Improvements in SOD mimic AEOL-10150, a potent broad-spectrum antioxidant
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摘要
AEOL-10150 is a broad-spectrum metalloporphyrin superoxidase dismutase(SOD) mimic specifically designed to neutralize reactive oxygen and nitrogen species. Research has shown that AEOL-10150 is a potent medical countermeasure against national security threats including sulfur mustard(SM), nerve agent exposure and radiation pneumonitis following a radiological/nuclear incident sufficient to cause acute radiation syndrome(ARS). AEOL-10150 performed well in animal safety studies, and two completed phase 1 safety studies in patients demonstrated that the drug was safe and well tolerated, indicating that AEOL-10150 has potential as a new catalytic antioxidant drug. In this article, we review improvements in AEOL-10150 in preclinical pharmacodynamic studies, especially regarding anti-SM,chlorine gas and radiation exposure studies.
AEOL-10150 is a broad-spectrum metalloporphyrin superoxidase dismutase(SOD) mimic specifically designed to neutralize reactive oxygen and nitrogen species. Research has shown that AEOL-10150 is a potent medical countermeasure against national security threats including sulfur mustard(SM), nerve agent exposure and radiation pneumonitis following a radiological/nuclear incident sufficient to cause acute radiation syndrome(ARS). AEOL-10150 performed well in animal safety studies, and two completed phase 1 safety studies in patients demonstrated that the drug was safe and well tolerated, indicating that AEOL-10150 has potential as a new catalytic antioxidant drug. In this article, we review improvements in AEOL-10150 in preclinical pharmacodynamic studies, especially regarding anti-SM,chlorine gas and radiation exposure studies.
AEOL-10150 is a broad-spectrum metalloporphyrin superoxidase dismutase(SOD) mimic specifically designed to neutralize reactive oxygen and nitrogen species. Research has shown that AEOL-10150 is a potent medical countermeasure against national security threats including sulfur mustard(SM), nerve agent exposure and radiation pneumonitis following a radiological/nuclear incident sufficient to cause acute radiation syndrome(ARS). AEOL-10150 performed well in animal safety studies, and two completed phase 1 safety studies in patients demonstrated that the drug was safe and well tolerated, indicating that AEOL-10150 has potential as a new catalytic antioxidant drug. In this article, we review improvements in AEOL-10150 in preclinical pharmacodynamic studies, especially regarding anti-SM,chlorine gas and radiation exposure studies.
引文
1. Snider VG, Farquhar ER, Allen M, Abu-Spetani A, Mukherjee A. Design and reactivity of Ni-complexes using pentadentate neutral-polypyridyl ligands:possible mimics of NiSOD. J Inorg Biochem. 2017;175:110-7.
2. Batinic-Haberle I, Spasojevic I, Stevens RD, Hambright P, Fridovich I. Manganese(Ⅲ)meso-tetrakis(ortho-N-alkylpyridyl)porphyrins.Synthesis, characterization, and catalysis of O-2(center dot-)dismutation. J Chem Soc Dalton Trans. 2002;13:2689-96.
3. Batinic-Haberle I, Spasojevic I, Hambright P, Benov L, Crumbliss AL, Fridovich I. Relationship among redox potentials, proton dissociation constants of pyrrolic nitrogens, and in vivo and in vitro superoxide dismutating activities of manganese(Ⅲ)and iron(Ⅲ)water-soluble porphyrins. Inorg Chem. 1999; 38(18):4011-22.
4. Aeol Pharmaceuticals, California. 2017. http://www.marketwired.com/pressrelease/aeolus-announces-publication-datademonstrating-efficacy-aeol-10150-animal-model-lung-1877146.htm. Accessed 30 Dec 2017.
5. Hu P, Wu GW, Xia Q, Mao ZW. Achievement in SOD mimics with antioxidant and anti-inflammation functions. Prog Chem.2009;5(21):873-9.
6. Liang LP, Huang J, Fulton R, Fulton R, Pearson-Smith JN, Day BJ, Patel M. Pre-clinical therapeutic development of a series of metalloporphyrins for Parkinson's disease. Toxicol Appl Pharmacol. 2017;326:34-42.
7. Aeol pharmaceuticals, California. Aeolus Initiates Phase 1Study of AEOL 10150 in Healthy Normal Volunteers:Aeolus Pharmaceuticals(AOLS). 2017. https://finance.yahoo.com/n ews/aeolus-annou nce s-pre sen tation pharma co metricanalysis-1 20000901.html. Accessed 30 Dec 2017.
