title: Nitric oxide: a new biomarker of Doxorubicin toxicity in children?
abstract: Doxorubicin (DOX) has been used in the treatment of childhood cancers, but its usage is limited because of cardiotoxicity. There are many studies on the role of nitric oxide (NO) in several cardiac diseases. However, to the authors' knowledge, no studies have investigated the plasma levels of total nitrite, a stable product of NO, in children that received DOX. The authors determined plasma total nitrite levels in 29 children who received DOX and investigated the correlations between these and other clinical and laboratory findings. All patients were in remission during the study period. Plasma total nitrite levels and cardiac functions were determined prospectively. The mean cumulative DOX dose was 310.0 ± 90.9 mg/m(2). In echocardiographic evaluation, 3 patients (10.3%) had a pathological value for ejection fraction (EF) and/or fractional shortening (FS), whereas 11 patients (37.9%) had a threshold value. Total nitrite levels were higher in patients than in matched controls (75.24 ± 39.4 vs 43.14 ± 10.58 μmol/L, respectively, P < .001). It was also found to be higher in patients who had a pathological/threshold value of EF and FS than in patients who had a physiological value of EF and FS (92.35 ± 50.36 vs 59.26 ± 13.56 μmol/L, respectively, P = .038). A negative correlation was found between FS and plasma total nitrite level (r = -.42, P = .023). The authors speculate that increased NO may be a sign of subclinical cardiotoxicity of DOX.
authors.affiliation: Department of Pediatric Oncology, Gaziantep University, Faculty of Medicine, Gaziantep, Turkey. gulerme@mynet.com
authors.forename: Elif
authors.initials: E
authors.lastname: Guler
authors.forename: Osman
authors.initials: O
authors.lastname: Baspinar
authors.forename: Mustafa
authors.initials: M
authors.lastname: Cekmen
authors.forename: Metin
authors.initials: M
authors.lastname: Kilinc
authors.forename: Ayse
authors.initials: A
authors.lastname: Balat
mesh_terms: D000293:Adolescent; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D004317:Doxorubicin / Q000009:adverse effects*; D005260:Female; D006321:Heart / Q000187:drug effects*; D006801:Humans; D008297:Male; D008482:Mediastinum / Q000528:radiation effects; D009369:Neoplasms / Q000188:drug therapy; D009569:Nitric Oxide / Q000097:blood*; D009573:Nitrites / Q000097:blood; D013318:Stroke Volume / Q000187:drug effects
chemical_list: D000903:Antibiotics, Antineoplastic; D015415:Biomarkers; D009573:Nitrites; D009569:Nitric Oxide; D004317:Doxorubicin