Caffeic acid phenethyl ester as a protective agent against doxorubicin nephrotoxicity in rats $ Murat Yagmurca a , Hasan Erdogan b , Mustafa Iraz c , Ahmet Songur d , Muharrem Ucar e , Ersin Fadillioglu f, * a Department of Histology and Embryology, Faculty of Medicine, Afyon Kocatepe University, Afyon, Turkey b Department of Physiology, Faculty of Medicine, Gaziosmanpasa University, Tokat, Turkey c Department of Pharmacology, Faculty of Medicine, Inonu University, Malatya, Turkey d Department of Anatomy, Faculty of Medicine, Afyon Kocatepe University, Afyon, Turkey e Department of Histology and Embryology, Faculty of Medicine, Inonu University, Malatya, Turkey f Department of Physiology, Faculty of Medicine, Inonu University, Malatya, Turkey Received 9 December 2003; received in revised form 15 March 2004; accepted 29 March 2004 Abstract Background: Nephrotoxicity is one of the important side effects of antracycline antibiotics. The aim of this study was to investigate the effects of caffeic acid phenethyl ester (CAPE), an antioxidant agent, against nephrotoxicity induced by doxorubicin (DXR). Methods: The rats were divided into control, CAPE alone, doxorubicin (20 mg/kg, i.p.) and doxorubicin plus CAPE (10 Amol/kg/day, i.p.) groups. At the end of the 10th day, kidney tissues were removed for light microscopy and analysis. The levels of tissues protein carbonyl content (PC), malondialdehyde (MDA) and nitric oxide (NO) as well as the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and myeloperoxidase (MPO) were determined. Plasma oxidants and antioxidants were also measured. Results: The activities of CAT and GSH-Px were decreased as well as myeloperoxidase, NO, MDA and PC were increased in renal tissue of doxorubicin group compared with the other groups. Plasma GSH-Px activity was higher in doxorubicin plus CAPE group than the others and plasma MDA level was higher in doxorubicin group than the other groups. There were glomerular vacuolization, tubular desquamation, loss of brush border, and adhesion to Bowman’s in the light microscopy in the kidneys of doxorubicin group. The tubules and brush border were almost normal and some of the glomerulus was filled with fine vacuoles in CAPE treated rats. Conclusion: Doxorubicin caused renal injury and CAPE treatment prevented lipid peroxidation and protein oxidation in renal tissue and partially preserved glomerulus and tubules. D 2004 Elsevier B.V. All rights reserved. Keywords: Doxorubicin; Nephrotoxicity; CAPE; Antioxidant enzymes; Nitric oxide; Myeloperoxidase 0009-8981/$ - see front matter D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.cccn.2004.03.035 Abbreviations: CAPE, caffeic acid phenethyl ester; CAT, catalase; Cu, copper; DXR, doxorubicin; GSH-Px, Glutathione peroxidase; H&E, hematoxylin and eosin; H 2 O 2 , hydrogen peroxide; iNOS, inducible nitric oxide synthase; k, rate constant; MDA, malondialdehyde; Mn, manganese; MPO, myeloperoxidase; NBT, nitroblue-tetrazolium; NO, nitric oxide; NO 2 À , nitrite; NO 3 À , nitrate; NOS, nitric oxide synthase; PAS, periodic acid-schiff; SOD, superoxide dismutase; TBA, thiobarbituric acid; XO, Xanthine oxidase; Zn, zinc. $ This study was partly presented in ‘‘EUROMEDLAB Barcelona 2003’’ Congress, Barcelona, Spain, 2003. * Corresponding author. Tip Fakultesi (Dekanlik Binasi), Inonu Universitesi, Fizyoloji Anabilim Dali, TR-44069, Malatya, Turkey. Tel.: +90-422-3410660/90-422-3411413; fax: +90-422-3410036. E-mail address: efadillioglu@yahoo.com (E. Fadillioglu). www.elsevier.com/locate/clinchim Clinica Chimica Acta 348 (2004) 27 – 34