protective effects of myrtol standardized against radiation induced lung injury

Physiol Biochem 2016;38:619-634 Cellular Physiology Cell © 2016 The Author(s) Published by S Karger AG, Basel DOI: 10.1159/000438655 DOI: 10.1159/000438655 © 2016 The Author(s) online:February February 2016 www.karger.com/cpb Published online: 08,08, 2016 Published by S Karger AG, Basel and Biochemistry Published 1421-9778/16/0382-0619$39.50/0 619 Zhao et al.: Myrtol Standardized on Radiation-Induced Lung Injury Accepted: December 28, 2015 www.karger.com/cpb This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND) (http://www.karger.com/Services/OpenAccessLicense) Usage and distribution IRUFRPPHUFLDOSXUSRVHVDVZHOODVDQ\GLVWULEXWLRQRIPRGLÀHGPDWHULDOUHTXLUHVZULWWHQSHUPLVVLRQ Original Paper Protective Effects of Myrtol Standardized Against Radiation-Induced Lung Injury De-yun Zhao Hong-jin Qu Jia-ming Guo Hai-nan Zhao Yan-yong Yang Pei Zhang Kun Cao Xiao Lei Jian-guo Cui Cong Liu Jian-ming Cai Fu Gao Bai-long Li Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, China Key Words Radiation-induced lung injury • Myrtol standardized •3XOPRQDU\ÀEURVLV Abstract Background/Aims: As a major complication after thoracic radiotherapy, radiation-induced OXQJLQMXU\5,/,KDVJUHDWLPSDFWRQORQJWHUPTXDOLW\RIOLIHDQGFRXOGUHVXOWLQIDWDOUHVSLUDWRU\ LQVXIÀFLHQF\7KHSUHVHQWVWXG\ZDVDLPHGWRHYDOXDWHWKHHIIHFWVRI0\UWROVWDQGDUGL]HGRQ RILI, and to investigate the underlying mechanism Methods: A mouse model of radiationinduced lung injury was generated by using thoracic irradiation with a single dose of 16Gy Mice were orally administrated with Myrtol (25 mg/kg/day) for weeks after irradiation, while prednisone (5 mg/kg/day) was used as a positive control After then, the body weight and lung FRHIÀFLHQW ZHUH FDOFXODWHG 7KH VHYHULW\ RI ÀEURVLV ZDV HYDOXDWHG E\ REVHUYLQJ SXOPRQDU\ sections after radiation and collagen content in lung tissues was calculated following the hydroxyproline (HYP) assay Pathological changes were observed in all the groups by using +(VWDLQLQJDQG0DVVRQVWDLQLQJ7KHVHUXPOHYHOVRI7*)DŽ71)į,/DŽ,/DQG3*( were also measured with an ELISA assay Western blot assay was used to measure the impact of Myrtol on AKT and its downstream signaling pathway, including MMP-2 and MMP-9 The OHYHOV RI 9LPHQWLQ DQG į60$ ZHUH HYDOXDWHG ZLWK DQ LPPXQRÁXRUHVFHQFH DVVD\ Results: 7UHDWPHQWZLWK0\UWROVWDQGDUGL]HGEXWQRWSUHGQLVRQHUHGXFHGOXQJFRHIÀFLHQWDQGFROODJHQ deposition in lung tissues, while attenuated histological damages induced by irradiation Myrtol standardized also reduced the production of MDA, while increased the level of SOD It ZDVDOVRREVHUYHGWKDW0\UWROVWDQGDUGL]HGLQKLELWHG7*)DŽDQGDVHULHVRISURLQÁDPPDWRU\ F\WRNLQHVLQFOXGLQJ71)į,/DŽ,/3*(:KLOHLQSUHGQLVRQHJURXSHYHQWKRXJKWKHHDUO\ pneumonitis was ameliorated, the collagen disposition remained unchanged in latter times ,PPXQRÁXRUHVFHQFH DQDO\VLV DOVR UHYHDOHG HOHYDWLRQ RI YLPHQWLQ DQG į60$ LQ WKH DOYHROL after a single dose of 16Gy Conclusion: The present results suggest Myrtol standardized as an effective agent for attenuating the lung injury induced by irradiation © 2016 The Author(s) Published by S Karger AG, Basel Bailong Li, Fu Gao and Jianming Cai Department of Radiation Medicine, Faculty of Naval Medicine, Military Medical Building, Second Military Medical University, Room 1102, 11/F, NO 800, Xiangyin Road, Shanghai 200433, (China) E-Mail libailong2013@163.com; E-Mail gaofusmmu@163.com; E-Mail cjm882003@163.com Downloaded by: Univ of California San Diego 132.239.1.231 - 3/3/2017 8:59:18 AM '=KDR+4XDQG-*XRFRQWULEXWHGHTXDOO\WRWKLVZRUN Physiol Biochem 2016;38:619-634 Cellular Physiology Cell © 2016 The Author(s) Published by S Karger AG, Basel DOI: 10.1159/000438655 and Biochemistry Published online: February 08, 2016 www.karger.com/cpb 620 Zhao et al.: Myrtol Standardized on Radiation-Induced Lung Injury Introduction Thoracic radiotherapy (RT) is a common therapeutic modality for treating lung cancer, esophageal cancer, lymphoma and thymoma cancer RT-induced lung injuries are traditionally divided into early (acute, 1-6 months post-RT) pneumonitis and late (chronic, ͸‘–Š•’‘•–ǦȌϐ‹„”‘•‹•†‡’‡†‹‰‘–Š‡–‹‡ƒˆ–‡””ƒ†‹ƒ–‹‘‡š’‘•—”‡ȏͳǡʹȐǤ Previous data showed that radiation therapy induced lung injury was fairly common, ‘……—””‹‰‹ƒ„‘—–ͷΨ–‘͵͹Ψ‘ˆ’ƒ–‹‡–•™‹–ŠŽ—‰…ƒ…‡”ȏ͵ȐǤŠ‡…—””‡–…Ž‹‹…ƒŽ–”‡ƒ–‡– ˆ‘””ƒ†‹ƒ–‹‘Ǧ‹†—…‡†Ž—‰‹Œ—”›’”‹ƒ”‹Ž›‹˜‘Ž˜‡†…Š‡‹…ƒŽƒ–‹Ǧ‹ϐŽƒƒ–‘”›ƒ‰‡–•ƒ† ‹—‘•—’’”‡••‹˜‡ …›–‘‹‡•ǡ ƒ–‹‘š‹†ƒ– ƒ‰‡–•ǡ •—…Š ƒ• …‘”–‹…‘•–‡”‘‹†• ‘” Ǧɀ ȏͶȐǤ Š‡•‡†”—‰•…‘—Ž†ƒ––‡—ƒ–‡ƒ…—–‡‹ϐŽƒƒ–‹‘ˆ‘”ʹǦ͵‘–Š•ƒˆ–‡”‹””ƒ†‹ƒ–‹‘ǡ„—––Š‡› …‘—Ž† ‘– ‡ˆˆ‡…–‹˜‡Ž› ‹–‹‰ƒ–‡ ϐ‹„”‘‰‡‹… ’”‘…‡••‡• ‹ Žƒ––‡” •–ƒ‰‡ ȏͷȐǤ —”–Š‡”‘”‡ǡ –Š‡•‡ ƒ‰‡–• …‘—Ž† …ƒ—•‡ •‹‰‹ϐ‹…ƒ– •‹†‡Ǧ‡ˆˆ‡…–•ǡ ‹…Ž—†‹‰ ‹ˆ‡…–‹‘•ǡ ˜‘‹–‹‰ǡ ƒ† ‡˜‡ †‡ƒ–Š ™Š‹…ŠŽ‹‹–•–Š‡‹”ƒ’’Ž‹…ƒ–‹‘‹…Ž‹‹…•ȏ͸ȐǤ Ž–Š‘—‰Š –Š‡ ‘Ž‡…—Žƒ” ‡…Šƒ‹•• ‘ˆ ”ƒ†‹ƒ–‹‘Ǧ‹†—…‡† Ž—‰ ‹Œ—”› Šƒ˜‡ ‘– „‡‡ ‘–ˆ—ŽŽ›—†‡”•–‘‘†ǡƒ•‡”‹‡•‘ˆ’”‘Ǧ‹ϐŽƒƒ–‘”›…›–‘‹‡•ƒ†‰”‘™–Šˆƒ…–‘”•ƒ”‡•Š‘™ –‘ ’Žƒ› ‹’‘”–ƒ– ”‘Ž‡• ‹ –Š‡ ”ƒ†‹ƒ–‹‘Ǧ‹†—…‡† Ž—‰ ‹Œ—”›ǡ „‡…ƒ—•‡ –Š‡› ’”‘‘–‡ ‡ƒ”Ž› ‹ϐŽƒƒ–‹‘ƒ†Žƒ––‡”’Šƒ•‡ϐ‹„”‘•‹•ȏ͹Ȑǡ‹…”‡ƒ•‡–Š‡†‡’‘•‹–‹‘‘ˆƒ–”‹š’”‘–‡‹•ǡƒ† could also distort the pulmonary architecture and respiratory function Therefore, reducing ’”‘Ǧ‹ϐŽƒƒ–‘”› …›–‘‹‡• ”‡Ž‡ƒ•‡ ƒ† ‘š‹†ƒ–‹˜‡ •–”‡•• ”‡’”‡•‡–• ’‘••‹„Ž‡ –Š‡”ƒ’‡—–‹… strategies ‡”„ƒŽ‡†‹…‹‡‹•˜‡”›’‘’—Žƒ”‹•‹ƒƒ†—”‘’‡ƒ…‘—–”‹‡•Ǥ‘‰–Š‘•‡ǡ›”–‘Ž •–ƒ†ƒ”†‹œ‡† ȋǦ‘ǤͺͲͲʹǦͷͷǦͻȌ ‹• ƒ ’Š›–‘–Š‡”ƒ’‡—–‹… ‡š–”ƒ…– ˆ”‘ Myrtus communis, such as