8. John Mcmanus. Aeolus receives BARDA decision regarding additional options for lung ARS development contract; files response to assertions made by BARDA in the notification:Aeolus pharmaceuticals(AOLS). 2017. http://www.andhranews.net/Business/2017/Aeolus-Receives-BARDADecision-RegardingAdditional-5767.htm. Accessed 30 Dec 2017.
9. Milano J, Day BJ. A catalytic antioxidant metalloporphyrin blocks hydrogen peroxide-induced mitochondrial DNA damage. Nucleic Acids Res. 2000; 28(4):968-73.
10. Bloodsworth A, O'Donnell VB, Batinic-Haberle I, Chumley PH, Hurt JB, Day BJ, et al. Manganese-porphyrin reactions with lipids and lipoproteins. Free Radic Biol Med. 2000;28(7):1017-29.
11. McElroy CS, Day BJ. Antioxidants as potential medical countermeasures for chemical warfare agents and toxic industrial chemicals. Biochem Pharmacol. 2016;100:1-11.
12. O'Neill HC, White CW, Veress LA, Hendry-HoferTB, Loader JE, Min E,et al. Treatment with the catalytic metalloporphyrin AEOL 10150reduces inflammation and oxidative stress due to inhalation of the sulfur mustard analog 2-chloroethyl ethyl sulfide. Free Radic Biol Med. 2010;48(9):1188-96.
13. O'Neill HC, Orlicky DJ, Hendry-Hofer TB, Loader JE, Day BJ, White CW. Role of reactive oxygen and nitrogen species in olfactory epithelial injury by the sulfur mustard analogue 2-chloroethyl ethyl sulfide. Am J Respir Cell Mol Biol. 2011;45(2):323-31.
14. Tewari-Singh N, Inturi S, Jain AK, Agarwal C, Orlicky DJ, White CW,et al. Catalytic antioxidant AEOL 10150 treatment ameliorates sulfur mustard analog 2-chloroethyl ethyl sulfide-associated cutaneous toxic effects. Free Radic Biol Med. 2014;72:285-95.
15. McElroy CS, Min E, Huang J, Loader JE, Hendry-Hofer TB, Garlick RB, et al. From the cover:catalytic antioxidant rescue of inhaled sulfur mustard toxicity.Toxicol Sci. 2016;154(2):341-53.
16. Chang W, Chen J, Schlueter CF, Rando RJ, Pathak YV, Hoyle GW. Inhibition of chlorine-induced lung injury by the type 4phosphodiesterase inhibitor rolipram. Toxicol Appl Pharmacol.2012;263(2):251-8.
17. White CW, Martin JG. Chlorine gas inhalation:human clinical evidence of toxicity and experience in animal models. Proc Am Thorac Soc. 2010;7(4):257-63.
18. McGovern T, Day BJ, White CW, Powell WS, Martin JG. AEOL10150:a novel therapeutic for rescue treatment after toxic gas lung injury. Free Radic Biol Med. 2011;50(5):602-8.
19. Wang JY, Mu XY, Li YH, Xu FJ, Long W, Yang J, et al. Hollow PtPdRh nanocubes with enhanced catalytic activities for in vivo clearanceof radiation-induced ROS via surface-mediated bond breaking.Small. 2018; 14(13):e1703736.
20. Xie J, Wang N, Dong X, Wang C, Du Z, Mei L, et al. Graphdiyne nanoparticles with high free radical scavenging activity for radiation protection. ACS Appl Mater Interfaces. 2018; https://doi.org/10.1021/acsami.8b00949.
21. Martinez RM, Fattori V, Saito P, Melo CBP, Borghi SM, Pinto IC, et al.Lipoxin A4 inhibits UV radiation-induced skin inflammation and oxidative stress in mice.J Dermatol Sci.2018;1811(18):30201-9.
22. Murigi FN, Mohindra P, Hung C, Salimi S, Goetz W, Pavlovic R,et al. Dose optimization study of AEOL 10150 as a mitigator of radiation-induced lung injury in CBA/J mice. Radiat Res.2015;184(4):422-32.
23. Shishkina LN. Peculiarities of antioxidants as radioprotectors under radiation damage of different extent. Radiats Biol Radioecol. 2013;53(5):536-44.(Article in Russian).
24. Thomson NC. Targeting oxidant-dependent mechanisms for the treatment of respiratory diseases and their comorbidities. Curr Opin Pharmacol. 2018;40:1-8.
