{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T23:07:12Z","timestamp":1774998432200,"version":"3.50.1"},"reference-count":36,"publisher":"FapUNIFESP (SciELO)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. bras. pneumol."],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:p> Objective : To investigate the effects of N-acetylcysteine (NAC) and pentoxifylline in a model of remote organ injury after hind-limb ischemia\/reperfusion (I\/R) in rats, the lungs being the remote organ system.  Methods : Thirty-five male Wistar rats were assigned to one of five conditions (n = 7\/group), as follows: sham operation (control group); hind-limb ischemia, induced by clamping the left femoral artery, for 2 h, followed by 24 h of reperfusion (I\/R group); and hind-limb ischemia, as above, followed by intraperitoneal injection (prior to reperfusion) of 150 mg\/kg of NAC (I\/R+NAC group), 40 mg\/kg of pentoxifylline (I\/R+PTX group), or both (I\/R+NAC+PTX group). At the end of the trial, lung tissues were removed for histological analysis and assessment of oxidative stress.  Results : In comparison with the rats in the other groups, those in the I\/R group showed lower superoxide dismutase activity and glutathione levels, together with higher malondialdehyde levels and lung injury scores (p &lt; 0.05 for all). Interstitial inflammatory cell infiltration of the lungs was also markedly greater in the I\/R group than in the other groups. In addition, I\/R group rats showed various signs of interstitial edema and hemorrhage. In the I\/R+NAC, I\/R+PTX, and I\/R+NAC+PTX groups, superoxide dismutase activity, glutathione levels, malondialdehyde levels, and lung injury scores were preserved (p &lt; 0.05 for all). The differences between the administration of NAC or pentoxifylline alone and the administration of the two together were not significant for any of those parameters (p &gt; 0.05 for all).  Conclusions : Our results suggest that NAC and pentoxifylline both protect lung tissue from the effects of skeletal muscle I\/R. However, their combined use does not appear to increase the level of that protection.<\/jats:p>","DOI":"10.1590\/s1806-37562016000000183","type":"journal-article","created":{"date-parts":[[2016,3,21]],"date-time":"2016-03-21T11:22:20Z","timestamp":1458559340000},"page":"9-14","source":"Crossref","is-referenced-by-count":27,"title":["Effects of N-acetylcysteine and pentoxifylline on remote lung injury in a rat model of hind-limb ischemia\/reperfusion injury"],"prefix":"10.1590","volume":"42","author":[{"given":"Hamed Ashrafzadeh","family":"Takhtfooladi","sequence":"first","affiliation":[{"name":"Islamic Azad University,  Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saeed","family":"Hesaraki","sequence":"additional","affiliation":[{"name":"Islamic Azad University,  Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Foad","family":"Razmara","sequence":"additional","affiliation":[{"name":"Novin Pet Clinic,  Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad Ashrafzadeh","family":"Takhtfooladi","sequence":"additional","affiliation":[{"name":"Islamic Azad University,  Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hadi","family":"Hajizadeh","sequence":"additional","affiliation":[{"name":"Islamic Azad University,  Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"530","reference":[{"issue":"2","key":"ref1","doi-asserted-by":"crossref","first-page":"C227","DOI":"10.1152\/ajpcell.00112.2001","article-title":"Reactive species mechanisms of cellular hypoxia-reoxygenation injury","volume":"282","author":"Li C","year":"2002","journal-title":"Am J Physiol Cell Physiol"},{"issue":"1","key":"ref2","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s00268-001-0169-2","article-title":"Lower limb ischemia-reperfusion injury triggers a systemic inflammatory response and multiple organ dysfunction","volume":"26","author":"Yassin MM","year":"2002","journal-title":"World J Surg"},{"issue":"5","key":"ref3","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/S1078-5884(97)80284-5","article-title":"The inflammatory response to vascular surgery-associated ischaemia and reperfusion in man: effect on postoperative pulmonary function","volume":"14","author":"Groeneveld