Pinusspp(pine), Citrusaurantifolia(lime) and Eucalyptus globulus, mainly containing –Š”‡‡‘‘–‡”’‡‡•ǣͳǡͺǦ…‹‡‘Ž‡ǡȽǦ’‹‡‡ƒ††Ž‹‘‡‡ƒ•ƒ”‡”•—„•–ƒ…‡•Ǥ–Šƒ•„‡‡ ™‹†‡Ž›—•‡†‹–Š‡–”‡ƒ–‡–‘ˆƒ…—–‡ƒ†…Š”‘‹…Ž—‰†‹•‡ƒ•‡ȏͺǡͻȐǤ —”–Š‡”‘”‡ǡ‹–Šƒ•„‡‡ ˆ‘—† –Šƒ– ‹– Šƒ• ƒ–‹Ǧ‹ϐŽƒƒ–‘”›ǡ ƒ–‹„ƒ…–‡”‹ƒŽǡ ƒ–‹‘š‹†ƒ–ǡ ƒ–‹ǦƒŽŽ‡”‰‹…ǡ ƒ–‹‹…”‘„‹ƒŽ ƒ† ƒ•ƒŽ —…‘…‹Ž‹ƒ”› …Ž‡ƒ”‹‰ ‡ˆˆ‡…–• ȏͳͲǦͳ͸ȐǤ  ƒ††‹–‹‘ǡ –Š‡ ͷͲ ˜ƒŽ—‡ ‘ˆ ›”–‘Ž ‹• ‰”‡ƒ–‡”–Šƒ͵ͷͲͲ‰Ȁ‰‘ˆ–Š‡„‘†›™‡‹‰Š–ǡˆƒ”‘”‡–Šƒ–”‡ƒ–‡– …‘…‡–”ƒ–‹‘ȋʹͷ ‰Ȁ‰Ȁ†ƒ›Ȍ™Š‡ƒ†‹‹•–‡”‡†‘”ƒŽŽ›˜‹ƒ‰ƒ•–”‹…‹–—„ƒ–‹‘Ǥ”‘Ž‘‰‡†ƒ†‹‹•–”ƒ–‹‘‘ˆ –Š‡›”–‘Ž™ƒ•™‡ŽŽ–‘Ž‡”ƒ–‡†ƒ†™ƒ•‘„•‡”˜‡†‘–‘š‹…‹–›Ǥ –Š‡’”‡•‡–•–—†›ǡ™‡†‡‘•–”ƒ–‡†–Šƒ–‘”ƒŽƒ†‹‹•–”ƒ–‹‘‘ˆ›”–‘Ž…‘—Ž†ƒŽŽ‡˜‹ƒ–‡ radiation-induced lung injury To investigate the underlying mechanism for the involvement ‘ˆ›”–‘Ž‹”ƒ†‹ƒ–‹‘Ǧ‹†—…‡†Ž—‰‹Œ—”›ǡ™‡‡šƒ‹‡†–Š‡‡ˆˆ‡…–•‘ˆ›”–‘Ž–”‡ƒ–‡–‘ •‹‰ƒŽ‹‰’ƒ–Š™ƒ›ƒ†‹–•†‘™•–”‡ƒǦʹƒ†ǦͻŽ‡˜‡Ž•‹‹””ƒ†‹ƒ–‡†‹…‡Ǥ Animals and treatment ŽŽ–Š‡’”‘–‘…‘Ž•™‡”‡ƒ’’”‘˜‡†„›–Š‡‹ƒŽ–Š‹…•‘‹––‡‡‘ˆ‡…‘†‹Ž‹–ƒ”›‡†‹…ƒŽ‹˜‡”•‹–›ǡ Š‹ƒǡ‹ƒ……‘”†ƒ…‡™‹–Š–Š‡ —‹†‡ˆ‘”ƒ”‡ƒ†•‡‘ˆƒ„‘”ƒ–‘”›‹ƒŽ•’—„Ž‹•Š‡†„›–Š‡ƒ–‹‘ƒŽ •–‹–—–‡‘ˆ‡ƒŽ–Šȋ’—„Ž‹…ƒ–‹‘‘Ǥͻ͸ǦͲͳȌǤ ‹„”‘•‹•’”‘‡‹…‡ͺ™‡‡Ǧ‘Ž†ˆ‡ƒŽ‡ͷ͹Ȁ͸‹…‡™‹–Šƒ ƒ’’”‘š‹ƒ–‡™‡‹‰Š–‘ˆͳͺȂʹͲ‰™‡”‡‘„–ƒ‹‡†ˆ”‘–Š‡š’‡”‹‡–ƒŽ‹ƒŽ‡–‡”‘ˆŠ‹‡•‡…ƒ†‡› of Sciences, Shanghai, China) were used and randomly divided into four groups as follows: group 1, non‹””ƒ†‹ƒ–‡†…‘–”‘Žȋα͵ͲȌǢ‰”‘—’ʹǡ‹””ƒ†‹ƒ–‹‘Ϊ•ƒŽ‹‡ȋα͵ͲȌǢ‰”‘—’͵ǡ‹””ƒ†‹ƒ–‹‘Ϊ›”–‘Žȋα͵Ͳǡʹͷ ‰Ȁ‰Ȁ†ƒ›Ȍƒ†‰”‘—’Ͷ‹””ƒ†‹ƒ–‹‘Ϊ’”‡†‹•‘‡ȋα͵Ͳǡͷ‰Ȁ‰Ȁ†ƒ›ȌǤ‹…‡™‡”‡‡’–—†‡”•–ƒ†ƒ”† Žƒ„‘”ƒ–‘”›…‘†‹–‹‘•ȋʹʹάʹιǡͷͷάͳͲΨŠ—‹†‹–›ƒ†ͳʹǦͳʹŠȀŽ‹‰Š–Ǧ†ƒ”…›…Ž‡Ȍǡ†—”‹‰™Š‹…Š•–‡”‹Ž‹œ‡† ˆ‘‘†ƒ†™ƒ–‡”™‡”‡•—’’Ž‹‡†ƒ†Ž‹„‹–—Ǥ‹…‡™‡”‡ƒŽŽ‘™‡†–‘ƒ……Ž‹ƒ–‡ˆ”‘ƒ‹ƒŽ…‡–‡”ˆ‘”ͳ™‡‡ ’”‹‘”–‘–”‡ƒ–‡–Ǥ›”–‘Ž•–ƒ†ƒ”†‹œ‡†ȋ ‡Ž‘›”–‘ŽȌ™ƒ•‘„–ƒ‹‡†ˆ”‘ Ǥ‘ŠŽǦ‘•ƒ’ „Ƭ‘Ǥ  ȋ‘Š‡Ž‘…•–‡†–ǡ ‡”ƒ›ȌǤ›”–‘Ž•–ƒ†ƒ”†‹œ‡†™ƒ•‰‹˜‡‘”ƒŽŽ›ƒ™‡‡„‡ˆ‘”‡‹””ƒ†‹ƒ–‹‘ƒ–ƒ†‘•‡‘ˆ ʹͷ ‰Ȁ‰Ȁ†ƒ› ƒ† ƒ‹–ƒ‹‡† ȋʹͷ ‰Ȁ‰Ȁ†ƒ›Ȍ —–‹Ž Ͷ ™‡‡• ƒˆ–‡” ‹””ƒ†‹ƒ–‹‘Ǥ ”‡†‹•‘‡ ȋ  ǤǡǡŠƒ‰Šƒ‹ǡŠ‹ƒȌ™ƒ•ƒ†‹‹•–‡”‡†‘”ƒŽŽ›ͷ‰Ȁ‰†ƒ‹Ž›’‘•–‹””ƒ†‹ƒ–‹‘ˆ‘”Ͷ™‡‡•Ǥ Downloaded by: Univ of California San Diego 132.239.1.231 - 3/3/2017 8:59:18 AM Materials and Methods Physiol Biochem 2016;38:619-634 Cellular Physiology Cell © 2016 The Author(s) Published by S Karger AG, Basel DOI: 10.1159/000438655 and Biochemistry Published online: February 08, 2016 www.karger.com/cpb 621 Zhao et al.: Myrtol Standardized on Radiation-Induced Lung Injury Irradiation ‹…‡™‡”‡‹””ƒ†‹ƒ–‡†—•‹‰͸Ͳ‘‹””ƒ†‹ƒ–‘”ȋ””ƒ†‹ƒ–‹‘‡–‡”‘ˆ‡…‘†‹Ž‹–ƒ”›‡†‹…ƒŽ‹˜‡”•‹–›Ȍ ƒ–ƒ†‘•‡”ƒ–‡‘ˆδͳ ›Ȁ‹Ǥˆ–‡”ƒ‡•–Š‡–‹œƒ–‹‘™‹–ŠͳͲΨ…ŠŽ‘”ƒŽŠ›†”ƒ–‡ȋ͵ͷͲ‰Ȁ‰Ȍǡ–Š‡‹…‡™‡”‡ ’—– ‹ ƒ Š‘Ž†‡” †‡•‹‰‡† –‘ ‹‘„‹Ž‹œ‡ ƒƒ‡•–Š‡–‹œ‡† ‹…‡ •‘ –Šƒ– ‘Ž› –Š‡ ™Š‘Ž‡ –Š‘”ƒš ™ƒ• ‡š’‘•‡† –‘–Š‡„‡ƒǤ ”‘—’•‘ˆ‹…‡ȋα͵ͲȌ”‡…‡‹˜‡†ƒ•‹‰Ž‡†‘•‡‘ˆ–Š‘”ƒ…‹…‹””ƒ†‹ƒ–‹‘ȋͳ͸ ›ȌǤ‹ƒŽ•™‡”‡ ‘‹–‘”‡†—’–‘ͳ͸™‡‡•’‘•–Ǧ‹””ƒ†‹ƒ–‹‘ǡƒ†–Š‡„‘†›™‡‹‰Š–™ƒ•”‡…‘”†‡†ƒ–‡ƒ…Š–‹‡’‘‹–ȋͳǡʹǡͶǡͺǡ 16 weeks post-irradiation) Sample collection and initial processing ‹š‹…‡ƒ–‡ƒ…Š–‹‡’‘‹–ȋͳǡʹǡͶǡͺƒ†ͳ͸™‡‡•’‘•–Ǧ‹””ƒ†‹ƒ–‹‘Ȍˆ”‘–”‡ƒ–‡†ƒ†…‘–”‘Ž‰”‘—’ ™‡”‡ •ƒ…”‹ϐ‹…‡† „› …‡”˜‹…ƒŽ †‹•Ž‘…ƒ–‹‘Ǥ ˆ–‡” ‡ƒ•—”‹‰ „‘†› ™‡‹‰Š–ǡ …ƒ”†‹ƒ… ’—…–—”‡ ™ƒ• ’‡”ˆ‘”‡† –‘‘„–ƒ‹ƒ„‘—–ͷͲͲɊ„Ž‘‘†ǤŠ‡„Ž‘‘†™ƒ•ƒŽŽ‘™‡†–‘…Ž‘–ƒ–”‘‘–‡’‡”ƒ–—”‡ˆ‘”ͳǤͷǦʹŠƒ†–Š‡ …‡–”‹ˆ—‰‡†ƒ–͵ǡͷͲͲ”’ǡͶιˆ‘”ͳͷ‹—–‡•ǤŠ‡•‡”—™ƒ•…‘ŽŽ‡…–‡†ƒ†•–‘”‡†ƒ–ǦͺͲιˆ‘”Žƒ––‡”‡œ›‡Ǧ Ž‹‡†‹—‘•‘”„‡–ƒ••ƒ›ȋȌǤŠ‡™‡–™‡‹‰Š–‘ˆ–Š‡Ž—‰•™‡”‡”‡…‘”†‡†ˆ‘”‡ƒ…Š‘—•‡ǡ‘‡’ƒ”– ‘ˆ”‹‰Š–Ž—‰•™‡”‡ϐ‹š‡†™‹–ŠͶΨ’ƒ”ƒˆ‘”ƒŽ†‡Š›†‡ˆ‘”Š‹•–‘Ž‘‰‹…ƒŽƒ†‹—‘ϐŽ—‘”‡•…‡…‡ƒƒŽ›•‹•ǤŠ‡ ”‡•–‘ˆ–Š‡Ž—‰•™‡”‡†‹˜‹†‡†‹–‘ϐ‹˜‡’ƒ”–•ƒ†‡’–ƒ–ǦͺͲǑˆ‘”†‡–‡”‹ƒ–‹‘‘ˆŽ‹’‹†’‡”‘š‹†‡•ȋȌǡ ƒ…–‹˜‹–‹‡•ǡ›†”‘š›’”‘Ž‹‡ǡǦƒ†‡•–‡”„Ž‘–‡ƒ•—”‡‡–ǡ”‡•’‡…–‹˜‡Ž›Ǥ ‘†›™‡‹‰Š–ƒ†—‰…‘‡ˆϔ‹…‹‡– Š‡„‘†›™‡‹‰Š–™ƒ•‡ƒ•—”‡†ƒ–ͳǡʹǡͶǡͺƒ†ͳ͸™‡‡•’‘•–Ǧ‹””ƒ†‹ƒ–‹‘ǤŠ‡”ƒ–‹‘‘ˆ–Š‡Ž—‰™‡– ™‡‹‰Š–ȋ‰Ȍ–‘„‘†›™‡‹‰Š–ȋ‰ȌȋŽ—‰™‡‹‰Š–Ȁ„™Ȍ™ƒ•—•‡†ƒ•–Š‡Ž—‰…‘‡ˆϐ‹…‹‡–Ǥ Measurement of lungs collagen content, MDA, SOD activity Š‡ …‘…‡–”ƒ–‹‘ ‘ˆ Š›†”‘š›’”‘Ž‹‡ ™ƒ• ‡ƒ•—”‡† „› Š›†”‘š›’”‘Ž‹‡ ȋ›’Ȍ ƒ••ƒ› ‹– ȋƒŒ‹‰ ‹ƒ…Š‡‰‹‘‡‰‹‡‡”‹‰•–‹–—–‡ǡƒŒ‹‰ǡŠ‹ƒȌƒ……‘”†‹‰–‘–Š‡ƒ—ˆƒ…–—”‡”ǯ•’”‘–‘…‘ŽǤ’’”‘š‹ƒ–‡Ž› ͷͲǦͳͲͲ‰‘ˆŽ—‰–‹••—‡™ƒ•Š›†”‘Ž›œ‡†‹͸ͲͲ—‘ˆŽ›•‹•„—ˆˆ‡”•‘Ž—–‹‘ƒ–™ƒ–‡”„ƒ–Š‡––Ž‡ƒ–ͻͻιˆ‘” ʹͲ ‹ „Ž‡†‹‰ ‡˜‡”› ͳͲ ‹—–‡•Ǥ ˆ–‡” …‘‘Ž‹‰ǡ –Š‡ ƒ„•‘”„ƒ…‡ ‘ˆ …‘Ž‘”‡† ’”‘†—…–• ™ƒ• ‡ƒ•—”‡† ƒ– ͷͷͲ—•‹‰ƒƒ”‹‘•ƒ—Ž–‹‘†‡‹…”‘’Žƒ–‡‡ƒ†‡”ȋŠ‡”‘ ‹•Š‡”…‹‡–‹ϐ‹……ǤƒŽ–Šƒǡǡ Ȍ–‘‡˜ƒŽ—ƒ–‡…‘ŽŽƒ‰‡†‡’‘•‹–‹‘Ǥ ƒŽ‘†‹ƒŽ†‡Š›†‡ȋȌ…‘–‡–ƒ†ƒ…–‹˜‹–›‹Ž—‰–‹••—‡™‡”‡‡ƒ•—”‡†—•‹‰…‘‡”…‹ƒŽ‹œ‡† …Š‡‹…ƒŽƒ••ƒ›‹–•ƒ……‘”†‹‰–‘–Š‡ƒ—ˆƒ…–—”‡”ǯ•’”‘–‘…‘ŽȋƒŒ‹‰ ‹ƒ…Š‡‰‹‘‡‰‹‡‡”‹‰•–‹–—–‡ǡ ƒŒ‹‰ǡŠ‹ƒȌƒ†–Š‡–‘–ƒŽ’”‘–‡‹…‘…‡–”ƒ–‹‘™ƒ•†‡–‡”‹‡†„›ȋ‹…‹…Š‘‹‹……‹†Ȍ’”‘–‡‹ ƒ••ƒ›‹–ȋ‡›‘–‹‡•–‹–—–‡‘ˆ‹‘–‡…Š‘Ž‘‰›ǡƒ–‘‰ǡŠ‹ƒȌǤ —‘ϔŽ—‘”‡•…‡…‡•–ƒ‹‹‰ —‘ϐŽ—‘”‡•…‡…‡ ƒƒŽ›•‹• ™ƒ• ’‡”ˆ‘”‡† –‘ ‹†‡–‹ˆ› –Š‡ ‡š’”‡••‹‘ ‘ˆ ȽǦ ƒ† ˜‹‡–‹ǡ ‡•‡…Š›ƒŽ…‡ŽŽƒ”‡”‹–Š‡Ž—‰–‹••—‡Ǥ”‹‡ϐŽ›ǡƒˆ–‡”†‡’ƒ”ƒˆϐ‹‹œƒ–‹‘ǡƒ–‹‰‡”‡–”‹‡˜ƒŽǡƒ†‹…—„ƒ–‹‘ ™‹–Š‘†‡–Ž‘…ƒ•†‡•…”‹„‡†ȏͳͺȐǡ–Š‡•‡…–‹‘•™‡”‡‹…—„ƒ–‡†™‹–Šƒ‹š–—”‡‘ˆƒ–‹ǦȽǦȋͳǣͷͲͲǡ „…ƒǡƒ„”‹†‰‡ǡȌƒ†ƒ–‹Ǧ˜‹‡–‹ȋͳǣͳͲͲͲǡ„…ƒǡƒ„”‹†‰‡ǡȌƒ–‹„‘†‹‡•ƒ–Ͷι‘˜‡”‹‰Š–Ǥ ˆ–‡”™ƒ•Š‹‰™‹–Šǡ–Š‡•‡…–‹‘•™‡”‡‹…—„ƒ–‡†™‹–Š …‘Œ—‰ƒ–‡†Ž‡šƒ Ž—‘”Ͷͺͺ‰‘ƒ–ƒ–‹Ǧ‘—•‡ ȋ˜‹–”‘‰‡ǡ ƒ”Ž•„ƒ†ǡ Ȍ ƒ† ‡šƒ• ‡†Ǧ…‘Œ—‰ƒ–‡† ƒ–‹Ǧ”ƒ„„‹– •‡…‘†ƒ”› ƒ–‹„‘†‹‡• ȋ„…ƒȌ ƒ– ”‘‘ –‡’‡”ƒ–—”‡ ˆ‘” ͵Ͳ ‹Ǥ —…Ž‡‹ ™‡”‡ …‘—–‡”•–ƒ‹‡† ™‹–Š  †‹Š›†”‘…ŠŽ‘”‹†‡ǡ ƒ† –Š‡ •‡…–‹‘• ™‡”‡ ƒƒŽ›œ‡†—•‹‰ƒϐŽ—‘”‡•…‡…‡‹…”‘•…‘’‡ȋ‹‘…Ž‹’•‡‹Ǧǡ‹‘ǡ‘›‘ǡ ƒ’ƒȌǤ Downloaded by: Univ of California San Diego 132.239.1.231 - 3/3/2017 8:59:18 AM Pathological examination ……‘”†‹‰–‘–Š‡‡–Š‘†‘Ž‘‰›†‡•…”‹„‡†„›•Š…”‘ˆ–‡–ƒŽ.