25. Rabbani ZN, Batinic-Haberle I, Anscher MS, Huang J, Day BJ,Alexander E, et al. Long-term administration of a small molecular weight catalytic metalloporphyrin antioxidant AEOL 10150protects lungs from radiation induced injury. Int J Radiat Oncol Biol Phys. 2007;67(2):573-80.
26. MacVittie TJ, Gibbs A, Farese AM, Barrow K, Bennett A, TaylorHowell C. AEOL 10150 mitigates radiation-induced lung injury in the nonhuman primate:morbidity and mortality are administration schedule-dependent. Radiat Res.2017;187(3):298-318.
27. Garofalo MC, Ward AA, Farese AM, Bennett A, Taylor-Howell C, Cui WC, et al. A pilot study in rhesus macaques to assess the treatment efficacy of a small molecular weight catalytic metalloporphyrin antioxidant(AEOL 10150)in mitigating radiation-induced lung damage. Health Phys. 2014;106(1):73-83.
28. Salahuddin F, Rabbani Z, Yamnolenko P, Batinic-Haberle I,Thrasher B, Gauter-Fleckenstein B, et al. High dose of low molecular weight catalytic metalloporphyrin antioxidant AEOL10150 protects lungs from fractionated radiation. Int J Radiat Oncol Biol Phys. 2007;69(3):S484.
29. Rabbani ZN, Salahuddin FK, Yarmolenko P, Batinic-Haberle I, Thrasher BA, Gauter-Fleckenstein B, et al. Low molecular weight catalytic metalloporphyrin antioxidant AEOL 10150protects lungs from fractionated radiation. Free Radic Res.2007;41(11):1273-82.
30. Jackson IL, Zhang X, Hadley C, Hadley C, Rabbani ZN, Zhang Y,Marks S, et al. Temporal expression of hypoxia-regulated genes is associated with early changes in redox status in irradiated lung.Free Radic Biol Med. 2012;53(2):337-46.
31. Zhang Y, Zhang X, Rabbani ZN, Jackson IL, Vujaskovic Z. Oxidative stress mediates radiation lung injury by inducing apoptosis. Int J Radiat Oncol Biol Phys. 2012;83(2):740-8.
32. Sonis S, Patel M, Gammans R. AEOL 10150, a catalytic antioxidant,reduces the incidence and duration of radiation-induced oral mucositis in a hamster. Eur J Cancer. 2001;37(S6):S361.
33. Niemann B, Rohrbach S, Miller MR, Newby DE, Fuster V, Kovacic JC. Oxidative stress and cardiovascular risk:obesity, diabetes,smoking, and pollution:part 3 of a 3-part series.J Am Coll Cardiol.2017;70(2):230-51.
34. Smith KR, Uyeminami DL, Kodavanti UP, Crapo JD, Chang LY, Pinkerton KE. Inhibition of tobacco smoke-induced lunginflammation by a catalytic antioxidant. Free Radic Biol Med.2002;33(8):1106-14.
35. Pinkerton KE, Smith KR, Kodavanti U, Chang LY, Crapo JD.Attenuation of cigarette smoke-induced lung inflammation and remodeling by treatment with the metalloporphyrin(AEOL10150). Free Radic Biol Med. 2001;31:S49.
36. Rahman I, Kilty I. Antioxidant therapeutic targets in COPD. Curr Drug Targets. 2006;7(6):707-20.
37. Rahman I, Adcock IM. Oxidative stress and redox regulation of lung inflammation in COPD. Eur Respir J. 2006;28(1):219-42.
38. Rahman I. Antioxidant therapies in COPD. Int J Chron Obstruct Pulmon Dis. 2006;1(1):15-29.
39. Zuo L, Chuang CC, Clark AD, Garrison DE, Kuhlman JL, Sypert DC.Reactive oxygen species in COPD-related vascular remodeling.Adv Exp Med Biol. 2017;967:399-411.
40. Yu W, Gao D, Jin W, Liu S, Qi S. Propofol prevents oxidative stress by decreasing the ischemic accumulation of succinate in focal cerebral ischemia-reperfusion injury. Neurochem Res.2018;43(2):420-9.
41. Sheng H, Enghild JJ, Bowler R, Patel M, Batinic-Haberle I, Calvi CL, et al. Effects of metalloporphyrin catalytic antioxidants in experimental brain ischemia. Free Radic Biol Med.2002;33(7):947-61.
