title: Slow infusion rate of doxorubicin induces higher pro-inflammatory cytokine production.
abstract: Different infusion rates of doxorubicin (DOX) have been used for treating human malignancies. Organ toxicity after DOX infusion is a major issue in treatment disruption. However, whether different DOX infusion rates induce different toxicity is still unknown. In this study, we examined the toxicity effects of different DOX infusion rates in the early phase of organ toxicity. Thirty-six rats were randomly divided into 5-, 15-, and 30-min infusion rate groups. A single dose of DOX (8.3 mg/kg, I.V.) was administered at different infusion rates. Blood samples were collected from the femoral artery at 1, 3, 6, 9, 12, 18, 24, 36, and 48 h after DOX administration. The blood cell count and blood biochemistry were analyzed. The liver, kidney, and heart were removed for pathological examinations after the rats were sacrificed. Our findings show that the 30-min group had higher injury markers in the liver (glutamic oxaloacetic transaminase and glutamic pyruvic transaminase), kidneys (blood urea nitrogen and creatinine), and heart (creatine phosphokinase-MB and lactate dehydrogenase), and had higher tumor necrosis factor-alpha and interleukin 6 levels than did the other groups. The 30-min group also had more severe damage according to the pathological examinations. In conclusion, slower infusion of DOX induced a higher inflammatory response and greater organ damage.
authors: Institute of Medical Sciences, Tzu Chi University, Hualien 97004, Taiwan, ROC; Department of Nursing, Hsin Sheng College of Medical Care and Management, Taoyuan 32544, Taiwan, ROC.
authors: Chin-Chieh
authors: CC
authors: Tien
authors: Institute of Medical Sciences, Tzu Chi University, Hualien 97004, Taiwan, ROC; Department of Nursing, National Taichung University of Science and Technology, Taichung 40343, Taiwan, ROC.
authors: Yi-Chi
authors: YC
authors: Peng
authors: Intensive Care Unit, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan, ROC; School of Medicine, Tzu Chi University, Hualien 97004, Taiwan, ROC.
authors: Fwu-Lin
authors: FL
authors: Yang
authors: Department of Nursing, Tzu Chi University, Hualien 97004, Taiwan, ROC.
authors: Yi-Maun
authors: YM
authors: Subeq
authors: Institute of Medical Sciences, Tzu Chi University, Hualien 97004, Taiwan, ROC. Electronic address: fish@mail.tcu.edu.tw.
authors: Ru-Ping
authors: RP
authors: Lee
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000633:toxicity*; D015415:Biomarkers / Q000097:blood; D066126:Cardiotoxicity; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000209:etiology / Q000473:pathology; D016207:Cytokines / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage* / Q000633:toxicity*; D006321:Heart / Q000187:drug effects; D006331:Heart Diseases / Q000097:blood / Q000139:chemically induced / Q000473:pathology; D007249:Inflammation / Q000097:blood / Q000139:chemically induced*; D018836:Inflammation Mediators / Q000097:blood*; D007262:Infusions, Intravenous; D015850:Interleukin-6 / Q000097:blood; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011921:Rats, Inbred WKY; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000903:Antibiotics, Antineoplastic; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D004317:Doxorubicin
keywords: Acute inflammation; Cytokine; Doxorubicin; Infusion rate