ȏͳ͹Ȑ•…‘”‹‰•›•–‡ǡŽ—‰•‡…–‹‘••–ƒ‹‡† ™‹–Š Ƭ ƒ† ƒ••‘ǯ• –”‹…Š”‘‡ ™‡”‡ …ƒ””‹‡† ‘—– ™‹–Š •Š…”‘ˆ– •…‘”‡ ƒ† ƒ “—ƒ–‹ˆ›‹‰ ƒ••ƒ›‹…ƒ–‹‘ ‘ˆ ƒ••‘ǯ• –”‹…Š”‘‡ǡ ”‡•’‡…–‹˜‡Ž›Ǥ ”‹‡ϐŽ›ǡ –Š‡ •‡˜‡”‹–› ‘ˆ ϐ‹„”‘•‹• ™ƒ• ‰”ƒ†‡† ƒ† •…‘”‡† ‘ ƒ •…ƒŽ‡ ‘ˆ ͲȂͺǤ‡ϐ‹‡Ž†•’‡”•‡…–‹‘ƒ–έʹͲͲƒ‰‹ϐ‹…ƒ–‹‘•™‡”‡”ƒ†‘Ž›•‡Ž‡…–‡†’‡”‘—•‡ǡƒ†–™‘„Ž‹†‡† ’ƒ–Š‘Ž‘‰‹•–•…ƒ”‡ˆ—ŽŽ›ƒ†‹†‡’‡†‡–Ž›‡šƒ‹‡†͸Ͳϐ‹‡Ž†•’‡”‰”‘—’—•‹‰‹‘Ǧ ‹ͳǦʹ‹…”‘•…‘’‡ ȋ‹‘ǡ‘›‘ǡ ƒ’ƒȌǤŠ‡‡ƒ•…‘”‡‘ˆƒŽŽϐ‹‡Ž†•‡šƒ‹‡†™ƒ•–ƒ‡ƒ•–Š‡ϐ‹„”‘•‹••…‘”‡ƒ†’‘•‹–‹˜‡ ”ƒ–‡ȋΨȌ‘ˆ‡ƒ…Šƒ‹ƒŽǤ Physiol Biochem 2016;38:619-634 Cellular Physiology Cell © 2016 The Author(s) Published by S Karger AG, Basel DOI: 10.1159/000438655 and Biochemistry Published online: February 08, 2016 www.karger.com/cpb 622 Zhao et al.: Myrtol Standardized on Radiation-Induced Lung Injury ELISA assays ‡”— Ž‡˜‡Ž• ‘ˆ  ǦȾͳǡ  ǦȽǡ ǦͳȾǡ Ǧ͸ ƒ†  ʹ ™‡”‡ †‡–‡”‹‡† „› —•‹‰ –Š‡ …‘‡”…‹ƒŽŽ› ƒ˜ƒ‹Žƒ„Ž‡‹–ƒ……‘”†‹‰–‘–Š‡ƒ—ˆƒ…–—”‡”ǯ•‹•–”—…–‹‘•ǤŠ‡˜ƒŽ—‡™ƒ•†‡–‡”‹‡†ƒ–ͶͷͲ —•‹‰ ƒ ƒ”‹‘•ƒ  —Ž–‹‘†‡ ‹…”‘’Žƒ–‡ ‡ƒ†‡” ȋŠ‡”‘ ‹•Š‡” …‹‡–‹ϐ‹… …Ǥ ƒŽ–Šƒǡ ǡ Ȍ and calculated at the linear portion of the curve Serum cytokines levels were measured using commercial ‡œ›‡Ž‹‡†‹—‘•‘”„‡–ƒ••ƒ›‹–ǡ ǦȾͳǡ ǦȽǡǦͳȾǡǦ͸ˆ”‘‘‰‡ȋ‹••‹••ƒ—‰ƒǡ–ƒ”‹‘ǡ ƒƒ†ƒȌ ƒ†  ʹ ˆ”‘ Ƭ ›•–‡• …Ǥ ȋ‹‡ƒ’‘Ž‹•ǡ ǡ Ȍ ƒ……‘”†‹‰ –‘ –Š‡ ƒ—ˆƒ…–—”‡”ǯ• instructions Western blot analysis ”‘œ‡Ž—‰•™‡”‡’—Ž˜‡”‹œ‡†‹ƒ‹••—‡Ž›•‡”ƒ†Ž›•‡†‹„—ˆˆ‡”ȋŠ‡”‘ ‹•Š‡”…‹‡–‹ϐ‹……Ǥ ƒŽ–ŠƒǡǡȌǤŠ‡–Š‡Ž›•ƒ–‡•™‡”‡…‡–”‹ˆ—‰‡†ƒ–ͳʹǡͲͲͲ‰ƒ–Ͷιˆ‘”ͳͷ‹ǡƒ†–Š‡•—’‡”ƒ–ƒ–• ™‡”‡ …‘ŽŽ‡…–‡† ˆ‘” –‘–ƒŽ ’”‘–‡‹ …‘…‡–”ƒ–‹‘ ƒƒŽ›•‹• „› ƒ  ’”‘–‡‹ ƒ••ƒ› ‹– ȋ‡›‘–‹‡ •–‹–—–‡ ‘ˆ ‹‘–‡…Š‘Ž‘‰›ǡ ƒ–‘‰ǡ Š‹ƒȌǤ “—ƒŽ ƒ‘—–• ‘ˆ ’”‘–‡‹ ™‡”‡ •‡’ƒ”ƒ–‡† „› Ǧ ǡ –”ƒ•ˆ‡””‡† –‘  ‡„”ƒ‡ȋ‹ŽŽ‹’‘”‡‘”’Ǥǡ‹ŽŽ‡”‹…ƒǡǡȌǡƒ†‹…—„ƒ–‡†™‹–ŠͷΨ•‹‹Žȋ‡…–‘ǡ‹…‹•‘ ƒ†‘’ƒ›ǡ ”ƒŽ‹Žƒ‡ǡ‡™ ‡”•‡›ǡȌƒ–”‘‘–‡’‡”ƒ–—”‡ˆ‘”ͳǤͷŠ–‘„Ž‘…‘Ǧ•’‡…‹ϐ‹…„‹†‹‰Ǥ Š‡‡„”ƒ‡•™‡”‡–Š‡‹…—„ƒ–‡†™‹–Š–Š‡ˆ‘ŽŽ‘™‹‰’”‹ƒ”›ƒ–‹„‘†‹‡•ƒ–”‘‘–‡’‡”ƒ–—”‡ˆ‘”ʹŠ ‘”Ͷι‘˜‡”‹‰Š–ǣȋͳǣͳͲͲͲȌǡ’ǦȋͳǣͳͲͲͲȌǡ™‡”‡‘„–ƒ‹‡†ˆ”‘‡ŽŽ‹‰ƒŽ‹‰‡…Š‘Ž‘‰›ȋǡȌǢ ʹȋͳǣͳͲͲͲȌǡ ͻ ȋͳǣͳͲͲͲȌ ™‡”‡ ‘„–ƒ‹‡† ˆ”‘ „…ƒ ȋǡ Ȍǡ Ǧ…ƒ†Š‡”‹ ȋͳǣͳͲͲͲȌ ‘” ȾǦƒ…–‹ ȋͳǣʹͲͲͲǢ ‡ŽŽ ‹‰ƒŽ‹‰ ‡…Š‘Ž‘‰›ǡ …Ǥǡ ƒ˜‡”•ǡ ǡ ȌǤ ˆ–‡” ™ƒ•Š‹‰ ™‹–Š Ǧǡ –Š‡ ‡„”ƒ‡• ™‡”‡ ‹…—„ƒ–‡† ™‹–Š Ǧ…‘Œ—‰ƒ–‡† •‡…‘†ƒ”› ƒ–‹„‘†‹‡• ȋŠƒ‰Šƒ‹ ‹‘–‡…Š‘Ž‘‰›ǡ Šƒ‰Šƒ‹ǡ Š‹ƒȌǤ Š‡’”‘–‡‹„ƒ†•™‡”‡˜‹•—ƒŽ‹œ‡†—•‹‰‡Šƒ…‡†…Š‡‹Ž—‹‡•…‡…‡™‹–Šƒ—’‡”‹‰ƒŽ™‡•–’‹…‘‹– ȋ”‹†‰‡‹‘Ž‘‰‹…ƒŽ‡…Š‘Ž‘‰›ǡŠƒ‰Šƒ‹ǡŠ‹ƒȌǤ ‹Ž•™‡”‡•…ƒ‡†ƒ†ƒƒŽ›œ‡†„›†‡•‹–‘‡–”›—•‹‰ ›‰‡‡ ‡‡ ‡‹—••‘ˆ–™ƒ”‡ȋ›‰‡‡ǡ ”‡†‡”‹…ǡǡȌǤ RNA isolation and reverse transcription reaction ‘–ƒŽ  ™ƒ• ‡š–”ƒ…–‡† ˆ”‘ –Š‡ ˆ”‘œ‡ Ž—‰• –‹••—‡ •ƒ’Ž‡• ȋͷͲ Ǧ ͺͲ ‰Ȍ —•‹‰ œ‘Ž ”‡ƒ‰‡– ȋ˜‹–”‘‰‡ǡƒ”Ž•„ƒ†ǡȌƒ……‘”†‹‰–‘–Š‡ƒ—ˆƒ…–—”‡”̵•’”‘–‘…‘ŽǤ‘–ƒŽˆ”‘‡ƒ…Š•ƒ’Ž‡™ƒ• “—ƒ–‹ϐ‹‡†—•‹‰ƒ‹…”‘˜‘Ž—‡•’‡…–”‘‡–‡”Ǥ ”‹‡ϐŽ›ǡ–Š‡ƒ“—‡‘—•’Šƒ•‡™ƒ•—•‡†ˆ‘”’”‡…‹’‹–ƒ–‹‘™‹–Šƒ‡“—ƒŽ˜‘Ž—‡‘ˆ‹•‘’”‘’ƒ‘ŽǤŠ‡ ’‡ŽŽ‡–™ƒ•™ƒ•Š‡†‘…‡™‹–ŠͺͲͲɊ͹ͷΨ‡–Šƒ‘Ž–Š‡ƒ‹”Ǧ†”‹‡†ƒ††‹••‘Ž˜‡†‹ͷͲɊƒ•‡ˆ”‡‡ ™ƒ–‡”Ǥ  ™ƒ• “—ƒ–‹ϐ‹‡† „› —•‹‰ ƒ •’‡…–”‘’Š‘–‘‡–‡” ȋ‘Ž‡…—Žƒ” ‡˜‹…‡•ǡ Ȍǡ ƒ† –Š‡ “—ƒŽ‹–› ™ƒ• …Š‡…‡† „› ƒ‰ƒ”‘•‡ ‰‡Ž ‡Ž‡…–”‘’Š‘”‡•‹•Ǥ Š‡ ”‡˜‡”•‡ –”ƒ•…”‹’–‹‘ ȋȌ ”‡ƒ…–‹‘ ™ƒ• …ƒ””‹‡† ‘—– —•‹‰ ‡˜‡””ƒ…‡“ƒ•–‡”‹š™‹–Š‰‡‘˜‡”ȋ‘†‡‘Ǥ Ǧ͵ͲͳȌȋ‘›‘„‘‘Ǥ–†Ǥǡ•ƒƒǡ ƒ’ƒȌ ƒ……‘”†‹‰–‘–Š‡ƒ—ˆƒ…–—”‡”̵•‹•–”—…–‹‘•ƒ†–Š‡…’”‘†—…–™ƒ••–‘”‡†ƒ–ǦʹͲι‘”—•‡†‹‡†‹ƒ–‡Ž› for realtime PCR Quantitative real-time polymerase chain reaction (qPCR) ‡ —•‡† ”‡ƒŽǦ–‹‡ “—ƒ–‹–ƒ–‡†  –‘ ‡ƒ•—”‡ –Š‡ ‡š’”‡••‹‘ ‘ˆ –Š‡ Ž—‰  Ž‡˜‡Ž•ǡ —ƒ–‹–ƒ–‹˜‡ ”‡ƒŽǦ–‹‡‘Ž›‡”ƒ•‡Šƒ‹‡ƒ…–‹‘ȋ“Ȍ™ƒ•’‡”ˆ‘”‡†„›—•‹‰ ”‡‡”‡ƒŽ–‹‡ƒ•–‡” ‹šǡǦʹͲͳȋ‘›‘„‘‘Ǥ–†Ǥǡ•ƒƒǡ ƒ’ƒȌǤŠ‡ʹͲɊ•–ƒ†ƒ”†”‡ƒ…–‹‘…‘–ƒ‹‹‰ͲǤͺɊ‘ˆ‡ƒ…Š ’”‹‡” ȋϐ‹ƒŽ …‘…‡–”ƒ–‹‘ ͲǤͶ ɊȌǡ ͳͲ — ‘ˆ  ”‡‡ǡ ʹ Ɋ ‘ˆ … ƒ† ͸ǤͶ Ɋ ƒ•‡ ˆ”‡‡ ™ƒ–‡”Ǥ ’Ž‹ϐ‹…ƒ–‹‘ƒ††‡–‡…–‹‘™‡”‡’‡”ˆ‘”‡†‹ƒ‹‰Š–›…Ž‡”ͶͺͲȋ‘…Š‡‹ƒ‰‘•–‹…•ǡ‡œ„‡”‰ǡ ‡”ƒ›Ȍǡ Downloaded by: Univ of California San Diego 132.239.1.231 - 3/3/2017 8:59:18 AM Table PCR Primers Physiol Biochem 2016;38:619-634 Cellular Physiology Cell © 2016 The Author(s) Published by S Karger AG, Basel DOI: 10.1159/000438655 and Biochemistry Published online: February 08, 2016 www.karger.com/cpb 623 Zhao et al.: Myrtol Standardized on Radiation-Induced Lung Injury ’”‹‡”•—•‡†‹–Š‹••–—†›ȋƒ„Ž‡ͳȌ™‡”‡•›–Š‡•‹•‡†„›—Šƒ ‡‡”‡ƒ–‡‹‘Ž‘‰‹…ƒŽ‰‹‡‡”‹‰‘Ǥǡ –†ǤǤŠ‡”‡ƒ…–‹‘•™‡”‡‹…—„ƒ–‡†‹ƒ͵ʹǦ™‡ŽŽ’Žƒ–‡ƒ–ͻͷιˆ‘”ͳͲ‹ǡˆ‘ŽŽ‘™‡†„›ͶͲ…›…Ž‡•‘ˆͻͷιˆ‘”ͷ•ǡ ͷͷιˆ‘”ͳͲ•ƒ†͹ʹιˆ‘”ͳͷ•ȋ†ƒ–ƒ…‘ŽŽ‡…–‹‘ȌǤ ™ƒ•—•‡†ƒ•ƒ”‡ˆ‡”‡…‡ˆ‘”‘”ƒŽ‹œƒ–‹‘Ǥ Statistical analysis ƒ–ƒ ™‡”‡ ‡š’”‡••‡† ƒ• –Š‡ ‡ƒ• ά •–ƒ†ƒ”† †‡˜‹ƒ–‹‘• ȋ•ȌǤ ‡–™‡‡ ‰”‘—’ †‹ˆˆ‡”‡…‡• ™‡”‡ –‡•–‡†—•‹‰ƒ‘‡Ǧ™ƒ›Ǥ™‘Ǧ‰”‘—’…‘’ƒ”‹•‘•™‡”‡’‡”ˆ‘”‡†„›—•‹‰‹†‡’‡†‡–Ǧ•ƒ’Ž‡• –—†‡–ǯ•–Ǧ–‡•–•Ǥ’δͲǤͲͷ™ƒ•…‘•‹†‡”‡†•‹‰‹ϐ‹…ƒ–Ǥ Results Myrtol rescued body weight decrease caused by irradiation Š‡ „‘†› ™‡‹‰Š– ‰ƒ‹ ‹ ‹…‡ ˆ”‘ …‘–”‘Ž ‰”‘—’ ‹…”‡ƒ•‡† ™‹–Š –‹‡Ǥ ‘™‡˜‡”ǡ –Š‡ ’”‡†‹•‘‡Ǧ–”‡ƒ–‡†‰”‘—’ƒ†”ƒ†‹ƒ–‹‘‘Ž›‰”‘—’™‡”‡Ž‘™‡”–Šƒ–Š‡…‘–”‘Ž‰”‘—’ƒ–ʹǡ Ͷƒ†ͺ™‡‡•’‘•–Ǧ‹””ƒ†‹ƒ–‹‘Ǥ—––Š‡›”–‘Ž–”‡ƒ–‡–•‹‰‹ϐ‹…ƒ–Ž›ȋ’δͲǤͲͷǡ’δͲǤͲͳȌ ”‡•…—‡† –Š‡ „‘†› ™‡‹‰Š– Ž‘•• …ƒ—•‡† „› ‹””ƒ†‹ƒ–‹‘Ǥ ˜‡ ƒ– ͳ͸ ™‡‡• ’‘•–Ǧ‹””ƒ†‹ƒ–‹‘ǡ „‘†›™‡‹‰Š–Ž‘••‹’”‡†‹•‘‡ƒ†”ƒ†‹ƒ–‹‘‘Ž›‰”‘—’ǡ™ƒ••–‹ŽŽŽ‘™‡”–Šƒ›”–‘Ž‰”‘—’ ȋ ‹‰ǤͳȌǤ ›”–‘Ž”‡†—…‡†„Ž‡‡†‹‰•‹–‡•ƒ†Ž—‰…‘‡ˆϔ‹…‹‡– —‰ „Ž‡‡†‹‰ •‹–‡• ƒ† ‡†‡ƒ ‹ ›”–‘Ž –”‡ƒ–‡† ‹…‡ ™‡”‡ ƒ––‡—ƒ–‡† …‘’ƒ”‡† ™‹–Š radiation ‘Ž›ƒ‹ƒŽ•ƒ–ͺ™‡‡•’‘•–Ǧ‹””ƒ†‹ƒ–‹‘ȋ ‹‰ǤʹȌǤ—–”‡†‹•‘‡…ƒ‘Ž›”‡†—…‡ –Š‡•‡˜‡”‹–›‘ˆƒ…—–‡‹ϐŽƒƒ–‹‘‹ϐ‹”•––™‘™‡‡•Ǥƒ††‹–‹‘ǡ™‡ƒŽ•‘ˆ‘—†–Šƒ––Š‡ Fig 2. —‰ ƒ’’‡”ƒ…‡ ƒ† Ž—‰ …‘‡ˆϐ‹…‹‡–Ǥǣˆˆ‡…–‘ˆ›”–‘Ž •–ƒdardized on the lung appearance ƒ– ͺ ™‡‡• ’‘•– ‰ƒƒǦ”ƒ› ‹””ƒ†‹ƒ–‹‘ ȋȌ —‰ –‹••—‡ ˆ”‘ ‘”ƒŽ …‘–”‘ŽȋȌ—–”‡ƒ–‡†‹””ƒ†‹ƒ–‡†ȋȌ ›”–‘ŽǦ–”‡ƒ–‡† ‹””ƒ†‹ƒ–‡† ȋȌ ’”‡†‹•‘‡Ǧ–”‡ƒ–‡† ‹””ƒ†‹ƒ–‡†Ǥ ƒ” α ͳ…Ǥ ǣ  „ƒ” ‰”ƒ’Š ‘ˆ Ž—‰ …‘‡ˆϐ‹…‹‡– ȋŽ—‰ ™‡‹‰Š–Ȁ„™Ȍ ˆ”‘ †‹ˆˆ‡”‡– ‰”‘—’•Ǥ ƒ–ƒ ™‡”‡ ‡š’”‡••‡† ƒ•–Š‡‡ƒ•ά•–ƒ†ƒ”††‡˜‹ƒ–‹‘• ȋ•Ȍ ȋ α ͸ǡ ȗ ’ δ ͲǤͲͷ ƒ† ȗȗ ’ δ ͲǤͲͳǡ˜•ǤΪ›”–‘ŽȌǤ Downloaded by: Univ of California San Diego 132.239.1.231 - 3/3/2017 8:59:18 AM Fig 1. ‹…‡ „‘†› ™‡‹‰Š– ƒŽ–‡”ƒ–‹‘ ˆ”‘†‹ˆˆ‡”‡–‰”‘—’•Ǥ˜‡”ƒ‰‡„‘†› weight of mice in different group ™‡”‡ ”‡…‘”†‡† ƒ– Ͳǡ ͳǡ ʹǡ ͵ Ͷǡ ͺ ƒ† ͳ͸ ™‡‡• ’‘•– ”ƒ†‹ƒ–‹‘Ǥ ƒ–ƒ ™‡”‡ ‡š’”‡••‡† ƒ• –Š‡ ‡ƒ• ά •–ƒ†ƒ”† †‡˜‹ƒ–‹‘•ȋ•Ȍȋα͸Ǥȗ’δͲǤͲͷǡȗȗ ’δͲǤͲͳǡ˜•ǤΪ›”–‘ŽȌǤ Physiol Biochem 2016;38:619-634 Cellular Physiology Cell © 2016 The Author(s) Published by S Karger AG, Basel DOI: 10.1159/000438655 and Biochemistry