Markers of oxidative/nitrosative stress and inflammation in lung tissue of rats exposed to different intravenous iron compounds
Jorge E Toblli,1 Gabriel Cao,1 Jorge F Giani,2 Fernando P Dominici,2 Margarita Angerosa1 1Laboratory of Experimental Medicine, Hospital Alemán, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina; 2Department of Biochemistry, School of Pharmacy, Institute of Chemistry...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2017-08-01
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| Series: | Drug Design, Development and Therapy |
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| Online Access: | https://www.dovepress.com/markers-of-oxidativenitrosative-stress-and-inflammation-in-lung-tissue-peer-reviewed-article-DDDT |
| _version_ | 1819083675668578304 |
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| author | Toblli JE Cao G Giani JF Dominici FP Angerosa M |
| author_facet | Toblli JE Cao G Giani JF Dominici FP Angerosa M |
| author_sort | Toblli JE |
| collection | DOAJ |
| description | Jorge E Toblli,1 Gabriel Cao,1 Jorge F Giani,2 Fernando P Dominici,2 Margarita Angerosa1 1Laboratory of Experimental Medicine, Hospital Alemán, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina; 2Department of Biochemistry, School of Pharmacy, Institute of Chemistry and Biophysics-Biochemistry (UBA-CONICET), Buenos Aires, Argentina Abstract: Iron deficiency anemia is a frequent complication in clinical conditions such as chronic kidney disease, chronic heart failure, inflammatory bowel disease, cancer, and excessive blood loss. Given the ability of iron to catalyze redox reactions, iron therapy can be associated with oxidative stress. The lung is uniquely susceptible to oxidative stress, and little is known about the effects of intravenous iron treatment in this organ. This study characterized changes in markers of oxidative/nitrosative stress and inflammation in the lung of non-iron deficient, non-anemic rats treated with five weekly doses (40 mg iron per kg body weight) of low molecular weight iron dextran (LMWID), iron sucrose (IS), ferric carboxymaltose (FCM), ferumoxytol (FMX), iron isomaltoside 1000 (IIM), or saline (control). Rats treated with LMWID, FMX, or IIM showed significant changes in most measures of oxidative/nitrosative stress, inflammation, and iron deposition compared to the saline-treated controls, with greatest changes in the LMWID treatment group. Increases in products of lipid peroxidation (thiobarbituric acid reactive substances) and protein nitrosation (nitrotyrosine) were consistent with increases in the activity of antioxidant enzymes (catalase, Cu,Zn-SOD, GPx), decreases in antioxidative capacity (reduced:oxidized GSH ratio), increased levels of transcription factors involved in the inflammatory pathway (NF-κB, HIF-1α), inflammatory cytokines (TNF-α, IL-6), adhesion molecules (VCAM-1), markers of macrophage infiltration (ED-1), and iron deposition (Prussian blue, ferritin). Since changes in measured parameters in FCM- or IS-treated rats were generally modest, the results suggest that FCM and IS have a low propensity to induce lung inflammation. The relevance of these findings to clinical safety profiles of the tested intravenous iron products requires further investigation. Keywords: intravenous iron, oxidative stress, nitrosative stress, inflammation, lung, rodent model |
| first_indexed | 2024-12-21T20:36:20Z |
| format | Article |
| id | doaj.art-d2ee1f2f59ae46fd92f99505da4fd3ab |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-12-21T20:36:20Z |
| publishDate | 2017-08-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-d2ee1f2f59ae46fd92f99505da4fd3ab2022-12-21T18:51:06ZengDove Medical PressDrug Design, Development and Therapy1177-88812017-08-01Volume 112251226334052Markers of oxidative/nitrosative stress and inflammation in lung tissue of rats exposed to different intravenous iron compoundsToblli JECao GGiani JFDominici FPAngerosa MJorge E Toblli,1 Gabriel Cao,1 Jorge F Giani,2 Fernando P Dominici,2 Margarita Angerosa1 1Laboratory of Experimental Medicine, Hospital Alemán, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina; 2Department of Biochemistry, School of Pharmacy, Institute of Chemistry and Biophysics-Biochemistry (UBA-CONICET), Buenos Aires, Argentina Abstract: Iron deficiency anemia is a frequent complication in clinical conditions such as chronic kidney disease, chronic heart failure, inflammatory bowel disease, cancer, and excessive blood loss. Given the ability of iron to catalyze redox reactions, iron therapy can be associated with oxidative stress. The lung is uniquely susceptible to oxidative stress, and little is known about the effects of intravenous iron treatment in this organ. This study characterized changes in markers of oxidative/nitrosative stress and inflammation in the lung of non-iron deficient, non-anemic rats treated with five weekly doses (40 mg iron per kg body weight) of low molecular weight iron dextran (LMWID), iron sucrose (IS), ferric carboxymaltose (FCM), ferumoxytol (FMX), iron isomaltoside 1000 (IIM), or saline (control). Rats treated with LMWID, FMX, or IIM showed significant changes in most measures of oxidative/nitrosative stress, inflammation, and iron deposition compared to the saline-treated controls, with greatest changes in the LMWID treatment group. Increases in products of lipid peroxidation (thiobarbituric acid reactive substances) and protein nitrosation (nitrotyrosine) were consistent with increases in the activity of antioxidant enzymes (catalase, Cu,Zn-SOD, GPx), decreases in antioxidative capacity (reduced:oxidized GSH ratio), increased levels of transcription factors involved in the inflammatory pathway (NF-κB, HIF-1α), inflammatory cytokines (TNF-α, IL-6), adhesion molecules (VCAM-1), markers of macrophage infiltration (ED-1), and iron deposition (Prussian blue, ferritin). Since changes in measured parameters in FCM- or IS-treated rats were generally modest, the results suggest that FCM and IS have a low propensity to induce lung inflammation. The relevance of these findings to clinical safety profiles of the tested intravenous iron products requires further investigation. Keywords: intravenous iron, oxidative stress, nitrosative stress, inflammation, lung, rodent modelhttps://www.dovepress.com/markers-of-oxidativenitrosative-stress-and-inflammation-in-lung-tissue-peer-reviewed-article-DDDTintravenous ironoxidative stressnitrosative stressinflammationlungrodent model |
| spellingShingle | Toblli JE Cao G Giani JF Dominici FP Angerosa M Markers of oxidative/nitrosative stress and inflammation in lung tissue of rats exposed to different intravenous iron compounds Drug Design, Development and Therapy intravenous iron oxidative stress nitrosative stress inflammation lung rodent model |
| title | Markers of oxidative/nitrosative stress and inflammation in lung tissue of rats exposed to different intravenous iron compounds |
| title_full | Markers of oxidative/nitrosative stress and inflammation in lung tissue of rats exposed to different intravenous iron compounds |
| title_fullStr | Markers of oxidative/nitrosative stress and inflammation in lung tissue of rats exposed to different intravenous iron compounds |
| title_full_unstemmed | Markers of oxidative/nitrosative stress and inflammation in lung tissue of rats exposed to different intravenous iron compounds |
| title_short | Markers of oxidative/nitrosative stress and inflammation in lung tissue of rats exposed to different intravenous iron compounds |
| title_sort | markers of oxidative nitrosative stress and inflammation in lung tissue of rats exposed to different intravenous iron compounds |
| topic | intravenous iron oxidative stress nitrosative stress inflammation lung rodent model |
| url | https://www.dovepress.com/markers-of-oxidativenitrosative-stress-and-inflammation-in-lung-tissue-peer-reviewed-article-DDDT |
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