Toxicity of copper intake: lipid proﬁle, oxidative stress and susceptibility to renal dysfunction
Cristiano M. Galhardi a, Yeda S. Diniz b, Luciane A. Faine b, Hosana G. Rodrigues a, Regina C.M. Burneiko b, Bartolome O. Ribas c, Ethel L.B. Novelli a,*
Department of Chemistry andBiochemistry, Institute of Biological Sciences, University Estadual Paulista-UNESP, Botucatu, Sao Paulo, Brazil ˜ Post Graduation Course, Department of Clinical and Cardiology, Faculty of Medicine, University Estadual Paulista, Botucatu, Sao Paulo, Brazil ˜ c Department of Toxicology, Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo, Madrid, Spain Received 9 January 2004; accepted29 July 2004
Abstract The present study was carried out to investigate the eﬀects of copper (Cu) intake on lipid proﬁle, oxidative stress and tissue damage in normal and in diabetic condition. Since diabetes mellitus is a situation of high-risk susceptibility to toxic compounds, we examined potential early markers of Cu excess in diabetic animals. Male Wistar rats, at 60-days-old were dividedinto six groups of eight rats each. The control(C) received saline from gastric tube, the no-diabetic(Cu-10), treated with 10 mg/kg of Cu(Cu++– CuSO4, gastric tube), no-diabetic with Cu-60 mg/kg(Cu-60), diabetic(D), diabetic low-Cu(DCu-10) and diabetic high-Cu(DCu60). Diabetes was induced by an ip injection of streptozotocin (60 mg/kg). After 30 days of treatments, no changes were observed in serumlactate dehydrogenase, alanine transaminase and alkaline phosphatase, indicating no adverse eﬀects on cardiac and hepatic tissues. D-rats had glucose intolerance and dyslipidemic proﬁle. Cholesterol and LDL-cholesterol were higher in Cu-60 and DCu-60 than in C, Cu-10 and D and DCu-10 groups respectively. Cu-60 rats had higher lipid hydroperoxide (HP) and lower superoxide dismutase (SOD) andglutathione peroxidase (GSH-Px) serum activities than C and Cu-10 rats. LH was increased and GSH-Px was decreased, while no alterations were observed in SOD and catalase in serum of DCu-60 animals. DCu-60 rats had increased urinary glucose, creatinine and albumin. In conclusion, Cu intake at high concentration induced adverse eﬀects on lipid proﬁle, associated with oxidative stress and diminishedactivities of antioxidant enzymes. Diabetic animals were more susceptible to copper toxicity. High Cu intake induced dyslipidemic proﬁle, oxidative stress and kidney dysfunction in diabetic condition. Copper renal toxicity was associated with oxidative stress and reduction at least, one of the antioxidant enzymes. Ó 2004 Elsevier Ltd. All rights reserved.
Keywords: Copper; Lipid proﬁle; Oxidativestress; Kidney; Diabetes mellitus
Abbreviations: ALP, falkaline phosphatase; ALT, alanine transaminase; BHT, butylated hydroxytoluene; Ce, ceruloplasmin; EDTA, ethylenediamine tetraacetic acid; GSH-Px, glutathione peroxidase; HDL, high density lipoprotein; H2O2, hydrogen peroxide; LDH, lactate dehydrogenase; LDL, low density lipoprotein; LH, lipid hydroperoxide; NADP, nicotinamideadenine dinucleotide phosphate oxidized form; NBT, nitro blue tetrazolium; ROS, reactive oxygen species; SOD, superoxide dismutase; TG, triacylglycerol; VLDL, very low density lipoprotein * Corresponding author. Tel.: +55 14 38116255/68026255; fax: +55 14 38153744/68213744. E-mail address: firstname.lastname@example.org (E.L.B. Novelli). 0278-6915/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.doi:10.1016/j.fct.2004.07.020
Copper (Cu) products act as components of large systems, such as building, magnet, motor vehicle and telecom wire, copper tube, sheet and strip and many alloy products (Spatari et al., 2002). Cu in tailings and smelter slag is a potential environmental hazard (Gordon, 2002), and high Cu in drinking water transported through corroded Cu tube have been frequently...