Published online: February 08, 2016 www.karger.com/cpb 624 Zhao et al.: Myrtol Standardized on Radiation-Induced Lung Injury Fig 3. ‹•–‘’ƒ–Š‘Ž‘‰‹…ƒŽ ϐ‹†‹‰• ‘ˆ ’—Ž‘ƒ”› ‹ϐŽƒƒ–‹‘ ƒ† ϐ‹„”‘•‹•Ǥ ȋȌ ”‡’”‡•‡–ƒ–‹˜‡ ‹ƒ‰‡• ‘ˆ Ƭ•–ƒ‹‹‰‘ˆŽ—‰–‹••—‡•‘ˆ‹…‡ˆ”‘†‹ˆˆ‡”‡–‰”‘—’•ƒ–ͳǡʹǡͶǡͺǡͳ͸™‡‡•’‘•–Ǧ‹””ƒ†‹ƒ–‹‘Ǥƒ”αʹͲ ɊǤȋȌ•Š…”‘ˆ–•…‘”‡•‡‹“—ƒ–‹–ƒ–‹˜‡Š‹•–‘Ž‘‰‹…ƒŽƒƒŽ›•‹•‘ˆ’—Ž‘ƒ”›‹Œ—”›ƒ†ϐ‹„”‘•‹•ˆ‘”†‹ˆˆ‡”‡– ‰”‘—’•ȋα͸ǡȗ’δͲǤͲͷƒ†ȗȗ’δͲǤͲͳ˜•ǤȌǤȋȌƒ••‘ǯ•–”‹…Š”‘‡ˆ”‘‹…‡‹–Š‡‘”ƒŽ‘Ǧ‹””ƒ†‹ƒ–‡†ȋȌǡ‹””ƒ†‹ƒ–‡†‘Ž›ȋȌǡ’”‡†‹•‘‡Ǧ–”‡ƒ–‡†ȋΪȌǡƒ†›”–‘ŽǦ–”‡ƒ–‡†ȋΪȌ ‰”‘—’•Ǥƒ”αʹͲɊǤȋȌ—ƒ–‹ϐ‹…ƒ–‹‘‘ˆƒ••‘ǯ•”‹…Š”‘‡ˆ‘”…‘ŽŽƒ‰‡…‘–‡–ˆ‘”†‹ˆˆ‡”‡–‰”‘—’•Ǥ ƒ–ƒ™‡”‡‡š’”‡••‡†ƒ•–Š‡‡ƒ•ά•–ƒ†ƒ”††‡˜‹ƒ–‹‘•ȋ•Ȍȋα͸ǡȗ’δͲǤͲͷƒ†ȗȗ’δͲǤͲͳ˜•ǤȌǤ ˆˆ‡…–•‘ˆ›”–‘Ž‘’—Ž‘ƒ”›‹ϔŽƒƒ–‹‘ƒ†…‘ŽŽƒ‰‡ϔ‹„‡”•‹˜‹˜‘ ‡‡šƒ‹‡†™Š‡–Š‡”›”–‘Ž–”‡ƒ–‡–…‘—Ž†‡š‡”–ƒ–‹Ǧ‹ϐŽƒƒ–‘”›ƒ†ƒ–‹Ǧϐ‹„”‘–‹… ‡ˆˆ‡…– ‹ ”ƒ†‹ƒ–‹‘Ǧ‹†—…‡† Ž—‰ ‹Œ—”›Ǥ ‡ ’‡”ˆ‘”‡† Ƭ •–ƒ‹‡† ƒ† ƒ••‘Ǧ•–ƒ‹‡† ƒ••ƒ›•ƒ†‘„•‡”˜‡†ƒ…”‘’Šƒ‰‡•‹ϐ‹Ž–”ƒ–‹‘‹’—Ž‘ƒ”›ƒŽ˜‡‘Ž‹ƒ†ϐ‹„”‘•‹•ˆ‘”ƒ–‹‘ ‹ Žƒ––‡” ’Šƒ•‡ ȋ ‹‰Ǥ ͵ ƒ† ȌǤ ‡˜‡”‡ ‹–‡”•–‹–‹ƒŽ ’—Ž‘ƒ”› ‡†‡ƒ ƒ† ƒ…”‘’Šƒ‰‡ ƒ……——Žƒ–‹‘™‡”‡‘„˜‡”•‡†‹’—Ž‘ƒ”›ˆ”‘‹””ƒ†‹ƒ–‡†‰”‘—’ǤŠ‡ƒŽ˜‡‘Ž‹–‹•ƒ†ϐ‹„”‘•‹• ™‡”‡ •‹‰‹ϐ‹…ƒ–Ž› ”‡†—…‡† ‹ ›”–‘Ž ‰”‘—’• ȋ’ δ ͲǤͲͷǡ ’ δ ͲǤͲͳȌ ȋ ‹‰Ǥ ͵ȌǤ ‡ …‘ϐ‹”‡† –Šƒ– ‹””ƒ†‹ƒ–‡† ‹…‡ Šƒ† ƒ”‡† ϐ‹„”‘–‹… …Šƒ‰‡• ‹ ƒŽ˜‡‘Žƒ” ƒ”‡ƒ•ǡ „—– ‹””ƒ†‹ƒ–‡† ƒ‹ƒŽ –”‡ƒ–‡†™‹–Š›”–‘Ž•Š‘™‡†–Šƒ–•‹‰‹ϐ‹…ƒ–Ž›Ž‡••†ƒƒ‰‡ǡƒ•‡˜‹†‡…‡†„›ƒ••‘Ǧ•–ƒ‹‡† •‡…–‹‘•„Ž—‡•–ƒ‹‹‰”ƒ–‡ȋ’δͲǤͲͷǡ’δͲǤͲͳȌȋ ‹‰Ǥ͵ȌǤ‘”’Š‘Ž‘‰‹…ƒŽ‘„•‡”˜ƒ–‹‘—†‡” ‹˜‡”–‡†‹…”‘•…‘’‡ǡ™‡ˆ‘—†–Šƒ–ƒŽ˜‡‘Žƒ”™ƒŽŽ•˜‹•‹„Ž‡–Š‹…‡‡†ǡƒŽ˜‡‘Ž‹…‘ŽŽƒ’•‡†ǡˆ‘ƒ Downloaded by: Univ of California San Diego 132.239.1.231 - 3/3/2017 8:59:18 AM Ž—‰…‘‡ˆϐ‹…‹‡–™ƒ••‹‰‹ϐ‹…ƒ–Ž›Ž‘™‡”ȋ’δͲǤͲͷǡ’δͲǤͲͳȌ‹›”–‘Ž–”‡ƒ–‡†‹…‡”‡Žƒ–‹˜‡–‘ ”ƒ†‹ƒ–‹‘‘Ž›‹…‡ƒ–ͳǡʹǡͶǡͺƒ†ͳ͸™‡‡•’‘•–Ǧ‹””ƒ†‹ƒ–‹‘ȋ ‹‰ǤʹȌǤŠ‹•”‡•—Ž–…‘””‡Žƒ–‡• ™‹–Š–Š‡’—Ž‘ƒ”›’ƒ–Š‘Ž‘‰‹…ƒŽƒ’’‡ƒ”ƒ…‡‹›”–‘Ž–”‡ƒ–‡†ƒ‹ƒŽ•ƒ–†‹ˆˆ‡”‡––‹‡•’‘•–Ǧ ‹””ƒ†‹ƒ–‹‘ȋ ‹‰Ǥ͵ƒ†ȌǤŠ‡•‡”‡•—Ž–•‹†‹…ƒ–‡†–Šƒ–›”–‘Žƒ––‡—ƒ–‡†’‡—‘‡†‡ƒ post-irradiation Physiol Biochem 2016;38:619-634 Cellular Physiology Cell © 2016 The Author(s) Published by S Karger AG, Basel DOI: 10.1159/000438655 and Biochemistry Published online: February 08, 2016 www.karger.com/cpb 625 Zhao et al.: Myrtol Standardized on Radiation-Induced Lung Injury Fig 4.Š‡‡ˆˆ‡…–•‘ˆ›–”‘Ž‘ƒ”‡”•‹Ž—‰ –‹••—‡•ˆ”‘†‹ˆˆ‡”‡– ‰”‘—’•Ǥ—‘ϐŽ—‘”‡•…‡…‡ •Š‘™• –Š‡ ‡š’”‡••‹‘• ‘ˆ ˜‹‡–‹ ƒ† ȽǦ ‹ ‹…‡ ’—Ž‘ƒ”› ȋέ ʹͲͲȌǤ ‘–‡•ǣ ˜‹‡–‹ ȋ‰”‡‡Ȍǡ ȽǦȋ”‡†Ȍƒ†…‡ŽŽ—…Ž‡—•ȋ„Ž—‡ȌǤȋȌ˜‹‡–‹ǡͺ ™‡‡• ’‘•–Ǧ”ƒ†‹ƒ–‹‘Ǥ ȋȌ ȽǦǡ ͺ ™‡‡• ’‘•–Ǧ”ƒdiation (C) vimentin, 16 weeks post-radiation ȋȌ ȽǦǡ ͳ͸ ™‡‡• ’‘•–Ǧ”ƒ†‹ƒ–‹‘Ǥ  •–ƒ‹‹‰ ȋ„Ž—‡Ȍ™ƒ•—•‡†–‘˜‹•—ƒŽ‹œ‡–Š‡—…Ž‡‹ȋέʹͲͲƒ‰‹ϐ‹…ƒ–‹‘ȌǤƒ”ǡͳͲͲɊǤȋȌǦ…ƒ†Š‡”‹‡š’”‡••‹‘ǡͺ and 16 weeks post-radiation Effects of Myrtol on mesenchymal markers in vivo ƒ†‹ƒ–‹‘ ‹†—…‡†  ‹• ‘™ –‘ ’”‘‘–‡ –Š‡ ’”‘…‡••‡• ‘ˆ ϐ‹„”‘•‹•Ǥ ‘ ™‡ ‡šƒ‹‡† –Š‡ …Šƒ‰‡• ‘ˆ ‡’‹–Š‡Ž‹ƒŽ ƒ”‡”ǡ Ǧ…ƒ†Š‡”‹ǡ ‡•‡…Š›ƒŽ ƒ‡”•ǡ ˜‹‡–‹ ƒ† ȽǦ ȋ ‹‰Ǥ ͶȌǤ —‘ϐŽ—‘”‡•…‡…‡ •–ƒ‹‹‰ ‹†‡–‹ϐ‹‡† ˆ‡™ ȽǦ ƒ† ˜‹‡–‹ ’‘•‹–‹˜‡ …‡ŽŽ• ‹ –Š‡ Ž—‰ ‘ˆ ›”–‘ŽǦ–”‡ƒ–‡† ‹…‡ ƒ– ͺ ƒ† ͳ͸ ™‡‡• ’‘•–Ǧ”ƒ†‹ƒ–‹‘Ǥ  …‘–”ƒ•–ǡ •–”‘‰ ˜‹‡–‹ ƒ† ȽǦ staining was detected in the pulmonary arterioles of irradiation only and prednisone group in lung tissue Similarly, we found –Šƒ–Ǧ…ƒ†Š‡”‹‡š’”‡••‹‘™ƒ•—’”‡‰—Žƒ–‡† ‹ –Š‡ Ž—‰• ‘ˆ ›”–‘ŽǦ–”‡ƒ–‡† ƒ‹ƒŽ• ƒ– ͺ and 16weeks post-radiation These results Downloaded by: Univ of California San Diego 132.239.1.231 - 3/3/2017 8:59:18 AM …‡ŽŽ• ƒ”‘—† –Š‡ „”‘…Š‹‘Ž‡ ƒ† ƒ Žƒ”‰‡ ‘ˆ —„‡” ‘ˆ •ƒŽŽ ƒ‹”™ƒ› ‹ϐŽƒƒ–‘”› …‡ŽŽ ‹ϐ‹Ž–”ƒ–‹‘Ǥš–‡•‹˜‡†‡’‘•‹–‹‘•‘ˆ…‘ŽŽƒ‰‡ ƒ†”‡‰‹‘ƒŽϐ‹„”‘–‹…ˆ‘…‹™‡”‡ƒŽ•‘‘„•‡”˜‡† ‹ –Š‡ ƬǦ•–ƒ‹‡† ƒ† ƒ••‘Ǧ•–ƒ‹‡† ‹””ƒ†‹ƒ–‡†’—Ž‘ƒ”›–‹••—‡•ƒ– Ͷǡͺƒ†ͳ͸ weeks post-irradiation ‡ƒŽ•‘‡šƒ‹‡†–Š‡…‘–‡–‘ˆ›’‹ Ž—‰ –‹••—‡ ȋ ‹‰Ǥ ͸ Ȍǡ –Š‡ ƒŒ‘” …‘•–‹–—‡– of collagen, from lung tissues The results •Š‘™‡† –Šƒ– Ž‡•• ›’ ™ƒ• ˆ‘—† ‹ ›”–‘ŽǦ treated animals than in the irradiation only ‰”‘—’ƒ†’”‡†‹•‘‡‰”‘—’Ǥ–Š‡ϐ‹”•––™‘ ™‡‡• –Š‡”‡ ™ƒ• ‘ •‹‰‹ϐ‹…ƒ– ›’ …Šƒ‰‡ ‘„•‡”˜‡†‹›”–‘ŽǦ–”‡ƒ–‡†‰”‘—’…‘’ƒ”‡† to controls However, the amount of Hyp ‹…”‡ƒ•‡† ‹ ͺ ™‡‡• ƒ† ͳ͸ ™‡‡• ‹ –Š‡ irradiation groups The Hyp content was •‹‰‹ϐ‹…ƒ–Ž› Ž‘™‡” ȋ’ δ ͲǤͲͷǡ ’ δ ͲǤͲͳȌ ‹ ›”–‘ŽǦ–”‡ƒ–‡†ƒ‹ƒŽ•–Šƒ‹”ƒ†‹ƒ–‹‘‘Ž› ‰”‘—’ ƒ– ͺ ƒ† ͳ͸ ™‡‡• ’‘•–Ǧ‹””ƒ†‹ƒ–‹‘Ǥ Taken together, these results showed marked ƒ–‹Ǧ‹ϐŽƒƒ–‘”›ƒ†ƒ–‹Ǧϐ‹„”‘–‹…‡ˆˆ‡…–•‘ˆ ›”–‘Ž in vivo Physiol Biochem 2016;38:619-634 Cellular Physiology Cell © 2016 The Author(s) Published by S Karger AG, Basel DOI: 10.1159/000438655 and Biochemistry Published online: February 08, 2016 www.karger.com/cpb 626 Zhao et al.: Myrtol Standardized on Radiation-Induced Lung Injury Fig 5.ˆˆ‡…–•‘ˆ›”–‘Ž‘–Š‡ƒ…–‹˜‹–‹‡•‘ˆ  ƒ† ‘ –Š‡  …‘–‡– ‹ –Š‡ Ž—‰ –‹••—‡ǤȋȌˆˆ‡…–‘ˆ›”–‘Ž‘‹…‡’—Ž‘ƒ”›…‘–‡–ȋȌƒ…–‹˜‹–›ƒ–ͳǡʹǡ Ͷǡ ͺ ƒ† ͳ͸ ™‡‡• ’‘•–Ǧ‹””ƒ†‹ƒ–‹‘Ǥ ƒ–ƒ ™‡”‡’”‡•‡–‡†ƒ•‡ƒάȋα͸ǡȗδ ͲǤͲͷǡȗȗδͲǤͲͳ˜•ǤΪȌǤ ‹†‹…ƒ–‡†–Šƒ–›”–‘Ž–”‡ƒ–‡–…‘—Ž†‹Š‹„‹––Š‡’”‘…‡••‘ˆǡ™Š‹…Š‹‰Š–ƒ……‘—–ˆ‘” •‘‡’‘••‹„Ž‡‡…Šƒ‹•Ǥ Myrtol modulates the lung tissue MDA content and SOD activity —‰–‹••—‡…‘–‡–ƒ†ƒ…–‹˜‹–›™‡”‡‡ƒ•—”‡†–‘ƒ••‡••–Š‡‘š‹†ƒ–‹˜‡ƒ† ƒ–‹‘š‹†ƒ– •–ƒ–—•‡•ǡ ”‡•’‡…–‹˜‡Ž›Ǥ Š‡  …‘–‡– ‘ˆ Ž—‰ –‹••—‡ ‹””ƒ†‹ƒ–‹‘ ‘Ž› ‰”‘—’ †”ƒƒ–‹…ƒŽŽ›‹…”‡ƒ•‡†ǡ™Š‹…Š™ƒ•‹Š‹„‹–‡†„››”–‘Ž–”‡ƒ–‡–ȋ’δͲǤͲͷǡ’δͲǤͲͳȌȋ ‹‰Ǥ ͷȌǤ‡ƒŽ•‘†‡–‡…–‡†–Š‡Ž—‰ƒ…–‹˜‹–›ǡƒ‹†‹…ƒ–‘”‘ˆƒ–‹‘š‹†ƒ–…ƒ’ƒ…‹–›ǡƒ–ͳǡͶǡͺƒ† ͳ͸™‡‡•ƒˆ–‡”‹””ƒ†‹ƒ–‹‘ȋ ‹‰ǤͷȌǡƒ…–‹˜‹–›™ƒ••‹‰‹ϐ‹…ƒ–Ž›Š‹‰Š‡”ȋ’δͲǤͲͷǡ’δͲǤͲͳȌ ‹›”–‘ŽǦ–”‡ƒ–‡†ƒ‹ƒŽ•…‘’ƒ”‡†™‹–Šƒ‹ƒŽ•‹”ƒ†‹ƒ–‹‘‘Ž›‰”‘—’ƒ–ͳǡʹǡͶǡͺƒ†ͳ͸ ™‡‡•’‘•–Ǧ‹””ƒ†‹ƒ–‹‘Ǥƒ…–‹˜‹–›‹–Š‡’”‡†‹•‘‡‰”‘—’™ƒ••‹‹Žƒ”™‹–Š‹””ƒ†‹ƒ–‹‘ ‹…‡ƒ–Ͷǡͺƒ†ͳ͸™‡‡•’‘•–Ǧ‹””ƒ†‹ƒ–‹‘ǤŠ‡•‡†ƒ–ƒ†‡‘•–”ƒ–‡†–Šƒ–›”–‘Ž…‘—Ž†”‡Ž‹‡ˆ ‘š‹†ƒ–‹˜‡†ƒƒ‰‡in vivo Effects of Myrtol on matrix metalloproteinases expression and Akt phosphorylation •‹‰ƒŽ‹‰’ƒ–Š™ƒ›’Žƒ›•ƒ…”‹–‹…ƒŽ”‘Ž‡‹”ƒ†‹ƒ–‹‘‹†—…‡†Ž—‰‹Œ—”›ȏͳͻȐǤ—”†ƒ–ƒ showed