AB","year":"1997","journal-title":"Eur J Vasc Endovasc Surg"},{"issue":"2","key":"ref4","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1097\/00000658-198902000-00015","article-title":"Noncardiogenic pulmonary edema after abdominal aortic aneurysm surgery","volume":"209","author":"Paterson IS","year":"1989","journal-title":"Ann Surg"},{"issue":"6","key":"ref5","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1002\/bjs.1800780607","article-title":"Pathophysiology of ischaemia reperfusion injury: central role of the neutrophil","volume":"78","author":"Welbourn CR","year":"1991","journal-title":"Br J Surg"},{"issue":"4","key":"ref6","first-page":"316","article-title":"Pulmonary failure following lower torso ischemia: clinical evidence for a remote effect of reperfusion injury","volume":"61","author":"Fantini GA","year":"1995","journal-title":"Am Surg"},{"issue":"1","key":"ref7","first-page":"30","article-title":"Melatonin attenuates lung injury in a hind limb ischemia-reperfusion rat model","volume":"21","author":"Takhtfooladi H","year":"2015","journal-title":"Rev Port Pneumol (2006)"},{"issue":"4","key":"ref8","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1590\/S1806-37132013000400006","article-title":"Effect of tramadol on lung injury induced by skeletal muscle ischemia-reperfusion: an experimental study","volume":"39","author":"Takhtfooladi MA","year":"2013","journal-title":"J Bras Pneumol"},{"issue":"2","key":"ref9","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1590\/S0102-86502012000200012","article-title":"Effect of N-acetylcysteine on lung injury induced by skeletal muscle ischemia-reperfusion. Histopathological study in rat model","volume":"27","author":"Sotoudeh A","year":"2012","journal-title":"Acta Cir Bras"},{"issue":"5","key":"ref10","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1093\/ndt\/gfk032","article-title":"N-acetylcysteine attenuates kidney injury in rats subjected to renal ischaemia reperfusion","volume":"21","author":"Nitescu N","year":"2006","journal-title":"Nephrol Dial Transplant"},{"issue":"9","key":"ref11","doi-asserted-by":"crossref","first-page":"829","DOI":"10.3109\/08860220903137509","article-title":"Pentoxifylline in ischemia-induced acute kidney injury in rats","volume":"31","author":"Okumura AS","year":"2009","journal-title":"Ren Fail"},{"issue":"3","key":"ref12","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1053\/j.ajkd.2008.05.012","article-title":"Effect of pentoxifylline in addition to losartan on proteinuria and GFR in CKD: A 12-month randomized trial","volume":"52","author":"Lin SL","year":"2008","journal-title":"Am J Kidney Dis"},{"issue":"1","key":"ref13","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/j.1600-079X.2005.00272.x","article-title":"Preventive effect of melatonin on bleomycin-induced lung fibrosis in rats","volume":"40","author":"Yildirim Z","year":"2006","journal-title":"J Pineal Res"},{"key":"ref14","series-title":"Free radicals in diagnostic medicine.A systems approach to laboratory technology, clinical correlations, and antioxidant therapy","first-page":"1","volume-title":"Lipid peroxides and related radicals in clinical medicine","author":"Yagi K","year":"1994"},{"issue":"2","key":"ref15","first-page":"337","article-title":"The estimation of red cell superoxide dismutase activity","volume":"85","author":"Winterbourn CC","year":"1975","journal-title":"J Lab Clin Med"},{"issue":"1","key":"ref16","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/0003-9861(59)90090-6","article-title":"Tissue sulfhydryl groups","volume":"82","author":"ELLMAN GL","year":"1959","journal-title":"Arch Biochem Biophys"},{"issue":"5","key":"ref17","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.phrs.2004.11.007","article-title":"Inhibition of poly(ADP-ribose) polymerase attenuates lung tissue damage after hind limb ischemia-reperfusion in rats","volume":"51","author":"Koksel O","year":"2005","journal-title":"Pharmacol Res"},{"issue":"9","key":"ref18","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1097\/00003246-199309000-00023","article-title":"Reperfusion injury after intestinal ischemia","volume":"21","author":"Schoenberg MH","year":"1993","journal-title":"Crit Care