42. Warner DS, Homi H, Crapo JD, Pearlstein RD, Sheng H. Intravenous administration of the Mn metalloporphyrin catalytic antioxidant aeol 10150 protects against ischemic brain injury in mice. Society for Neuroscience Abstract Viewer and Itinerary Planner. 2002;Abstract No. 201.18.
43. Bowler RP, Sheng H, Enghild JJ, Pearlstein RD, Warner DS,Crapo JD. A catalytic antioxidant(AEOL 10150)attenuates expression of inflammatory genes in stroke. Free Radic Biol Med.2002;33(8):1141-52.
44. Liu XH, Harlow L, Graham ZA, Bauman WA, Cardozo C. Spinal cord injury leads to hyperoxidation and nitrosylation of skeletal muscle ryanodine receptor-1 associated with upregulation of nicotinamide adenine dinucleotide phosphate oxidase 4. J Neurotrauma. 2017;34(12):2069-74.
45. Sheng H, Spasojevic I, Warner DS, Batinic-Haberle I. Mn(iii)Meso Tetrakis(N,N'-diethylimidazolium-2-yl)porphyrin(AEOL-10150)offers protection in mouse model of spinal cord injury. Free Radic Biol Med.2003;35:S154.
46. Sheng H, Spasojevic I, Warner DS, Batinic-Haberle I. Mouse spinal cord compression injury is ameliorated by intrathecal cationic manganese(Ⅲ)porphyrin catalytic antioxidant therapy. Neurosci Lett. 2004;366(2):220-5.
47. Marrali G, Casale F, Salamone P, Fuda G, Caorsi C, Amoroso A, et al.NADPH oxidase(NOX2)activity is a modifier of survival in ALS. J Neurol. 2014; 261(11):2178-83.
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2. Batinic-Haberle I, Spasojevic I, Stevens RD, Hambright P, Fridovich I. Manganese(Ⅲ)meso-tetrakis(ortho-N-alkylpyridyl)porphyrins.Synthesis, characterization, and catalysis of O-2(center dot-)dismutation. J Chem Soc Dalton Trans. 2002;13:2689-96.
3. Batinic-Haberle I, Spasojevic I, Hambright P, Benov L, Crumbliss AL, Fridovich I. Relationship among redox potentials, proton dissociation constants of pyrrolic nitrogens, and in vivo and in vitro superoxide dismutating activities of manganese(Ⅲ)and iron(Ⅲ)water-soluble porphyrins. Inorg Chem. 1999; 38(18):4011-22.
4. Aeol Pharmaceuticals, California. 2017. http://www.marketwired.com/pressrelease/aeolus-announces-publication-datademonstrating-efficacy-aeol-10150-animal-model-lung-1877146.htm. Accessed 30 Dec 2017.
5. Hu P, Wu GW, Xia Q, Mao ZW. Achievement in SOD mimics with antioxidant and anti-inflammation functions. Prog Chem.2009;5(21):873-9.
6. Liang LP, Huang J, Fulton R, Fulton R, Pearson-Smith JN, Day BJ, Patel M. Pre-clinical therapeutic development of a series of metalloporphyrins for Parkinson's disease. Toxicol Appl Pharmacol. 2017;326:34-42.
7. Aeol pharmaceuticals, California. Aeolus Initiates Phase 1Study of AEOL 10150 in Healthy Normal Volunteers:Aeolus Pharmaceuticals(AOLS). 2017. https://finance.yahoo.com/n ews/aeolus-annou nce s-pre sen tation pharma co metricanalysis-1 20000901.html. Accessed 30 Dec 2017.
8. John Mcmanus. Aeolus receives BARDA decision regarding additional options for lung ARS development contract; files response to assertions made by BARDA in the notification:Aeolus pharmaceuticals(AOLS). 2017. http://www.andhranews.net/Business/2017/Aeolus-Receives-BARDADecision-RegardingAdditional-5767.htm. Accessed 30 Dec 2017.
9. Milano J, Day BJ. A catalytic antioxidant metalloporphyrin blocks hydrogen peroxide-induced mitochondrial DNA damage. Nucleic Acids Res. 2000; 28(4):968-73.
10. Bloodsworth A, O'Donnell VB, Batinic-Haberle I, Chumley PH, Hurt JB, Day BJ, et al. Manganese-porphyrin reactions with lipids and lipoproteins. Free Radic Biol Med. 2000;28(7):1017-29.
11. McElroy CS, Day BJ. Antioxidants as potential medical countermeasures for chemical warfare agents and toxic industrial chemicals. Biochem Pharmacol. 2016;100:1-11.