that the phosphorylation of AKT increased in the lung of irradiated mice compared ™‹–Š‹…‡‹…‘–”‘Ž‰”‘—’ǡƒ†›”–‘Ž‹Š‹„‹–‡†–Š‡’Š‘•’Š‘”›Žƒ–‹‘‘ˆ‹Ž—‰Ž‡˜‡Ž ‹‹””ƒ†‹ƒ–‡†‹…‡Ǥ›”–‘Žƒ†‹‹•–”ƒ–‹‘‹Š‹„‹–‡†Ǧʹ‡š’”‡••‹‘ƒ††‘™Ǧ”‡‰—Žƒ–‡† Downloaded by: Univ of California San Diego 132.239.1.231 - 3/3/2017 8:59:18 AM Myrtol regulates serum cytokine levels and mRNA expression levels • †‡’‹…–‡† ‹ ‹‰. ͸ǡ ™‡ ˆ‘—† –Šƒ– –Š‡ Ž‡˜‡Ž ‘ˆ „‘–Š ’”‘‹ϐŽƒƒ–‘”› …›–‘‹‡• ȋ ǦȽǡǦͳȾǡǦ͸ƒ† ʹȌƒ† ǦȾͳ‹–Š‡•‡”—™‡”‡‹…”‡ƒ•‡†ƒ–ʹǡͶǡͺǡͳ͸™‡‡• ‹ ‹””ƒ†‹ƒ–‹‘ ‘Ž› ‰”‘—’Ǥ Š‡ ›”–‘Ž –”‡ƒ–‡– •‹‰‹ϐ‹…ƒ–Ž› ȋ’ δ ͲǤͲͷǡ ’ δ ͲǤͲͳȌ †‘™”‡‰—Žƒ–‡†–Š‡Ž‡˜‡Ž•‘ˆ’”‘‹ϐŽƒƒ–‘”›…›–‘‹‡•ȋ ǦȽ,ǦͳȾǡǦ͸ƒ† ʹȌƒ† ǦȾͳǤ –‡”‡•–‹‰Ž›ǡ ʹ‹Žƒ––‡”•–ƒ‰‡•–‹ŽŽ‡’–Š‹‰Š‡”Ž‡˜‡Ž•–Šƒ–Šƒ–‹‘–Š‡”‰”‘—’•ǡ‹†‹…ƒ–‹‰ ƒ ”‘Ž‡ ‹ ’”‡˜‡–‹‰ ”ƒ†‹ƒ–‹‘Ǧ‹†—…‡† ϐ‹„”‘•‹•Ǥ Š‡•‡ ”‡•—Ž–• †‡‘•–”ƒ–‡† –Šƒ– ›”–‘Ž treatment down-”‡‰—Žƒ–‡†–Š‡…›–‘‹‡•ƒ†–Š‡Ž‡˜‡Ž•ȋ ‹‰Ǥ͹ǦȌ‹–Š‡”ƒ†‹ƒ–‹‘ induced lung injury mice Physiol Biochem 2016;38:619-634 Cellular Physiology Cell © 2016 The Author(s) Published by S Karger AG, Basel DOI: 10.1159/000438655 and Biochemistry Published online: February 08, 2016 www.karger.com/cpb 627 Zhao et al.: Myrtol Standardized on Radiation-Induced Lung Injury ’Ǧ’”‘–‡‹Ž‡˜‡Ž•ƒ–ʹƒ†ͳ͸™‡‡•’‘•–Ǧ‹””ƒ†‹ƒ–‹‘ȋ ‹‰ǤͺǢʹ™‡‡•Ǣͳ͸™‡‡•ȌǤ‡ƒŽǦ –‹‡ƒƒŽ›•‹•ƒŽ•‘‹†‹…ƒ–‡†–Šƒ–›”–‘Ž•‹‰‹ϐ‹…ƒ–Ž›ȋ’δͲǤͲͷǡ’δͲǤͲͳȌ‹Š‹„‹–‡†Ǧ ʹȀǦͻ‰‡‡‡š’”‡••‹‘‹Ž—‰–‹••—‡ƒ–†‹ˆˆ‡”‡––‹‡•ȋ ‹‰Ǥ͹ ƒ† ȌǤ Downloaded by: Univ of California San Diego 132.239.1.231 - 3/3/2017 8:59:18 AM Fig 6.š’”‡••‹‘‘ˆ•‡”—…›–‘‹‡•ƒ†Š›†”‘š›’”‘Ž‹‡‹Ž—‰–‹••—‡ˆ”‘†‹ˆˆ‡”‡–‰”‘—’•‹”ƒ†‹ƒ–‹‘ ‹†—…‡† ‹Œ—”› ‹…‡ ‘†‡Ž ƒ– ͳǡ ʹǡ Ͷǡ ͺǡ ͳ͸ ™‡‡• ’‘•– ‹””ƒ†‹ƒ–‹‘Ǥ ȋȌ Š‡ •‡”— Ž‡˜‡Ž• ‘ˆ –”ƒ•ˆ‘”‹‰ ‰”‘™–Šˆƒ…–‘”Ⱦͳȋ ǦȾͳȌȋȌ–—‘”‡…”‘•‹•ˆƒ…–‘”Ƚȋ ǦȽȌȋȌ‹–‡”Ž‡—‹ȋȌǦͳȾȋȌ‹–‡”Ž‡—‹ȋȌǦ͸ ƒ†ȋȌ ʹƒ†ȋ Ȍ›†”‘š›’”‘Ž‹‡ȋ›’Ȍ…‘–‡–Ǥƒ–ƒ™‡”‡’”‡•‡–‡†ƒ•‡ƒάȋα͸ǡȗ’δͲǤͲͷǡȗȗ ’δͲǤͲͳǡ˜•ǤΪ›”–‘ŽȌǤ Physiol Biochem 2016;38:619-634 Cellular Physiology Cell © 2016 The Author(s) Published by S Karger AG, Basel DOI: 10.1159/000438655 and Biochemistry Published online: February 08, 2016 www.karger.com/cpb 628 Fig 7.Š‡‡š’”‡••‹‘‘ˆ’”‘Ǧ‹ϐŽƒƒ–‘”›…›–‘‹‡•ƒ†–Š‡–‹••—‡‰”‘™–Šˆƒ…–‘”ǦȾͳȋ ǦȾͳȌ‹ ”ƒ†‹ƒ–‹‘‹†—…‡†‹Œ—”›‹…‡‘†‡Žƒ–ͳǡʹǡͶǡͺǡͳ͸™‡‡•’‘•–‹””ƒ†‹ƒ–‹‘ǤȋȌ ǦȾͳǡȋȌ ǦȽ ‡š’”‡••‹‘ǡȋȌǦͳȾ‡š’”‡••‹‘ǡȋȌǦ͸‡š’”‡••‹‘ǡȋȌ ‡š’”‡••‹‘ǡȋ Ȍ ʹ‡š’”‡••‹‘ǡȋ ȌͻǤƒ–ƒ™‡”‡’”‡•‡–‡†ƒ•‡ƒάƒ†‘„–ƒ‹‡†ƒ˜‡”ƒ‰‡˜ƒŽ—‡ ˆ‘”‡ƒ…Š™ƒ•—•‡†ˆ‘”•–ƒ–‹•–‹…•ǡα͸ǡȗԜδԜͲǤͲͷǡȗȗ’δͲǤͲͳǡ˜•ǤΪ›”–‘Ž‰”‘—’Ǥ Downloaded by: Univ of California San Diego 132.239.1.231 - 3/3/2017 8:59:18 AM Zhao et al.: Myrtol Standardized on Radiation-Induced Lung Injury Physiol Biochem 2016;38:619-634 Cellular Physiology Cell © 2016 The Author(s) Published by S Karger AG, Basel DOI: 10.1159/000438655 and Biochemistry Published online: February 08, 2016 www.karger.com/cpb 629 Zhao et al.: Myrtol Standardized on Radiation-Induced Lung Injury Fig 8. ›”–‘Ž ‹Š‹„‹–‡† –Š‡ ’Š‘•’Š‘”›Žƒ–‹‘ ‘ˆ  ƒ† †‘™Ǧ”‡‰—Žƒ–‡† –Š‡ ‡š’”‡••‹‘ Ž‡˜‡Ž ‘ˆ Ǧʹ ƒ†ǦͻǤ‡’”‡•‡–ƒ–‹˜‡‹ƒ‰‡•‘ˆ–Š‡’Š‘•’Š‘”›Žƒ–‹‘‘ˆƒ†‡š’”‡••‹‘Ž‡˜‡Ž‘ˆǦʹƒ†Ǧͻ‹ †‹ˆˆ‡”‡–‰”‘—’•ƒˆ–‡””ƒ†‹ƒ–‹‘ƒ–ʹȋȌƒ†ͳ͸™‡‡•ȋȌ™‡”‡†‡–‡…–‡†„›™‡•–‡”„Ž‘–Ǥ –Š‹••–—†›ǡ™‡’”‡•‡–‡†‡š’‡”‹‡–ƒŽ‡˜‹†‡…‡†‡‘•–”ƒ–‹‰–Š‡’”‘–‡…–‹˜‡‡ˆˆ‡…–• ‘ˆ›”–‘Ž‘”ƒ†‹ƒ–‹‘Ǧ‹†—…‡†Ž—‰‹Œ—”›Ǥ‡…‘ϐ‹”‡†–Šƒ–›”–‘Ž‘”ƒŽƒ†‹‹•–”ƒ–‹‘ ‘– ‘Ž› ƒ‡Ž‹‘”ƒ–‡† ‹…‡ ”ƒ†‹ƒ–‹‘ ’‡—‘‹–‹• ‹ ‡ƒ”Ž› ’Šƒ•‡ „—– ƒŽ•‘ ‹Š‹„‹–‡† Ž—‰ ϐ‹„”‘•‹•ˆ‘”ƒ–‹‘‹Žƒ––‡”’Šƒ•‡Ǥ›”–‘Ž–”‡ƒ–‡–…‘—Ž†”‡†—…‡Ž—‰…‘‡ˆϐ‹…‹‡–ǡ‹’”‘˜‡ Ž—‰ Š‹•–‘Ž‘‰‹…ƒŽ …Šƒ‰‡ǡ †‡…”‡ƒ•‡ ›’ …‘–‡–ǡ ”‡†—…‡ –Š‡ ”ƒ†‹ƒ–‹‘Ǧ‹†—…‡† ‘š‹†ƒ–‹˜‡ †ƒƒ‰‡‹‹…‡’—Ž‘ƒ”›ǡƒ†”‡‰—Žƒ–‡–Š‡Ž‡˜‡Ž•‘ˆ ǦȾͳǡ ǦȽǡǦͳȾǡǦ͸ƒ† ʹǤ ‡ ƒŽ•‘ •Š‘™‡† –Šƒ– ›”–‘Ž –”‡ƒ–‡– ‹Š‹„‹–‡†  ƒ…–‹˜ƒ–‹‘ ƒ† †‘™Ǧ”‡‰—Žƒ–‡† –Š‡ ƒ–”‹š ‡–ƒŽŽ‘’”‘–‡‹ƒ•‡ǦʹȋǦʹȌ ƒ† ƒ–”‹š ‡–ƒŽŽ‘’”‘–‡‹ƒ•‡ǦͻȋǦͻȌ ‡š’”‡••‹‘Ǥ …”‡ƒ•‹‰ ‡˜‹†‡…‡ ‹†‹…ƒ–• –Šƒ– ‘š‹†ƒ–‹˜‡ •–”‡•• ƒ†  …‘–”‹„—–‡ †‹”‡…–Ž› ƒ† ‹†‹”‡…–Ž›–‘–Š‡’”‘‰”‡••‹‘‘ˆ”ƒ†‹ƒ–‹‘Ǧ‹†—…‡†‹Œ—”›ȏʹͲȐǤŠ‡Ǧ‹†—…‡†ƒ…–‹˜ƒ–‹‘ ‘ˆ ‹ϐŽƒƒ–‘”› …‡ŽŽ• ‹…”‡ƒ•‡† ’”‘†—…–‹‘ ‘ˆ  ȏʹͳȐǤ ˜‡”„ƒŽƒ…‡ ‘ˆ ‘š‹†ƒ–‹˜‡ •–”‡•• ‹ –Š‡ Ž—‰ ‡’– ‹†—…‹‰ –‹••—‡ †ƒƒ‰‡ǡ –Š‡”‡ˆ‘”‡ǡ ƒ–‹‘š‹†ƒ– …‘’‘‡– ƒ› „‡ —•‡† ”‡‡†› ”ƒ†‹ƒ–‹‘Ǧ‹†—…‡† Ž—‰ ‹Œ—”›Ǥ Š‡”‡ ƒ”‡ ƒ Ž‘– ‘ˆ •–—†‹‡• •Š‘™‹‰ –Šƒ– –Š‡ ›”–‘Ž Šƒ˜‡‡ˆˆ‡…–‹˜‡ƒ–‹‘š‹†ƒ–ƒ…–‹˜‹–›ǡ™Š‹…Š…ƒ„‡—•‡†ƒ••…ƒ˜‡‰‡”‘ˆƒ†ˆ”‡‡”ƒ†‹…ƒŽ• ȏʹʹǦʹ͸ȐǤ–…ƒ„‡•Š‘™–Šƒ–›”–‘Ž–ƒ†ƒ”†‹œ‡†ƒ‡Ž‹‘”ƒ–‡•‹ϐŽƒƒ–‘”›’”‘…‡••‡•„› ‹–‡”ƒ…–‹‰™‹–Šƒ‰‰”‡••‹˜‡‘š›‰‡”ƒ†‹…ƒŽ•‘ˆ–Š‡ȉƒ†‹–‡”ˆ‡”‡™‹–ŠŽ‡—‘…›–‡ƒ…–‹˜ƒ–‹‘ ȏͳͲȐǤ  Ž‡˜‡Ž• ”‡ϐŽ‡…– ‹…‡ Ž‹’‹† ’‡”‘š‹†ƒ–‹‘ †ƒƒ‰‡ ƒ† …ƒ ‹†‹…ƒ–‡ †ƒƒ‰‡ –‘ …‡ŽŽ ‡„”ƒ‡•ȏʹ͹ȐǤ–Š‡‘–Š‡”Šƒ†’Žƒ›•ƒ…”—…‹ƒŽ”‘Ž‡‹ƒ–‹‘š‹†ƒ–‹‘Ǥˆ–‡”–Š‡†‹•…‘˜‡”› ‘ˆ‹ͳͻ͸ͻȏʹͺǡʹͻȐǡ‹–™ƒ•ˆ‘—†–‘’”‘–‡…–•‹’Ž‡„‹‘Ž‘‰‹…•›•–‡•ˆ”‘•—’‡”‘š‹†‡ ”ƒ†‹…ƒŽ–‘š‹…‹–›Ǥ‹…‡–Š‡ǡŠƒ•„‡‡ˆ‘—†–‘†‡…”‡ƒ•‡”ƒ†‹ƒ–‹‘†ƒƒ‰‡‹ƒ™‹†‡”ƒ‰‡ ‘ˆ„‹‘Ž‘‰‹…•›•–‡•ǤŠ‡”‡ƒ”‡•‘‡•–—†‹‡•†‡•…”‹„‹‰–Š‡ƒ–‹‘š‹†ƒ–ƒ…–‹˜‹–‹‡•‘ˆ†‹ˆˆ‡”‡– ‡š–”ƒ…–‘ˆ›”–Ž‡ȏ͵Ͳǡ͵ͳȐǤ›”–‘ŽŠƒ•„‡‡’”‘˜‡†–‘‡š‡”–ƒ–‹Ǧ‘š‹†ƒ–‹˜‡ƒ†ƒ–‹„ƒ…–‡”‹ƒŽ activities via oligomeric, non-prenylated acylphloroglucinols such as myrtucommulone and •‡‹Ǧ›”–—…‘—Ž‘‡ȏ͵ʹǡ͵͵ȐǤƒ‘–Š‡”•–—†›ǡ„Žƒ…Myrtus communis „‡””‹‡•…‘–‡– Š‹‰ŠŽ‡˜‡Ž‘ˆƒ–Š‘…›ƒ‹•ƒ†ϐŽƒ˜‘‘‹†••Š‘™Š‹‰Š”ƒ†‹…ƒŽ•…ƒ˜‡‰‹‰ƒ…–‹˜‹–‹‡•ȏ͵ͶȐǤ ‘—”’”‡•‡–•–—†›ǡ™‡ƒŽ•‘ˆ‘—†–Šƒ––Š‡Ž‡˜‡Ž•‘ˆŽ—‰–‹••—‡•‹‰‹ϐ‹…ƒ–Ž›†‡…”‡ƒ•‡†ȋ’ δͲǤͲͷǡ’δͲǤͲͳȌ™Š‹Ž‡ƒ…–‹˜‹–›‹…”‡ƒ•‡†ƒŽ‘‰™‹–Š–Š‡–”‡ƒ–‡–‘ˆ›”–‘Žȋ’δͲǤͲͷǡ ’δͲǤͲͳȌȋ ‹‰ǤͷȌǤ‡ƒŽ•‘ˆ‘—†–Šƒ–ƒ–‹‘š‹†ƒ–ƒ…–‹˜‹–›‘ˆ›”–‘Ž™ƒ•’”‡•‡”˜‡†‹‘”‡ –Šƒ͵‘–Š•ƒ•†‡•…”‹„‡†„›‘–‘”‘‡–ƒŽǤ ȏ͵ͷȐǤ––Š‡•ƒ‡–‹‡‘—””‡•—Ž–••Š‘™‡†–Šƒ– Downloaded by: Univ of California San Diego 132.239.1.231 - 3/3/2017 8:59:18 AM Discussion Physiol Biochem 2016;38:619-634 Cellular Physiology Cell © 2016 The Author(s) Published by S Karger AG, Basel DOI: 10.1159/000438655 and Biochemistry Published online: February 08, 2016 www.karger.com/cpb 630 ’”‡†‹•‘‡ ‰”‘—’ ”‡†—…‡†  Ž‡˜‡Ž ‘Ž› ‹ ϐ‹”•– Ͷ ™‡‡• ƒˆ–‡” ”ƒ†‹ƒ–‹‘Ǥ Š‡•‡ ”‡•—Ž–• •—‰‰‡•– –Šƒ– ›”–‘Ž …ƒ ”‡†—…‡ ‘š‹†ƒ–‹˜‡ †ƒƒ‰‡ǡ ƒ† ‹…”‡ƒ•‡ ƒ–‹‘š‹†ƒ– ’”‘–‡‹• ƒ† alleviates radiation lung injuries – ͶǦͺ ™‡‡• ƒˆ–‡” ‹””ƒ†‹ƒ–‹‘ǡ –Š‡ Ž—‰ –‹••—‡ Šƒ† ‹…”‡ƒ•‡† †‡’‘•‹–‹‘ Ž‡˜‡Ž• ‘ˆ Š›†”‘š›’”‘Ž‹‡ …‘–‡– ȋ ‹‰Ǥ ͸ Ȍǡ ™Š‹…Š ™ƒ• ”‡‰ƒ”†‡† ƒ• ƒ ƒ”‡” ‘ˆ –Š‡ Ž‡˜‡Ž ‘ˆ …‘ŽŽƒ‰‡…‘–‡–ȏ͵͸ȐǤ›†”‘š›’”‘Ž‹‡‹Ž—‰–‹••—‡™‡”‡†‡–‡…–‡†„›—•‹‰ƒŠ›†”‘š›’”‘Ž‹‡ ƒ••ƒ›‹–Ǥ‡ˆ‘—†–Šƒ–›”–‘Ž†”ƒƒ–‹…ƒŽŽ›†‡…”‡ƒ•‡†–Š‡›’…‘–‡–ƒ†ƒŽŽ‡˜‹ƒ–‡†–Š‡ Ž—‰–‹••—‡ϐ‹„”‘•‹•ˆ‘”ƒ–‹‘‹Ͷǡͺǡͳ͸™‡‡•ǡ‡˜‡–Š‘—‰Š–Š‡–”‡ƒ–‡–‘ˆ’”‡†‹•‘‡ …‘—Ž†”‡†—…‡‡ƒ”Ž›”ƒ†‹ƒ–‹‘Ǧ‹†—…‡†’‡—‘‹–‹•Ǥ‘™‡˜‡”ǡ‹–†‹†‘–•Š‘™‹Š‹„‹–‹‘‘ˆ–Š‡ Žƒ––‡”ϐ‹„”‘•‹•ˆ‘”ƒ–‹‘Ǥ‘˜‡”•‡Ž›ǡŽ‘‰–‡”ƒ†‹‹•–”ƒ–‹‘‘ˆ’”‡†‹•‘‡•Š‘™‡†•‘‡ •‡˜‡”‡•‹†‡‡ˆˆ‡…–•‹…Ž—†‹‰™‡‹‰Š–Ž‘••ǡ‘•–‡‘’‘”‘•‹•ǡ‹ˆ‡…–‹‘ƒ†…ƒ”†‹‘Ǧ…‡”‡„”‘˜ƒ•…—Žƒ” complications ‘‹˜‡•–‹‰ƒ–‡–Š‡‡…Šƒ‹•‘ˆ›”–‘Ž–”‡ƒ–‡–‘‹ϐŽƒƒ–‹‘ǡ™‡‡ƒ•—”‡†–Š‡ •‡”—Ž‡˜‡Ž•‘ˆ‡›‹ϐŽƒƒ–‘”›…›–‘‹‡•‹…Ž—†‹‰ ǦȾͳǡ ǦȽǡǦͳȾǡǦ͸ƒ† ʹ ȋ ‹‰Ǥ ͸ȌǤ Š‡  ”‡•—Ž–• •Š‘™‡† –Šƒ– ›”–‘Ž ƒ––‡—ƒ–‡† ‹…‡ ‹ϐŽƒƒ–‹‘ …›–‘‹‡•Ǥ Š‡•‡…›–‘‹‡•™‡”‡•‹‰‹ϐ‹…ƒ–Ž›”‡†—…‡†ȋ’δͲǤͲͷǡ’δͲǤͲͳȌ‹–Š‡›”–‘ŽǦ–”‡ƒ–‡†ƒ‹ƒŽ• compared with the untreated radiated treated mice, and these effects lasted for months after treatment ceased  ǦȾͳ Šƒ• „‡‡ •Š‘™ ’Žƒ›‹‰ ƒ …”‹–‹…ƒŽ ”‘Ž‡ ‹ –Š‡ †‡˜‡Ž‘’‡– ‘ˆ ’—Ž‘ƒ”› ϐ‹„”‘•‹• ƒ† ‡’‹–Š‡Ž‹ƒŽ ‡•‡…Š›ƒŽ –”ƒ•‹–‹‘ ȋȌ ȏ͵͹ǦͶͲȐǤ  ǦȾͳ ™ƒ• •Š‘™ –‘ ’”‘‘–‡ϐ‹„”‘„Žƒ•–’”‘Ž‹ˆ‡”ƒ–‹‘ƒ†ƒ–—”ƒ–‹‘ǡ–Š‡”‡„›ƒ……‡Ž‡”ƒ–‹‰–Š‡†‡˜‡Ž‘’‡–‘ˆ ’—Ž‘ƒ”›ϐ‹„”‘•‹•ȏͶͳȐǤŽ‘…‹‰ ǦȾͳ‘”‹–•ƒ…–‹˜ƒ–‹‘…‘—Ž†–Š—•„‡‡ˆˆ‡…–‹˜‡–”‡ƒ–‡–• ˆ‘””ƒ†‹ƒ–‹‘‹†—…‡Ž—‰‹Œ—”›Ǥ—„‡”‘ˆ‹ϐŽƒƒ–‘”›…›–‘‹‡•‹…Ž—†‹‰ ǦȽƒ† ǦͳȾƒ”‡‘˜‡”‡š’”‡••‡†‹Ž—‰–‹••—‡ˆ”‘”ƒ†‹ƒ–‹‘‹†—…‡Ž—‰‹Œ—”›‹…‡‘†‡Žǡ™Š‹…Š ‹•‘™–‘•—•–ƒ‹ ǦȾͳ‡š’”‡••‹‘ƒ†–‘’”‘‘–‡–Š‡’”‘‰”‡••‹‘‘ˆ–Š‡’—Ž‘ƒ”› ϐ‹„”‘•‹•Ǥ ‘”‡‘˜‡”ǡ ‘—” in vivo ”‡•—Ž–• •Š‘™‡† –Šƒ– ›”–‘Ž †‡…”‡ƒ•‡† –Š‡ ‡š’”‡••‹‘ ‘ˆ ˜‹‡–‹ ƒ† ȽǦ ƒ† ‹…”‡ƒ•‡† –Š‡ Ž‡˜‡Ž• ‘ˆ Ǧ…ƒ†Š‡”‹ ȋ ‹‰Ǥ ͶȌǤ Š‡•‡ ‹†‹…ƒ–‡ –Šƒ– ›”–‘Ž …‘—Ž† ‹Š‹„‹–  ǦȾͳ ‡†‹ƒ–‡† –”ƒ•†‹ˆˆ‡”‡–‹ƒ–‹‘ǡ ’‘–‡–‹ƒŽŽ› ˜‹ƒ ‹–• ƒ–‹‘š‹†ƒ– ƒ†ƒ–‹Ǧ‹ϐŽƒƒ–‘”›ƒ…–‹˜‹–‹‡•Ǥ  ǦȽ‹•ƒ’Ž‡‹‘–”‘’‹……›–‘‹‡‹”‡•’‘•‡–‘‹ˆ‡…–‹‘‘”‹Œ—”›ȏͶʹȐǤ ǦȽ‡†‹ƒ–‡• Ž—‰ …›–‘‹‡ ‡–™‘”‹‰ ƒ† ‡‘•‹‘’Š‹Ž ”‡…”—‹–‡– ‹ ’—Ž‘ƒ”› ϐ‹„”‘•‹•Ǥ  ǦȽ ’Žƒ›• ƒ ˜‹–ƒŽ ”‘Ž‡ ‹ ’”‘Ǧ‹ϐŽƒƒ–‘”› ‡–™‘”• ƒ† ƒ› „‡ ‹˜‘Ž˜‡† ‹ –Š‡ †‡˜‡Ž‘’‡– ƒ† ’”‘‰”‡••‹‘‘ˆ”ƒ†‹ƒ–‹‘Ǧ‹†—…‡†’‡—‘‹–‹•–Š”‘—‰Š‹†—…‹‰ ǦȾͳ‡š’”‡••‹‘‹Ž—‰ ϐ‹„”‘„Žƒ•–•ȏͶ͵ǡͶͶȐ. —”–Š‡”‘”‡ǡ ǦȽ’‘Ž›‘”’Š‹••‹†‹…ƒ–‹˜‡‘ˆŠ‹‰ŠŽ‡˜‡Ž•‘ˆ ǦȽ ‡š’”‡••‹‘…‘””‡Žƒ–‡™‹–Šƒ‹…”‡ƒ•‡†”‹•‘ˆ†‡˜‡Ž‘’‹‰‹–‡”•–‹–‹ƒŽ’—Ž‘ƒ”›ϐ‹„”‘•‹•ȋ Ȍ ȏͶͷ,Ͷ͸ȐǤ ǦȽƒ…–‹˜ƒ–‡•ϐ‹„”‘„Žƒ•–•’”‘Ž‹ˆ‡”ƒ–‹‘ƒ†•–‹—Žƒ–‡•‡…”‡–‹‘’”‘Ǧ‹ϐŽƒƒ–‘”› …›–‘‹‡•ǡ ‹…Ž—†‹‰ Ǧͳ ƒ† Ǧ͸ ‹ ‡—–”‘’Š‹Ž• ƒ† ƒ…”‘’Šƒ‰‡• ȏͶ͹ȐǤ Ǧ͸ ƒŽ•‘ ’Žƒ›• ƒ ‹’‘”–ƒ– ”‘Ž‡ ‹ –Š‡ …‘‡…–‹˜‡ –‹••—‡ ϐ‹„‡”‹œƒ–‹‘ǡ ’‘–‡–‹ƒŽŽ› „› ‹…”‡ƒ•‹‰ …‘ŽŽƒ‰‡ †‡’‘•‹–‹‘ǡ ‹Š‹„‹–‹‰ ‡š–”ƒ…‡ŽŽ—Žƒ” ƒ–”‹š ȋȌ †‡‰”ƒ†ƒ–‹‘ǡ ƒ† •–‹—Žƒ–‹‰ ϐ‹„”‘„Žƒ•– ’”‘Ž‹ˆ‡”ƒ–‹‘Ǥ”‡˜‹‘—••–—†‹‡•Šƒ˜‡•—‰‰‡•–‡†–Šƒ–Ǧ͸Ž‡ƒ†•–‘‹ϐŽƒƒ–‹‘ƒ†ϐ‹„”‘•‹• ƒ••‘…‹ƒ–‡†™‹–ŠŠ›’‡”•‡•‹–‹˜‹–›’‡—‘‹–‹•‹‹…‡ȏͶͺ,ͶͻȐǤŠ‡•‡”‡•—Ž–••—‰‰‡•–ƒ…Ž‘•‡ ”‡Žƒ–‹‘•Š‹’‹Ǧ͸ƒ†’‡—‘‹–‹•ƒ†ϐ‹„”‘–‹…†‡˜‡Ž‘’‡–Ǥ—””‡•—Ž–••Š‘™‡† –Šƒ–Ǧ͸Ž‡˜‡Ž•™‡”‡”‡†—…‡†„››”–‘Ž‹‡ƒ”Ž›Ͷ™‡‡•Ǥ›”–‘ŽƒŽ•‘‡ˆˆ‡…–‹˜Ž›”‡†—…‡†Ǧ ͳȾǡ™Š‹…Š‹•‘‡‘ˆ’”‘Ǧ‹ϐŽƒƒ–‘”›…›–‘‹‡•–Š‘—‰Š––‘„‡‹˜‘Ž˜‡†‹ƒ›ƒ…—–‡ƒ† chronic diseases ”‘•–ƒ‰Žƒ†‹ʹȋ ʹȌ‹•…‘‘Ž›”‡‰ƒ”†‡†ƒ•ƒ’‘–‡–’”‘Ǧ‹ϐŽƒƒ–‘”›‡†‹ƒ–‘” ƒ† ‹• ‹˜‘Ž˜‡† ‹ •‡˜‡”ƒŽ ‹ϐŽƒƒ–‘”› †‹•‡ƒ•‡• ȏͷͲȐǤ  ʹ …ƒ ”‡‰—Žƒ–‡ Ž›’Š‘…›–‡ –”ƒˆϐ‹…‹‰ ‹–‘ –‹••—‡ ƒ† ‹– …ƒ ƒŽ•‘ ‹Š‹„‹– Šʹ †‹ˆˆ‡”‡–‹ƒ–‹‘Ǥ  ‘—” •–—†›ǡ ’—Ž‘ƒ”› ‹””ƒ†‹ƒ–‹‘•–‹—Žƒ–‡†–Š‡’”‘†—…–‹‘‘ˆ•‡˜‡”ƒŽ…›–‘‹‡•‹–Š‡‡ƒ”Ž›•–ƒ‰‡ƒ†…‘•‡“—‡–Ž› •–‹—Žƒ–‡†–Š‡”‡Ž‡ƒ•‡‘ˆ‰”‡ƒ–ƒ‘—–•‘ˆ ʹ„›ϐ‹„”‘„Žƒ•–Ǥ‡ˆ‘—†–Šƒ–›”–‘Ž…‘—Ž† •‹‰‹ϐ‹…ƒ–Ž›”‡†—…‡ȋ’δͲǤͲͷǡ’δͲǤͲͳȌ ʹ‡š’”‡••‹‘‹‡ƒ”Ž›•–ƒ‰‡Ǥ‘™‡˜‡”ǡ ʹƒŽ•‘ ’Žƒ›•ƒ‡‰ƒ–‹˜‡ˆ‡‡†„ƒ…”‘Ž‡‹…›–‘‹‡’”‘†—…–‹‘ƒ††‘™Ǧ”‡‰—Žƒ–‡ϐ‹„”‘„Žƒ•–‡–ƒ„‘Ž‹… ˆ—…–‹‘•‹…Ž—†‹‰’”‘Ž‹ˆ‡”ƒ–‹‘ǡ…‘ŽŽƒ‰‡•›–Š‡•‹•ƒ†–”ƒ•‹–‹‘–‘›‘ϐ‹„”‘„Žƒ•–•ȏͷͳȐǤ –Š‡Žƒ–‡”’Šƒ•‡ȋͺǦͳ͸™‡‡•’‘•–”ƒ†‹ƒ–‹‘Ȍǡ–Š‡”‡™ƒ•ƒ†‘™”‡‰—Žƒ–‹‘‘ˆ–Š‡‡š’”‡••‹‘ Downloaded by: Univ of California San Diego 132.239.1.231 - 3/3/2017 8:59:18 AM Zhao et al.: Myrtol Standardized on Radiation-Induced Lung Injury Physiol Biochem 2016;38:619-634 Cellular Physiology Cell © 2016 The Author(s) Published by S Karger AG, Basel DOI: 10.1159/000438655 and Biochemistry Published online: February 08, 2016 www.karger.com/cpb 631 Zhao et al.: Myrtol Standardized on Radiation-Induced Lung Injury ‘ˆ ʹǡƒ•’”‡˜‹‘—•Ž›”‡’‘”–‡†‹ϐ‹„”‘–‹…ϐ‹„”‘„Žƒ•–•ƒ††ƒƒ‰‡†Ž—‰‡’‹–Š‡Ž‹ƒŽ…‡ŽŽ•ȏͷʹȐǡ –Š—•’‘–‡–‹ƒŽŽ›Ž‡ƒ†‹‰–‘–Š‡’‡”•‹•–‡…‡‘ˆ‹—‡ƒ…–‹˜ƒ–‹‘ƒ†…Š”‘‹…‹ϐŽƒƒ–‹‘Ǥ ‘—”•–—†›ǡ›”–‘Ž‰”‘—’’”‡•‡”˜‡†Š‹‰ŠŽ‡˜‡Ž‘ˆ ʹ‹Žƒ––‡”ϐ‹„”‘•‹••–ƒ‰‡…‘’ƒ”‡† ™‹–Š‹””ƒ†‹ƒ–‹‘‘Ž›‰”‘—’ƒ†’”‡†‹•‘‡‰”‘—’ǡ‹†‹…ƒ–‹‰ƒ”‘Ž‡‘ˆ›”–‘Žƒ† ʹ‘ Ž—‰–‹••—‡†ƒƒ‰‡•‹Žƒ–‡–•–ƒ‰‡ǡ‹…Ž—†‹‰Ž‹‹–‹‰–Š‡‹—‡Ǧ‹ϐŽƒƒ–‘”›”‡•’‘•‡ as well as tissue repair process ƒ–”‹š ‡–ƒŽŽ‘’”‘–‡‹ƒ•‡• ȋ•Ȍ ’Žƒ› ƒ ‡••‡–‹ƒŽ ”‘Ž‡ ‹ Ž—‰ ‹Œ—”› ƒ••‘…‹ƒ–‡† with tissue remodeling structural proteins such as collagens and elastin structural proteins •—…Š ƒ• …‘ŽŽƒ‰‡• ƒ† ‡Žƒ•–‹ ȏͷ͵ȐǤ ‘”‡‘˜‡”ǡ •–”‘‰ ‡˜‹†‡…‡• •Š‘™ –Šƒ–  •‹‰ƒŽ‹‰ ’ƒ–Š™ƒ› ’Žƒ›• ƒ …”‹–‹…ƒŽ ”‘Ž‡ ‹ ’”‘‘–‹‰ Ǧʹ ƒ† Ǧͻ ‡š’”‡••‹‘ ȏͷͶȐǤ ƒ–”‹š ‡–ƒŽŽ‘’”‘–‡‹ƒ•‡• ȋ•Ȍǡ ƒ ˆƒ‹Ž› ‘ˆ Ǧ†‡’‡†‡– ‡†‘’‡’–‹†ƒ•‡•ǡ †‡‰”ƒ†‡ ƒŽŽ ‹†• ‘ˆ ‡š–”ƒ…‡ŽŽ—Žƒ” ƒ–”‹š ȋȌ ’”‘–‡‹•ǡ ƒ† ’ƒ”–‹…‹’ƒ–‡ ‹ –—‘” ’”‘‰”‡••‹‘ ‹…Ž—†‹‰ ‰”‘™–Šǡƒ‰‹‘‰‡‡•‹•ǡ–‹••—‡‹˜ƒ•‹‘ƒ†‹‰”ƒ–‹‘ȏͷͷȐǤ‡Žƒ‡–ƒŽǤ ȏͷ͸Ȑˆ‘—†–Šƒ–  ’ƒ–‹‡–Ǧʹƒ†ǦͻŠ‹‰Š‡š’”‡••‹‘…‘–”‹„—–‡•–‘Ž—‰ϐ‹„”‘•‹•Ǥ‘”„‡Ž‡–ƒŽ.ȏͷ͹Ȑ —•‡†•‹Š‹„‹–‘”„ƒ–‹ƒ•–ƒ–…ƒ•‹‰‹ϐ‹…ƒ–Ž›”‡†—…‡‹…‡’—Ž‘ƒ”›ϐ‹„”‘•‹•Ǥ—‰ƒ‡– al.