10–13. [PubMed]
  • 130.Lowy R. J., Dimitrov D. S. Characterization of influenza virus-induced death of J774.1 macrophages. Exp. Cell Res. 1997;234:249–258. doi: 10.1006/excr.1997.3602. [DOI] [PubMed] [Google Scholar]

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