12. O'Neill HC, White CW, Veress LA, Hendry-HoferTB, Loader JE, Min E,et al. Treatment with the catalytic metalloporphyrin AEOL 10150reduces inflammation and oxidative stress due to inhalation of the sulfur mustard analog 2-chloroethyl ethyl sulfide. Free Radic Biol Med. 2010;48(9):1188-96.
13. O'Neill HC, Orlicky DJ, Hendry-Hofer TB, Loader JE, Day BJ, White CW. Role of reactive oxygen and nitrogen species in olfactory epithelial injury by the sulfur mustard analogue 2-chloroethyl ethyl sulfide. Am J Respir Cell Mol Biol. 2011;45(2):323-31.
14. Tewari-Singh N, Inturi S, Jain AK, Agarwal C, Orlicky DJ, White CW,et al. Catalytic antioxidant AEOL 10150 treatment ameliorates sulfur mustard analog 2-chloroethyl ethyl sulfide-associated cutaneous toxic effects. Free Radic Biol Med. 2014;72:285-95.
15. McElroy CS, Min E, Huang J, Loader JE, Hendry-Hofer TB, Garlick RB, et al. From the cover:catalytic antioxidant rescue of inhaled sulfur mustard toxicity.Toxicol Sci. 2016;154(2):341-53.
16. Chang W, Chen J, Schlueter CF, Rando RJ, Pathak YV, Hoyle GW. Inhibition of chlorine-induced lung injury by the type 4phosphodiesterase inhibitor rolipram. Toxicol Appl Pharmacol.2012;263(2):251-8.
17. White CW, Martin JG. Chlorine gas inhalation:human clinical evidence of toxicity and experience in animal models. Proc Am Thorac Soc. 2010;7(4):257-63.
18. McGovern T, Day BJ, White CW, Powell WS, Martin JG. AEOL10150:a novel therapeutic for rescue treatment after toxic gas lung injury. Free Radic Biol Med. 2011;50(5):602-8.
19. Wang JY, Mu XY, Li YH, Xu FJ, Long W, Yang J, et al. Hollow PtPdRh nanocubes with enhanced catalytic activities for in vivo clearanceof radiation-induced ROS via surface-mediated bond breaking.Small. 2018; 14(13):e1703736.
20. Xie J, Wang N, Dong X, Wang C, Du Z, Mei L, et al. Graphdiyne nanoparticles with high free radical scavenging activity for radiation protection. ACS Appl Mater Interfaces. 2018; https://doi.org/10.1021/acsami.8b00949.
21. Martinez RM, Fattori V, Saito P, Melo CBP, Borghi SM, Pinto IC, et al.Lipoxin A4 inhibits UV radiation-induced skin inflammation and oxidative stress in mice.J Dermatol Sci.2018;1811(18):30201-9.
22. Murigi FN, Mohindra P, Hung C, Salimi S, Goetz W, Pavlovic R,et al. Dose optimization study of AEOL 10150 as a mitigator of radiation-induced lung injury in CBA/J mice. Radiat Res.2015;184(4):422-32.
23. Shishkina LN. Peculiarities of antioxidants as radioprotectors under radiation damage of different extent. Radiats Biol Radioecol. 2013;53(5):536-44.(Article in Russian).
24. Thomson NC. Targeting oxidant-dependent mechanisms for the treatment of respiratory diseases and their comorbidities. Curr Opin Pharmacol. 2018;40:1-8.
25. Rabbani ZN, Batinic-Haberle I, Anscher MS, Huang J, Day BJ,Alexander E, et al. Long-term administration of a small molecular weight catalytic metalloporphyrin antioxidant AEOL 10150protects lungs from radiation induced injury. Int J Radiat Oncol Biol Phys. 2007;67(2):573-80.
26. MacVittie TJ, Gibbs A, Farese AM, Barrow K, Bennett A, TaylorHowell C. AEOL 10150 mitigates radiation-induced lung injury in the nonhuman primate:morbidity and mortality are administration schedule-dependent. Radiat Res.2017;187(3):298-318.
27. Garofalo MC, Ward AA, Farese AM, Bennett A, Taylor-Howell C, Cui WC, et al. A pilot study in rhesus macaques to assess the treatment efficacy of a small molecular weight catalytic metalloporphyrin antioxidant(AEOL 10150)in mitigating radiation-induced lung damage. Health Phys. 2014;106(1):73-83.
