Erdosteine prevents doxorubicin-induced cardiotoxicity in rats.
The clinical use of doxorubicin (Dxr) is limited by its cardiotoxic effects which are mediated by oxygen radicals. The purpose of this study was to investigate in vivo protective effects of erdosteine, an antioxidant agent because of its secondary active metabolites in vivo, against the cardiotoxicity induced by Dxr in rats. Three groups of male Sprague-Dawley rats (60 days old) were used. Group 1 was untreated group used as control; the other groups were treated with Dxr (single i.p. dosage of 20 mg kg(-1) b.wt.) or Dxr plus erdosteine (10 mg kg(-1) day(-1), orally), respectively. Erdosteine or oral saline treatment was done starting 2 days before Dxr for 12 days. The analyses were done at the 10th day of Dxr treatment. The protein carbonyl content, the activities of myeloperoxidase, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and creatine kinase (CK) as well as heart rate and blood pressures were significantly increased in Dxr group in comparison with the other groups. However, pulse pressure was decreased in Dxr group. The body and heart weights were decreased in both Dxr administered groups in comparison with control group. Disorganization of myocardial histology, picnotic nuclei, edema, and increase in collagen content around vessels were seen in the slides of Dxr group, whereas normal myocardial microscopy was preserved in Dxr plus erdosteine group. Collectively, these in vivo hemodynamic, enzymatic and morphologic studies provide an evidence for a possible prevention of cardiac toxicity in Dxr-treated patients.
Yagmurca
Murat
M
Department of Histology and Embryology, Medical Faculty of Afyon Kocatepe University, Afyon, Turkey.
Fadillioglu
Ersin
E
Erdogan
Hasan
H
Ucar
Muharrem
M
Sogut
Sadik
S
Irmak
M Kemal
MK
D000284:Administration, Oral; D000818:Animals; D001219:Aspartate Aminotransferases / Q000096:biosynthesis / Q000737:chemistry / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003402:Creatine Kinase / Q000096:biosynthesis / Q000737:chemistry / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects*; D004334:Drug Administration Schedule; D006331:Heart Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007274:Injections, Intraperitoneal; D007770:L-Lactate Dehydrogenase / Q000096:biosynthesis / Q000737:chemistry / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000737:chemistry / Q000201:enzymology; D009929:Organ Size / Q000187:drug effects; D009195:Peroxidase / Q000096:biosynthesis / Q000737:chemistry / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013864:Thioglycolates / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013876:Thiophenes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014421:Turkey
D013864:Thioglycolates; D013876:Thiophenes; C048498:erdosteine; D004317:Doxorubicin; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase; D001219:Aspartate Aminotransferases; D003402:Creatine Kinase