ȏͷͺȐ”‡’‘”–‡†–Šƒ–Ǧʹ‹‰Š–…‘–”‹„—–‡–‘’—Ž‘ƒ”›•–”—…–—”ƒŽ”‡‘†‡Ž‹‰–Š”‘—‰Š –›’‡…‘ŽŽƒ‰‡‘Ž›–‹…ƒ…–‹˜‹–›Ǥ–Š‹••–—†›ǡ™‡•Š‘™–Šƒ–›”–‘Ž”‡ƒ”ƒ„Ž›†‘™”‡‰—Žƒ–‡• •‡…”‡–‹‘‘ˆ„‘–ŠǦʹƒ†ǦͻǤŠ‹Ž‡’”‡†‹•‘‡Šƒ˜‹‰‘‰”‡ƒ–‡ˆˆ‡…–‘ǦʹȀǦͻ •‡…”‡–‹‘…‘’ƒ”‡†™‹–Š”ƒ†‹ƒ–‹‘‘Ž›‰”‘—’Ǥ—”™‡•–‡”„Ž‘–ƒƒŽ›•‹•”‡•—Ž–•”‡˜‡ƒŽ‡† –Šƒ–›”–‘Ž‡Šƒ…‡†–Š‡‡š’”‡••‹‘Ž‡˜‡Ž•‘ˆǦ…ƒ†Š‡”‹ǡƒ†”‡†—…‡†ǡ’ǦǡǦ ʹȀǦͻ‡š’”‡••‹‘‹‹…‡Ž—‰–‹••—‡•…‘’ƒ”‡†™‹–Š”ƒ†‹ƒ–‹‘Ǧ‘Ž›‹…‡ǤŠ‡™‡•–‡”„Ž‘– ”‡•—Ž–•Š‘™‡†–Šƒ––Š‡‡š’”‡••‹‘•ƒ†ƒ…–‹˜‹–‹‡•‘ˆǦʹƒ†Ǧͻ™‡”‡‹Š‹„‹–‡†„› ›”–‘Žƒ†‹‹•–”ƒ–‹‘ǡƒ†‹Š‹„‹–‡†‘ˆ’ƒ–Š™ƒ›™Š‹…Š’Žƒ›‡†‹’‘”–ƒ–”‘Ž‡•‹Ǥ Conclusion …‘…Ž—•‹‘ǡ–Š‡’”‡•‡–”‡•—Ž–•Šƒ˜‡•Š‘™–Šƒ–›”–‘Ž–”‡ƒ–‡–’”‘˜‹†‡•’‡”•‹•–‡– ƒ–‹‘š‹†ƒ–ǡ ƒ–‹Ǧ‹ϐŽƒƒ–‘”›ǡ ƒ† ƒ–‹Ǧϐ‹„”‘•‹• ‡ˆˆ‡…–• –Šƒ– ’”‘–‡…– ƒ‰ƒ‹•– ”ƒ†‹ƒ–‹‘Ǧ ‹†—…‡† ‹Œ—”›Ǥ Š‡•‡ ϐ‹†‹‰• •—‰‰‡•– –Šƒ– ›”–‘Ž ‹‰Š– •—’’”‡••  ’”‘…‡•• –Š”‘—‰Š ‹Š‹„‹–‹‰ ‘ˆ  ƒ…–‹˜ƒ–‹‘Ǥ Š‡•‡ ϐ‹†‹‰• •—‰‰‡•– –Šƒ– ›”–‘Ž Šƒ• ‰”‡ƒ– ’‘–‡–‹ƒŽ –‘ „‡ used in treating radiotherapy complications in terms of protecting from radiation-induced lung injury Acknowledgments Š‡ ƒ—–Š‘”• ™‹•Š –‘ –Šƒ ‡› ƒ˜› š’‡”‹‡– ‡–‡” ‘ˆ ‡…‘† ‹Ž‹–ƒ”› ‡†‹…ƒŽ ‹˜‡”•‹–›ǯ• •–ƒˆˆ ˆ‘” ‘ˆˆ‡”‹‰ –Š‡‹” –‡…Š‹…ƒŽ ƒ† ƒ†‹‹•–”ƒ–‹˜‡ •—’’‘”–Ǥ Š‹• ™‘” ™ƒ• •—’’‘”–‡† „› ‰”ƒ–• ˆ”‘ –Š‡ ƒ–‹‘ƒŽ ƒ–—”ƒŽ …‹‡…‡ ‘—†ƒ–‹‘ ‘ˆ Š‹ƒ ȋ ”ƒ–• ‘Ǥ ͺͳͶ͹ʹͻͳͳȌƒ†ƒ–—”ƒŽ…‹‡…‡ ‘—†ƒ–‹‘‘ˆŠƒ‰Šƒ‹ȋ‘ǤͳͶͳͶͶͻʹͲͲȌǤ Disclosure Statement The authors declare that they have no interests of any kind that could inappropriately ‹ϐŽ—‡…‡ȋ„‹ƒ•Ȍ–Š‡’—„Ž‹…ƒ–‹‘‘ˆ–Š‹•’ƒ’‡”Ǥ ƒ”•ǡ—ǡ—Œƒ•‘˜‹…ǡƒŽŽ ”ǡ ‘Žœǡ•…Š‡”ǣƒ†‹ƒ–‹‘Ǧ‹†—…‡†Ž—‰‹Œ—”›Ǥ‡‹ƒ†‹ƒ– …‘ŽʹͲͲ͵Ǣͳ͵ǣ͵͵͵Ǧ͵ͶͷǤ Downloaded by: Univ of California San Diego 132.239.1.231 - 3/3/2017 8:59:18 AM References Physiol Biochem 2016;38:619-634 Cellular Physiology Cell © 2016 The Author(s) Published by S Karger AG, Basel DOI: 10.1159/000438655 and Biochemistry Published online: February 08, 2016 www.karger.com/cpb 632 Zhao et al.: Myrtol Standardized on Radiation-Induced Lung Injury 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 ’’‡”Ž›ǡ‘‰Ž‹ƒ‰ ǡ ”‡––‘ ǡ ”‡‡„‡”‰‡” ǣ‘‡ƒ””‘™‘”‹‰‹‘ˆ›‘ϐ‹„”‘„Žƒ•–•‹‹””ƒ†‹ƒ–‹‘ ’—Ž‘ƒ”›ϐ‹„”‘•‹•Ǥ ‡•’‹”‡ŽŽ‘Ž‹‘ŽʹͲͲ͵Ǣʹͻǣʹͳ͵ǦʹʹͶǤ ‘—‡ǡ—‹–‘Šǡ‡‹‡ǡ—‹ǡ‘——›‡ǡƒ‹Œ‘ǣƒ†‹ƒ–‹‘’‡—‘‹–‹•‹Ž—‰…ƒ…‡”’ƒ–‹‡–•ǣƒ ”‡–”‘•’‡…–‹˜‡•–—†›‘ˆ”‹•ˆƒ…–‘”•ƒ†–Š‡Ž‘‰Ǧ–‡”’”‘‰‘•‹•Ǥ– ƒ†‹ƒ–…‘Ž‹‘ŽŠ›•ʹͲͲͳǢͶͻǣ͸ͶͻȂ ͸ͷͷǤ ‡Žƒ‹ƒǡ‡ˆƒ‹š ǣ—””‡–ƒƒ‰‡‡–ˆ‘”Žƒ–‡‘”ƒŽ–‹••—‡‹Œ—”›ǣ”ƒ†‹ƒ–‹‘Ǧ‹†—…‡†ϐ‹„”‘•‹•ƒ† ‡…”‘•‹•Ǥ‡‹ƒ†‹ƒ–…‘ŽʹͲͲ͹Ǣͳ͹ǣͻͻȂͳͲ͹Ǥ ‡‘”‰‡ǡ‹…Šƒ‡Žǡƒ˜‹†ǡ†™ƒ”†ǡ ƒ‡ǣ”‡†‹…–‹‘‘ˆ”ƒ†‹ƒ–‹‘’‡—‘‹–‹•„›†‘•‡Ȃ˜‘Ž—‡ Š‹•–‘‰”ƒ’ƒ”ƒ‡–‡”•‹Ž—‰…ƒ…‡”Ȅƒ•›•–‡ƒ–‹…”‡˜‹‡™Ǥƒ†‹‘–Š‡”…‘ŽʹͲͲͶǢ͹ͳǣͳʹ͹Ǧͳ͵ͺǤ —„‹ǡ ‘Š•–‘ǡ‹ŽŽ‹ƒ• ǡ…‘ƒŽ†ǡ ‹‡Ž•–‡‹ ǣ‡”’‡–—ƒŽ…ƒ•…ƒ†‡‘ˆ…›–‘‹‡•’‘•–Ǧ‹””ƒ†‹ƒ–‹‘ Ž‡ƒ†•–‘’—Ž‘ƒ”›ϐ‹„”‘•‹•Ǥ– ƒ†‹ƒ–…‘Ž‹‘ŽŠ›•ͳͻͻͷǢ͵͵ǣͻͻǦͳͲͻǤ ò„‡ǡ‹Žˆ‡”– ǡƒŽ ǡڐ‹‰ ǡ—”†ƒǦ‘–Šƒǡ‹—ǡ…Š—…ǡ‹ŽŽ‹…Šǡò„‡ǣ””ƒ†‹ƒ–‹‘ ‹†—…‡•ƒ„‹’Šƒ•‹…‡š’”‡••‹‘‘ˆ’”‘Ǧ‹ϐŽƒƒ–‘”›…›–‘‹‡•‹–Š‡Ž—‰Ǥ–”ƒŠŽ‡–Š‡”‘Ž ʹͲͲͶǢͳͺͲǣͶͶʹǦͶͶͺȋͶͶ͹ȌǤ ƒ––Š›•ǡ‡›ǡ‡ǡƒ”Ž•ǡ›ǡ ‡‹„ǡ‹––‹‰ǣˆϐ‹…ƒ…›ƒ†–‘Ž‡”ƒ„‹Ž‹–›‘ˆ›”–‘Ž•–ƒ†ƒ”†‹œ‡†‹ ƒ…—–‡„”‘…Š‹–‹•ǣƒ—Ž–‹Ǧ…‡–”‡ǡ”ƒ†‘‹•‡†ǡ†‘—„Ž‡Ǧ„Ž‹†ǡ’Žƒ…‡„‘Ǧ…‘–”‘ŽŽ‡†’ƒ”ƒŽŽ‡Ž‰”‘—’…Ž‹‹…ƒŽ–”‹ƒŽ ˜•Ǥ‡ˆ—”‘š‹‡ƒ†ƒ„”‘š‘ŽǤ”œ‡‹‹––‡Žˆ‘”•…Š—‰ʹͲͲͲǢͷͲǣ͹ͲͲǦ͹ͳͳǤ ƒ–œ•…Šǡƒ……ƒ ǡò…ǡ ‹ŽŽ‹••‡ǣ–‹Ǧ‹ϐŽƒƒ–‘”›‡ˆˆ‡…–•‘ˆ›”–‘Ž•–ƒ†ƒ”†‹œ‡†ƒ†‘–Š‡” ‡••‡–‹ƒŽ‘‹Ž•‘ƒŽ˜‡‘Žƒ”ƒ…”‘’Šƒ‰‡•ˆ”‘’ƒ–‹‡–•™‹–Š…Š”‘‹…‘„•–”—…–‹˜‡’—Ž‘ƒ”›†‹•‡ƒ•‡Ǥ—”  ‡†‡•‡ʹͲͲͻǢͳͶǣͳǦͷǤ ”ƒ••ƒ ǡ‹’’‡Ž‹ǡ‘”‹•…Šǡ‘Š‡”–ǡ‡—•…Š‡”ǡŽ•–‡” ǣ–‹‘š‹†ƒ–’”‘’‡”–‹‡•‘ˆ‡••‡–‹ƒŽ ‘‹Ž•Ǥ‘••‹„Ž‡‡š’Žƒƒ–‹‘•ˆ‘”–Š‡‹”ƒ–‹Ǧ‹ϐŽƒƒ–‘”›‡ˆˆ‡…–•Ǥ”œ‡‹‹––‡Žˆ‘”•…Š—‰ʹͲͲͲǢͷͲǣͳ͵ͷǦͳ͵ͻǤ ‹ Ǥ‘•‹–‹˜‡’”‡••—”‡–‡…Š‹“—‡•ˆ‘”ƒ‹”™ƒ›…Ž‡ƒ”ƒ…‡Ǥ‡•’‹”ƒ”‡ʹͲͲʹǢͶ͹ǣ͹ͺ͸Ǧ͹ͻ͸Ǥ ƒ ǡ‹ŽŒ‘‡ǣ–‹‹…”‘„‹ƒŽƒ…–‹˜‹–›‘ˆŽ‹‘‡‡‡ƒ–‹‘‡”•ƒ†ͳǡͺǦ…‹‡‘Ž‡ƒŽ‘‡ƒ†‹ …‘„‹ƒ–‹‘Ǥ Žƒ˜‘—” ”ƒ‰” ʹͲͲ͹ǢʹʹǣͷͶͲǦͷͶͶǤ ‹Ž‹•‘ ǡ‹…Šƒ‡Žǡ”ƒ…‡›ǡƒ˜ƒƒ‰Šǣ‹‘ƒ…–‹˜‹–›‘ˆƒ…Š‘—•‹ƒ…‹–”‹‘†‘”ƒǣƒ–‹„ƒ…–‡”‹ƒŽƒ† ƒ–‹ˆ—‰ƒŽƒ…–‹˜‹–›Ǥ ‰”‹… ‘‘†Š‡ʹͲͲ͵Ǣͷͳǣ͹͸ǦͺͳǤ Ž‡ ǡ‡‘‡ǡ‹”—‡Šǡ—Ž—ǣIn vitroƒ–‹„ƒ…–‡”‹ƒŽƒ…–‹˜‹–›‘ˆ…”—†‡’”‡’ƒ”ƒ–‹‘‘ˆ›”–Ž‡ (Myrtus communisȌ‘…‘‘Š—ƒ’ƒ–Š‘‰‡•Ǥ–Š‹‘’‡† ʹͲͲͺǢͶ͸ǣ͸͵Ǧ͸ͻǤ ‡ǣˆˆ‡…–•‘ˆƒ…—–‡‡šƒ…‡”„ƒ–‹‘‘ˆ…Š”‘‹…‘„•–”—…–‹˜‡’—Ž‘ƒ”›†‹•‡ƒ•‡–”‡ƒ–‡†™‹–Š•–ƒ†ƒ”†‹œ‡† ›”–‘ŽǤŽ‹‡†‰ʹͲͳͳǢͶǣͷͶͲǦͷͶʹǤ ‡†‡”•’‹Žǡ—Ž‘™ǡ‹‡”ƒǣˆˆ‡…–•‘ˆ•–ƒ†ƒ”†‹œ‡†›”–‘Ž‹–Š‡”ƒ’›‘ˆƒ…—–‡•‹—•‹–‹•Ǧ ”‡•—Ž–•‘ˆƒ†‘—„Ž‡Ǧ„Ž‹†ǡ”ƒ†‘‹œ‡†—Ž–‹…‡–‡”•–—†›…‘’ƒ”‡†™‹–Š’Žƒ…‡„‘Ǥƒ”›‰‘”Š‹‘‘–‘Ž‘‰‹‡ ͳͻͻ͹Ǣ͹͸ǣʹ͵Ǧʹ͹Ǥ •Š…”‘ˆ–ǡ‹’•‘ ǡ‹„”‡ŽŽǣ‹’Ž‡‡–Š‘†‘ˆ‡•–‹ƒ–‹‰•‡˜‡”‹–›‘ˆ’—Ž‘ƒ”›ϐ‹„”‘•‹•‘ƒ —‡”‹…ƒŽ•…ƒŽ‡Ǥ Ž‹ƒ–Š‘ŽͳͻͺͺǢͶͳǣͶ͸͹ǦͶ͹ͲǤ ƒ‰ƒ‘–‘ǡ‰—…Š‹ ǡ‡‡„‡ǣŽ’ŠƒǦ•‘‘–Š—•…Ž‡ƒ…–‹‡š’”‡••‹‘‹…—Ž–—”‡†Ž‡•‡’‹–Š‡Ž‹ƒŽ…‡ŽŽ•Ǥ ˜‡•–’Š–ŠƒŽ‘Ž‹•…‹ʹͲͲͲǢͶͳǣͳͳʹʹǦͳͳʹͻǤ ƒ‰‹‹ǡ‘”‘™‹–œ ǡ‘‘”‡ǡ‡‰‹ǡƒ”–‹‡œ ǡ‘‡™• ǡ–ƒ†‹ˆ‘”† ǡŠƒ‹…ƒŽ ǣ ‘†—Žƒ–‹‘‘ˆ’”‘•—”˜‹˜ƒŽ•‹‰ƒŽ‹‰‹ϐ‹„”‘„Žƒ•–•„›ƒ’”‘–‡‹‹ƒ•‡‹Š‹„‹–‘”’”‘–‡…–•ƒ‰ƒ‹•–ϐ‹„”‘–‹… –‹••—‡‹Œ—”›Ǥ ƒ–Š‘ŽʹͲͲͷǢͳ͸͸ǣ͵͸͹Ȃ͵͹ͷǤ ƒ˜‡ŽŽ‡ ǡ‹…Š‡Ž•‘ǡ‹‹–”‹Œ‡˜‹…ǣ‹‘Ž‘‰‹…ƒŽ’”‘–‡…–‹‘„›•—’‡”‘š‹†‡†‹•—–ƒ•‡Ǥ‹‘…Š‡‹‘’Š›• ‡•‘—ͳͻ͹͵Ǣͷͷǣ͵ͷͲȂ͵ͷ͹Ǥ ‹—Žƒǡ ƒ––ƒǡƒ ǡ—”›ǣš‹†ƒ–‹˜‡•–”‡••‹’—Ž‘ƒ”›ϐ‹„”‘•‹•Ǥ’‘••‹„Ž‡”‘Ž‡ˆ‘””‡†‘š ‘†—Žƒ–‘”›–Š‡”ƒ’›Ǥ ‡•’‹””‹–ƒ”‡‡†ʹͲͲͷǢͳ͹ʹǣͶͳ͹ǦͶʹʹǤ ƒ‡•ǡŠƒ†‹ǡ”‹–‹ ǡ ‡‹ƒǡ—…Š‹Šǡƒ†ƒ‘—‹ ǡ…Š‘—ǡƒ”œ‘—ǣ–‹‘š‹†ƒ– ƒ…–‹˜‹–‹‡•‘ˆ–Š‡‡••‡–‹ƒŽ‘‹Ž•ƒ†‡–Šƒ‘Ž‡š–”ƒ…–•ˆ”‘›”–Ž‡ȋmyrtus communis˜ƒ”Ǥ–ƒŽ‹…ƒŽǤȌŽ‡ƒˆǡ•–‡ ƒ†ϐŽ‘™‡”Ǥ ‘‘†Š‡‘š‹…‘ŽʹͲͳͲǢͶͺǣͳ͵͸ʹȂͳ͵͹ͲǤ ‡•‘—”ǡ‡†”ƒǡ„”‹‹ ǡ‘—Š†‹†ǡ±”‡œǦŽ˜ƒ”‡œ ǡ ‡”ž†‡œǦג‡œ ǣ‘–ƒŽ’Š‡‘Ž‹……‘–‡– ƒ†ƒ–‹‘š‹†ƒ–ƒ…–‹˜‹–›‘ˆ›”–Ž‡ȋmyrtus communisȌ‡š–”ƒ…–•Ǥƒ–”‘†‘—ʹͲͲͻǢͶǣͺͳͻǦͺʹͶǤ ‘•ƒǡ‡‹ƒƒǡƒ•—ǡ‘”‘ƒ ǡ’’‡†‹‘ ǡ‹ƒ…Š‹ ǡƒŽŽ‡”‘ǡ‡••¿ǣ–‹‘š‹†ƒ–ƒ…–‹˜‹–›‘ˆ oligomeric acylphloroglucinols from myrtus communisǤ ”‡‡ƒ†‹…‡•ʹͲͲ͵Ǣ͵͹ǣͳͲͳ͵ǦͳͲͳͻǤ Downloaded by: Univ of California San Diego 132.239.1.231 - 3/3/2017 8:59:18 AM Physiol Biochem 2016;38:619-634 Cellular Physiology Cell © 2016 The Author(s) Published by S Karger AG, Basel DOI: 10.1159/000438655 and Biochemistry Published online: February 08, 2016 www.karger.com/cpb 633 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 —‡ǡ‡‘Ž ǡ”ŠƒǣŠ‹„‹–‘”›’‘–‡–‹ƒŽ‘ˆ–Š‡Ž‡ƒ˜‡•ƒ†„‡””‹‡•‘ˆmyrtus communis l (myrtle) ƒ‰ƒ‹•–‡œ›‡•Ž‹‡†–‘‡—”‘†‡‰‡‡”ƒ–‹˜‡†‹•‡ƒ•‡•ƒ†–Š‡‹”ƒ–‹‘š‹†ƒ–ƒ…–‹‘•Ǥ–  ‘‘†…‹—–” ʹͲͳʹǢ͸͵ǣ͵ͺ͹Ǧ͵ͻʹǤ ƒ”†‡Ž‹ǡƒ••‹Ž‹‹ǡ–Šƒƒ•‹‘•ǡ‹„‘—”‹•ǡ‘ƒ‹–‹•ǣ••‡–‹ƒŽ‘‹Ž…‘’‘•‹–‹‘‘ˆPistacia lentiscus L and Myrtus communis L.