28. Salahuddin F, Rabbani Z, Yamnolenko P, Batinic-Haberle I,Thrasher B, Gauter-Fleckenstein B, et al. High dose of low molecular weight catalytic metalloporphyrin antioxidant AEOL10150 protects lungs from fractionated radiation. Int J Radiat Oncol Biol Phys. 2007;69(3):S484.
29. Rabbani ZN, Salahuddin FK, Yarmolenko P, Batinic-Haberle I, Thrasher BA, Gauter-Fleckenstein B, et al. Low molecular weight catalytic metalloporphyrin antioxidant AEOL 10150protects lungs from fractionated radiation. Free Radic Res.2007;41(11):1273-82.
30. Jackson IL, Zhang X, Hadley C, Hadley C, Rabbani ZN, Zhang Y,Marks S, et al. Temporal expression of hypoxia-regulated genes is associated with early changes in redox status in irradiated lung.Free Radic Biol Med. 2012;53(2):337-46.
31. Zhang Y, Zhang X, Rabbani ZN, Jackson IL, Vujaskovic Z. Oxidative stress mediates radiation lung injury by inducing apoptosis. Int J Radiat Oncol Biol Phys. 2012;83(2):740-8.
32. Sonis S, Patel M, Gammans R. AEOL 10150, a catalytic antioxidant,reduces the incidence and duration of radiation-induced oral mucositis in a hamster. Eur J Cancer. 2001;37(S6):S361.
33. Niemann B, Rohrbach S, Miller MR, Newby DE, Fuster V, Kovacic JC. Oxidative stress and cardiovascular risk:obesity, diabetes,smoking, and pollution:part 3 of a 3-part series.J Am Coll Cardiol.2017;70(2):230-51.
34. Smith KR, Uyeminami DL, Kodavanti UP, Crapo JD, Chang LY, Pinkerton KE. Inhibition of tobacco smoke-induced lunginflammation by a catalytic antioxidant. Free Radic Biol Med.2002;33(8):1106-14.
35. Pinkerton KE, Smith KR, Kodavanti U, Chang LY, Crapo JD.Attenuation of cigarette smoke-induced lung inflammation and remodeling by treatment with the metalloporphyrin(AEOL10150). Free Radic Biol Med. 2001;31:S49.
36. Rahman I, Kilty I. Antioxidant therapeutic targets in COPD. Curr Drug Targets. 2006;7(6):707-20.
37. Rahman I, Adcock IM. Oxidative stress and redox regulation of lung inflammation in COPD. Eur Respir J. 2006;28(1):219-42.
38. Rahman I. Antioxidant therapies in COPD. Int J Chron Obstruct Pulmon Dis. 2006;1(1):15-29.
39. Zuo L, Chuang CC, Clark AD, Garrison DE, Kuhlman JL, Sypert DC.Reactive oxygen species in COPD-related vascular remodeling.Adv Exp Med Biol. 2017;967:399-411.
40. Yu W, Gao D, Jin W, Liu S, Qi S. Propofol prevents oxidative stress by decreasing the ischemic accumulation of succinate in focal cerebral ischemia-reperfusion injury. Neurochem Res.2018;43(2):420-9.
41. Sheng H, Enghild JJ, Bowler R, Patel M, Batinic-Haberle I, Calvi CL, et al. Effects of metalloporphyrin catalytic antioxidants in experimental brain ischemia. Free Radic Biol Med.2002;33(7):947-61.
42. Warner DS, Homi H, Crapo JD, Pearlstein RD, Sheng H. Intravenous administration of the Mn metalloporphyrin catalytic antioxidant aeol 10150 protects against ischemic brain injury in mice. Society for Neuroscience Abstract Viewer and Itinerary Planner. 2002;Abstract No. 201.18.
43. Bowler RP, Sheng H, Enghild JJ, Pearlstein RD, Warner DS,Crapo JD. A catalytic antioxidant(AEOL 10150)attenuates expression of inflammatory genes in stroke. Free Radic Biol Med.2002;33(8):1141-52.
44. Liu XH, Harlow L, Graham ZA, Bauman WA, Cardozo C. Spinal cord injury leads to hyperoxidation and nitrosylation of skeletal muscle ryanodine receptor-1 associated with upregulation of nicotinamide adenine dinucleotide phosphate oxidase 4. J Neurotrauma. 2017;34(12):2069-74.
45. Sheng H, Spasojevic I, Warner DS, Batinic-Haberle I. Mn(iii)Meso Tetrakis(N,N'-diethylimidazolium-2-yl)porphyrin(AEOL-10150)offers protection in mouse model of spinal cord injury. Free Radic Biol Med.2003;35:S154.
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