Med"},{"issue":"2","key":"ref19","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1046\/j.1440-1827.1999.00829.x","article-title":"Reactive oxygen species-induced molecular damage and its application in pathology","volume":"49","author":"Toyokuni S","year":"1999","journal-title":"Pathol Int"},{"key":"ref20","series-title":"Non-enzymatic antioxidant defense system.In Frei B, editor. Natural antioxidants in human health and disease","author":"Brivida K","year":"1994"},{"issue":"1-2","key":"ref21","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/S0891-5849(98)00196-8","article-title":"Biomarkers of free radical damage applications in experimental animals and in humans","volume":"26","author":"de Zwart LL","year":"1999","journal-title":"Free Radic Biol Med"},{"issue":"2","key":"ref22","doi-asserted-by":"crossref","first-page":"123","DOI":"10.2165\/00003088-199120020-00004","article-title":"Clinical pharmacokinetics of N-acetylcysteine","volume":"20","author":"Holdiness MR","year":"1991","journal-title":"Clin Pharmacokinet"},{"issue":"3","key":"ref23","doi-asserted-by":"crossref","first-page":"204","DOI":"10.5114\/pjp.2013.38140","article-title":"The antioxidant role of N-acetylcysteine on the testicular remote injury after skeletal muscle ischemia and reperfusion in rats","volume":"64","author":"Takhtfooladi MA","year":"2013","journal-title":"Pol J Pathol"},{"issue":"6","key":"ref24","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/0891-5849(89)90066-X","article-title":"The antioxidant action of N-acetylcysteine: its reaction with hydrogen peroxide, hydroxyl radical, superoxide, and hypochlorous acid","volume":"6","author":"Aruoma OI","year":"1989","journal-title":"Free Radic Biol Med"},{"issue":"3","key":"ref25","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/S0008-6363(00)00018-3","article-title":"Effects of n-acetylcysteine in a rat model of ischemia and reperfusion injury","volume":"47","author":"Cuzzocrea S","year":"2000","journal-title":"Cardiovasc Res"},{"issue":"1","key":"ref26","first-page":"75","article-title":"Protective effect of N-acetylcysteine on renal ischemia\/reperfusion injury in the rat","volume":"16","author":"Sehirli AO","year":"2003","journal-title":"J Nephrol"},{"issue":"3","key":"ref27","first-page":"292","article-title":"N-acetyl cysteine ameliorates ischemic renal failure","volume":"272","author":"DiMari J","year":"1997","journal-title":"Am J Physiol"},{"issue":"5","key":"ref28","first-page":"412","article-title":"Trimetazidine and N-acetylcysteine in attenuating hind-limb ischemia and reperfusion injuries: experimental study in rats","volume":"28","author":"Da Silveira M","year":"2009","journal-title":"Int Angiol"},{"issue":"10","key":"ref29","doi-asserted-by":"crossref","first-page":"3067","DOI":"10.1093\/ndt\/gfn237","article-title":"N-acetylcysteine protects against renal injury following bilateral ureteral obstruction","volume":"23","author":"Shimizu MH","year":"2008","journal-title":"Nephrol Dial Transplant"},{"issue":"1","key":"ref30","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1177\/108925320500900107","article-title":"Evidence-based renal protection in cardiac surgery","volume":"9","author":"Stafford-Smith M","year":"2005","journal-title":"Semin Cardiothorac Vasc Anesth"},{"issue":"7","key":"ref31","first-page":"295","article-title":"Effects of lloprost and pentoxifylline on renal ischemia-reperfusion in rabbit model","volume":"11","author":"Emrecan B","year":"2006","journal-title":"Eur J Med Res"},{"issue":"4","key":"ref32","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1080\/154386090897974","article-title":"Pentoxifylline diminishes the oxidative damage to renal tissue induced by streptozotocin in the rat","volume":"5","author":"D\u00e1vila-Esqueda ME","year":"2004","journal-title":"Exp Diabesity Res"},{"issue":"6","key":"ref33","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1081\/JDI-200038329","article-title":"The effects of pentoxifylline on diabetic renal changes in streptozotocin-induced diabetes mellitus","volume":"26","author":"Gunduz Z","year":"2004","journal-title":"Ren Fail"},{"issue":"3","key":"ref34","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/ki.1989.218","article-title":"Effects of 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