ǣ˜ƒŽ—ƒ–‹‘‘ˆƒ–‹‘š‹†ƒ–…ƒ’ƒ…‹–›‘ˆ‡–Šƒ‘Ž‹…‡š–”ƒ…–•Ǥ ‘‘†Š‡ ʹͲͲͺǢͳͲ͹ǣͳͳʹͲȂͳͳ͵ͲǤ ‡Žǡ–‡™ƒ”– ǡ‡ŽŽ‡‰”‹‹ǣ”‡˜‹‡™‘ˆ”‡…‡–•–—†‹‡•‘ƒŽ‘†‹ƒŽ†‡Š›†‡ƒ•–‘š‹…‘Ž‡…—Ž‡ƒ† „‹‘Ž‘‰‹…ƒŽƒ”‡”‘ˆ‘š‹†ƒ–‹˜‡•–”‡••Ǥ—–”‡–ƒ„ƒ”†‹‘˜ƒ•…‹•ʹͲͲͷǢͳͷǣ͵ͳ͸Ȃ͵ʹͺǤ ……‘”† ǡ ”‹†‘˜‹…Šǣ—’‡”‘š‹†‡†‹•—–ƒ•‡Ǥ‡œ›‹…ˆ—…–‹‘ˆ‘”‡”›–Š”‘…—’”‡‹ȋŠ‡‘…—’”‡‹ȌǤ  ‹‘ŽŠ‡ͳͻ͸ͻǢʹͶͶǣ͸ͲͶͻǦ͸ͲͷͷǤ ……‘”† ǡ ”‹†‘˜‹…ŠǣŠ‡—–‹Ž‹–›‘ˆ•—’‡”‘š‹†‡†‹•—–ƒ•‡‹•–—†›‹‰ˆ”‡‡”ƒ†‹…ƒŽ”‡ƒ…–‹‘•Ǥ ‹‘ŽŠ‡ ͳͻ͸ͻǢʹͶͶǣ͸Ͳͷ͸Ǧ͸Ͳ͸͵Ǥ ƒ›†‡”ǡ„†‡Ž™ƒŠ‡†ǡ‹Žƒ‹ǡƒ”ǡƒŠ‘—†ǡ Š‡†‹”ƒǡŠ‡‹”Ǧ Š‡†‹”ƒǣ–‹Ǧ ‰‡‘–‘š‹…ƒ†ˆ”‡‡Ǧ”ƒ†‹…ƒŽ•…ƒ˜‡‰‹‰ƒ…–‹˜‹–‹‡•‘ˆ‡š–”ƒ…–•ˆ”‘ȋ–—‹•‹ƒȌmyrtus communisǤ—–ƒ–‡• ʹͲͲͶǢͷ͸ͶǣͺͻȂͻͷǤ ‘ƒ‹ǡ‘‹—ǡƒ”–ƒǡ‹‡ŽŽ‹ǡ ƒŽƒ”†‹ǡ‹…‹‡”‹ ǡ ”ƒ…‘‹ ǣ˜ƒŽ—ƒ–‹‘‘ˆƒ–‹‘š‹†ƒ–‡ˆˆ‡…–‘ˆ †‹ˆˆ‡”‡–‡š–”ƒ…–•‘ˆmyrtus communisǤ ”‡‡ƒ†‹…‡•ʹͲͲͻǢ͵ͺǣͻ͹ǦͳͲ͵ȋͳͲ͹ȌǤ –‘‡ŽŽƒǡ‘‹…ƒǡ‹˜‹ƒƒǡ ‹—Ž‹ƒǡ ‹‘˜ƒ‹ǡ ‡†‡”‹…ƒǡƒ—”‘ǡ••—–ƒǣ–‹‘š‹†ƒ– activity of oligomeric acylphloroglucinols from myrtus communisǤ ”‡‡ƒ†‹…‡•ʹͲͲ͵Ǣ͵͹ǣͳͲͳ͵ǦͳͲͳͻǤ ’’‡†‹‘ ǡ‹ƒ…Š‹ ǡ‹ƒ••‹ǡ–‡”‡”ǡƒŽŽ‡”‘ǡ ‹„„‘•ǣŽ‹‰‘‡”‹…ƒ…›Ž’ŠŽ‘”‘‰Ž—…‹‘Ž•ˆ”‘ myrtle (Myrtus communisȌǤ ƒ–”‘†ʹͲͲʹǢ͸ͷǣ͵͵ͶǦ͵͵ͺǤ Žƒƒ‹ǡ‘••—ǣƒ†‹…ƒŽ•…ƒ˜‡‰‹‰ƒ…–‹˜‹–›ƒ†ƒ–‹‘š‹†ƒ–ƒ…–‹˜‹–›‘ˆŽ‹“—‘”•‘ˆ›””–Š‡ȋMyrtus communis l.Ȍ„‡””‹‡•ƒ†Ž‡ƒ˜‡•Ǥ–ƒŽ  ‘‘†…‹ʹͲͲͶǢͳ͸ǣͳͻ͹ǦʹͲͺǤ ‘–‘”‘ǡ—„‡”‘•‘ ǡ‹ƒ…‡–‡ǡ‡””‘‡ǡ‡ ‡‘ǡƒ„”ƒ•ǡ‹œœƒǣ–ƒ„‹Ž‹–›ƒ†ƒ–‹‘š‹†ƒ– ƒ…–‹˜‹–›‘ˆ’‘Ž›’Š‡‘Ž•‹‡š–”ƒ…–•‘ˆMyrtus communis L.„‡””‹‡•—•‡†ˆ‘”–Š‡’”‡’ƒ”ƒ–‹‘‘ˆ›”–Ž‡Ž‹“—‡—”Ǥ Šƒ”‹‘‡†ƒŽʹͲͲ͸ǢͶͳǣͳ͸ͳͶǦͳ͸ͳͻǤ ‹ˆˆǡ‹„”‹…ǡ”‡•‡”ǡ ”‹„‡–œ ǣš…”‡–‹‘‘ˆŠ›†”‘š›’”‘Ž‹‡‹’ƒ–‹‡–•™‹–Š”Š‡—ƒ–‹…ƒ†‘Ǧ ”Š‡—ƒ–‹…†‹•‡ƒ•‡•Ǥ Ž‹˜‡•–ͳͻͷ͸Ǣ͵ͷǣͷ͹ͻǦͷͺ͹Ǥ ‹”‹ǡ›†‡ǡ‘ŽŽ‹‰‡”ǣˆˆ‡…–‘ˆƒ–‹„‘†›–‘–”ƒ•ˆ‘”‹‰‰”‘™–Šˆƒ…–‘”„‡–ƒ‘„Ž‡‘›…‹ ‹†—…‡†ƒ……——Žƒ–‹‘‘ˆŽ—‰…‘ŽŽƒ‰‡‹‹…‡ǤŠ‘”ƒ…ͳͻͻ͵ǢͶͺǣͻͷͻǦͻ͸͸Ǥ ”‘‡‡Žƒ ǡ‹’‡”ǡ‘Ž„›ǡƒŽ† ǣ”ƒ•ˆ‘”‹‰‰”‘™–Šˆƒ…–‘”„‡–ƒͳ‹•’”‡•‡–ƒ–•‹–‡•‘ˆ ‡š–”ƒ…‡ŽŽ—Žƒ”ƒ–”‹š‰‡‡‡š’”‡••‹‘‹Š—ƒ’—Ž‘ƒ”›ϐ‹„”‘•‹•Ǥ”‘…ƒ–Ž…ƒ†…‹ͳͻͻͳǢͺͺǣ͸͸ͶʹǦ ͸͸Ͷ͸Ǥ ‹ŽŽ‹•ǡ‘”‘ǣ‰ˆǦ„‡–ƒǦ‹†—…‡†‡–Ǥ‡…Šƒ‹••ƒ†‹’Ž‹…ƒ–‹‘•ˆ‘”ϐ‹„”‘–‹…Ž—‰†‹•‡ƒ•‡Ǥ  Š›•‹‘Ž—‰‡ŽŽ‘ŽŠ›•‹‘ŽʹͲͲ͹Ǣʹͻ͵ǣͷʹͷǦͷ͵ͶǤ ƒ‰ ǡƒ‘ǡ—ǡ‹—ǡƒǡ‡‰ǡ —‘ǣ–‡”Ž‡—‹ǦͳȾ”‘‘–‡•’‹–Š‡Ž‹ƒŽǦ‡”‹˜‡†Ž˜‡‘Žƒ” Žƒ•–‘‰‡‡•‹•˜‹ƒȽ˜Ⱦ͸–‡‰”‹Ǧ‡’‡†‡– ǦȾ…–‹˜ƒ–‹‘Ǥ‡ŽŽŠ›•‹‘Ž‹‘…Š‡ǤʹͲͳͷǢ͵͸ǣʹͳͻͺǦʹʹͳ͸Ǥ ‹‰ǡ‹ƒ‘ǡ— ǡŠ‘— ǡ‘‰ǡ—‘ ǣ‰ˆǦ„‡–ƒͳ‹•‡”—ƒ†‹†—…‡†•’—–—ˆ‘”’”‡†‹…–‹‰ radiation pneumonitis in patients with non-small cell lung cancer after radiotherapy Chin J Cancer ʹͲͳͲǢʹͻǣ͵ͷ͵Ǧ͵ͷͺǤ ”ƒ…‡› ǡ‡”ƒ‹ǣ—‘”‡…”‘•‹•ˆƒ…–‘”ǣƒ’Ž‡‹‘–”‘’‹……›–‘‹‡ƒ†–Š‡”ƒ’—‡–‹…–ƒ”‰‡–Ǥ—‡˜‡† ͳͻͻͶǢͶͷǣͶͻͳǦͷͲ͵Ǥ Š‹‡Š ǡ•ƒ‹ ǡ•‘— ǡ—ǣͳ”‡‰—Žƒ–‹‘‹Š—ƒ’—Ž‘ƒ”›‡’‹–Š‡Ž‹ƒŽ…‡ŽŽ•„›–—‘”‡…”‘•‹• ˆƒ…–‘”Ǥ‡ŽŽŠ›•‹‘Ž‹‘…Š‡ʹͲͳͶǢ͵Ͷǣͳ͵͹͵Ǧͳ͵ͺͶǤ ƒŽ…‡™‹…œǦƒ„Ž‹•ƒǡ‡ƒ‡ ǡ‘”ˆ‡Ž†ǡ‡‘Ž† ǣƒ–Š‘‰‡‹…›…‘„ƒ…–‡”‹—–—„‡”…—Ž‘•‹•‡˜ƒ†‡• ƒ’‘’–‘•‹•‘ˆŠ‘•–ƒ…”‘’Šƒ‰‡•„›”‡Ž‡ƒ•‡‘ˆ–ˆǦ”ʹǡ”‡•—Ž–‹‰‹‹ƒ…–‹˜ƒ–‹‘‘ˆ–ˆǦƒŽ’ŠƒǤ —‘Ž ͳͻͻͺǢͳ͸ͳǣʹ͸͵͸Ǧʹ͸ͶͳǤ ‘‰ǡƒ‰ ǡ‹—ǡŠ‡ǡŠ‡ǡŠ‡ ǡ‡ ǡ‹ǡƒ ǣ‘†—Žƒ–‹‘‘ˆ”ƒ†‹ƒ–‹‘Ǧ‹†—…‡† –—‘—”‡…”‘•‹•ˆƒ…–‘”ǦȽƒ†–”ƒ•ˆ‘”‹‰‰”‘™–Šˆƒ…–‘”Ⱦͳ‡š’”‡••‹‘‹–Š‡Ž—‰–‹••—‡„›•Š‡‰“‹ ˆ—œŠ‡‰‹Œ‡…–‹‘Ǥ‘Ž‡†‡’ʹͲͳͲǢ͵ǣ͸ʹͳǦ͸ʹ͹ȋ͸ʹ͹ȌǤ ‹Šƒǡƒ‰ ǡ—‹…Ž‹ˆˆ‡ǡ ‘‰ǡ‹‡”ƒǣ›–‘‹‡‰‡‡’‘Ž›‘”’Š‹••‹‹†‹‘’ƒ–Š‹… ’—Ž‘ƒ”›ϐ‹„”‘•‹•Ǥ–”‡‡† ʹͲͲͶǢ͵Ͷǣͳʹ͸ǦͳʹͻǤ Downloaded by: Univ of California San Diego 132.239.1.231 - 3/3/2017 8:59:18 AM Zhao et al.: Myrtol Standardized on Radiation-Induced Lung Injury Physiol Biochem 2016;38:619-634 Cellular Physiology Cell © 2016 The Author(s) Published by S Karger AG, Basel DOI: 10.1159/000438655 and Biochemistry Published online: February 08, 2016 www.karger.com/cpb 634 Zhao et al.: Myrtol Standardized on Radiation-Induced Lung Injury 48 49 50 51 52 53 54 55 56 57 58 Š›–‡ǡ—„„ƒ”†ǡǡŠ‹†„‘”‡ǡƒ–‘ǡ‹‰Ž‡ǡ‹• ǡ—ˆˆ ǡ ƒ……Š‹‹ǡƒ…‹ŽŽ‹ǡ ƒ„„”‹ǣ …”‡ƒ•‡†”‹•‘ˆϐ‹„”‘•‹‰ƒŽ˜‡‘Ž‹–‹•ƒ••‘…‹ƒ–‡†™‹–Š‹–‡”Ž‡—‹Ǧͳ”‡…‡’–‘”ƒ–ƒ‰‘‹•–ƒ†–—‘”‡…”‘•‹• ˆƒ…–‘”ǦƒŽ’Šƒ‰‡‡’‘Ž›‘”’Š‹••Ǥ ‡•’‹””‹–ƒ”‡‡†ʹͲͲͲǢͳ͸ʹǣ͹ͷͷǦ͹ͷͺǤ ‡‹•ǣ–‡”Ž‡—‹Ǧ͸‹‘—•‡Š›’‡”•‡•‹–‹˜‹–›’‡—‘‹–‹•ǣ…Šƒ‰‡•‹Ž—‰ˆ”‡‡…‡ŽŽ•ˆ‘ŽŽ‘™‹‰ †‡’Ž‡–‹‘‘ˆ‡†‘‰‡‘—•‹ŽǦ͸‘”†‹”‡…–ƒ†‹‹•–”ƒ–‹‘‘ˆ‹ŽǦ͸Ǥ ‡—‘…‹‘ŽͳͻͻʹǢͷʹǣͳͻ͹ǦʹͲͳǤ —Š…Š›ƒ—ǡŽŽ‹˜‹‡”ǡ ƒ…“—‡Ž‹‡ǡƒ—ŽǡŠ‡”‡•‡ǡŠ‹Ž‹’ǣ–‡”Ž‡—‹ȋ‹ŽȌǦͳƒƒ†‹ŽǦ͸Ǥ’’Ž‹…ƒ–‹‘•–‘ –Š‡’”‡†‹…–‹˜‡†‹ƒ‰‘•–‹…–‡•–‹‰‘ˆ”ƒ†‹ƒ–‹‘’‡—‘‹–‹•Ǥ– ƒ†‹ƒ–…‘Ž‹‘ŽŠ›•ʹͲͲͷǢ͸ʹǣʹ͸ͲǦʹ͸͸Ǥ ƒ—Ž†‹‡ ǡ‘Ž„ǡ‹‡ ǣ‡™†‹”‡…–‹‘‹–Š‡’ƒ–Š‘‰‡‡•‹•‘ˆ‹†‹‘’ƒ–Š‹…’—Ž‘ƒ”›ϐ‹„”‘•‹•ǫ‡•’‹” ‡•ʹͲͲʹǢ͵ǣͳǦ͵Ǥ ƒ…Š‡”‹ǡƒ•–”—œœ‘ǡ‘”–‹‘ǡ”‹‹ǣŠ‡Ž—‰ƒ•ƒ’”‹˜‹Ž‡‰‡†•‹–‡ˆ‘”–Š‡„‡‡ϐ‹…‹ƒŽƒ…–‹‘•‘ˆ ’‰‡ʹǤ”‡†•—‘ŽʹͲͲͶǢʹͷǣͶͲȂͶ͸Ǥ Žƒǣ’‹–Š‡Ž‹ƒŽ…‡ŽŽ‘†—Žƒ–‹‘‘ˆƒ‹”™ƒ›ϐ‹„”‘•‹•‹ƒ•–ŠƒǤ ‡•’‹”‡ŽŽ‘Ž‹‘ŽʹͲͲ͵ǢʹͺǣͳʹͷǦ ͳʹͺǤ ”‡‡Ž‡‡ ǡ‡”„ǡŠ‡”ƒ†ƒ† ǣƒ–”‹š‡–ƒŽŽ‘’”‘–‡‹ƒ•‡•‹Ž—‰ǣ—Ž–‹’Ž‡ǡ—Ž–‹ˆƒ”‹‘—•ǡƒ† —Ž–‹ˆƒ…‡–‡†ǤŠ›•‹‘Ž‡˜ʹͲͲ͹Ǣͺ͹ǣ͸ͻǦͻͺǤ ƒ‰ǡ‘‰ ǡ—ǡ‡ǡ—ǡ—ǡ ‹ƒ‰ǡŠƒ‰ǣ‹‰Š‰Ž—…‘•‡’”‘‘–‡•–—‘”‹˜ƒ•‹‘ƒ† ‹…”‡ƒ•‡•‡–ƒ•–ƒ•‹•Ǧƒ••‘…‹ƒ–‡†’”‘–‡‹‡š’”‡••‹‘‹Š—ƒŽ—‰‡’‹–Š‡Ž‹ƒŽ…‡ŽŽ•„›—’”‡‰—Žƒ–‹‰ Š‡‡‘š›‰‡ƒ•‡Ǧͳ˜‹ƒ”‡ƒ…–‹˜‡‘š›‰‡•’‡…‹‡•‘”–Š‡ ǦȾͳȀ͵Ȁ–•‹‰ƒŽ‹‰’ƒ–Š™ƒ›Ǥ‡ŽŽŠ›•‹‘Ž ‹‘…Š‡ǤʹͲͳͷǢ͵ͷǣͳͲͲͺǦͳͲʹʹǤ Šƒ”ƒ„ƒ”–‹ǡƒ–‡Žǣƒ–”‹š‡–ƒŽŽ‘’”‘–‡‹ƒ•‡Ǧʹȋ’ǦʹȌƒ†’Ǧͻ‹’—Ž‘ƒ”›’ƒ–Š‘Ž‘‰›Ǥš’ —‰‡•ʹͲͲͷǢ͵ͳǣͷͻͻǦ͸ʹͳǤ ‡Žƒǡ‹‰ǡƒ”†‘ǣ†‹‘’ƒ–Š‹…’—Ž‘ƒ”›ϐ‹„”‘•‹•Ǥ”‡˜ƒ‹Ž‹‰ƒ†‡˜‘Ž˜‹‰Š›’‘–Š‡•‡•ƒ„‘—–‹–• ’ƒ–Š‘‰‡‡•‹•ƒ†‹’Ž‹…ƒ–‹‘•ˆ‘”–Š‡”ƒ’›Ǥ–‡”‡†ʹͲͲͳǢͳ͵Ͷǣͳ͵͸ǦͳͷͳǤ ‘”„‡Žǡƒ—Ž‡–Ǧƒ—‰‡†”‡ǡ ‡”ƒ‹ǡ‘Ž‡–ǡƒ‰‡–‡ǡ‘‹…Š‘–ǣŠ‹„‹–‹‘‘ˆ„Ž‡‘›…‹Ǧ‹†—…‡† ’—Ž‘ƒ”›ϐ‹„”‘•‹•‹‹…‡„›–Š‡ƒ–”‹š‡–ƒŽŽ‘’”‘–‡‹ƒ•‡‹Š‹„‹–‘”„ƒ–‹ƒ•–ƒ–Ǥ ƒ–Š‘ŽʹͲͲͳǢͳͻ͵ǣͷ͵ͺǦ ͷͶͷǤ —‰ƒǡ›‘ƒ‰ƒǡƒ‘–‘ǡ —•Š‹ƒǡ‹›ƒƒ™ƒǡƒ‹‡ǡ†‘ǣŠƒ”ƒ…–‡”‹•–‹…‡Ž‡˜ƒ–‹‘ ‘ˆƒ–”‹š‡–ƒŽŽ‘’”‘–‡‹ƒ•‡ƒ…–‹˜‹–›‹‹†‹‘’ƒ–Š‹…‹–‡”•–‹–‹ƒŽ’‡—‘‹ƒ•Ǥ ‡•’‹””‹–ƒ”‡‡† ʹͲͲͲǢͳ͸ʹǣͳͻͶͻǦͳͻͷ͸Ǥ Downloaded by: Univ of California San Diego 132.239.1.231 - 3/3/2017 8:59:18 AM 47 ... model of radiationinduced lung injury was generated by using thoracic irradiation with a single dose of 16Gy Mice were orally administrated with Myrtol (25 mg/kg/day) for weeks after irradiation,... 7UHDWPHQWZLWK0\UWROVWDQGDUGL]HGEXWQRWSUHGQLVRQHUHGXFHGOXQJFRHIÀFLHQWDQGFROODJHQ deposition in lung tissues, while attenuated histological damages induced by irradiation Myrtol standardized also reduced the production of MDA, while increased the level of SOD It ZDVDOVRREVHUYHGWKDW0\UWROVWDQGDUGL]HGLQKLELWHG7*)DŽDQGDVHULHVRISURLQÁDPPDWRU\... DOYHROL after a single dose of 16Gy Conclusion: The present results suggest Myrtol standardized as an effective agent for attenuating the lung injury induced by irradiation © 2016 The Author(s)