Contents lists available at ScienceDirect Environmental Toxicology and Pharmacology journal homepage: www.elsevier.com/locate/etap Dyslipdemia induced by chronic low dose co-exposure to lead, cadmium and manganese in rats: the role of oxidative stress Olusola Olalekan Oladipo a,b, ⁎ , Joseph Olusegun Ayo c , Suleiman Folorunsho Ambali d , Bisalla Mohammed e , Tanang Aluwong c a Biochemistry Division, National Veterinary Research Institute, P.M.B. 01, Vom, Nigeria b Department of Veterinary Pharmacology & Toxicology, Ahmadu Bello University, Zaria, Nigeria c Department of Veterinary Physiology, Ahmadu Bello University, Zaria, Nigeria d Department of Veterinary Pharmacology & Toxicology, University of Ilorin, Ilorin, Nigeria e Department of Veterinary Pathology, Ahmadu Bello University, Zaria, Nigeria ARTICLE INFO Keywords: Lead cadmium manganese zinc hypolipidaemia oxidative stress ABSTRACT Lead (Pb), cadmium (Cd) and manganese (Mn) have many potential adverse health effects in vitro and in animal models of clinical toxicity. The current study investigated the dyslipidaemic and oxidative stress effects of chronic low-dose oral exposure to Pb, Cd and Mn and the combination (Pb + Cd + Mn) in rats for 15 weeks. Chronic exposure to the metals did not significantly (P > 0.05) alter serum lipid profiles. However, the atherogenic index decreased by 32.2% in the Pb + Cd + Mn group, relative to the control. The triglyceride/ high-density lipoprotein cholesterol ratio decreased by 39.4% in the Pb + Cd + Mn group, relative to the control, and elevated by 81.8, 94.8 and 20.8%, relative to the Pb, Cd and Mn groups, respectively. While the serum concentrations of malondialdehyde significantly increased in the Mn and Pb + Cd + Mn groups, that of glutathione peroxidase-1 decreased in the Pb + Cd + Mn group, and metallothionein-1 and zinc concentrations markedly decreased in all the metal treatment groups. The results suggest that long-term exposure of rats to Pb + Cd + Mn may result in hypolipidaemia, mediated via oxidative stress and metal interactions. Individuals who are constantly exposed to environmentally relevant levels of the metals may be at risk of hypolipidaemia. 1. Introduction There is increasing evidence that environmental pollutants con- tribute to cardiovascular diseases (CVD), especially in Africa, which has a significant share of the world’s environmental pollution (Anakwue and Anakwue, 2014). Globally, lead (Pb), cadmium (Cd) and manga- nese (Mn) constitute some of the most hazardous environmental tox- icants, implicated in disease burden of animals and humans. The metals occur naturally in situations of environmental contamination and oc- cupational exposures. A pathology hazard risk ranking of contaminants identified Pb, Cd and Mn amongst five most toxic pollutants, implicated in the mining-derived mortality and morbidity in human (Bartrem et al., 2014) and animal (Orisakwe et al., 2017) pollution of Zamfara State, Nigeria. Similar situations are prevalent worldwide in the agri- cultural, smelting and welding occupations, and the mixtures can be ranked based on human and animal exposure to such combinations (Carlin et al., 2013). Dyslipidaemia is a risk factor for the development of CVDs and its complications (Aguilar-Salinas et al., 2001). Lead (Pb) mediates biolo- gical processes involved in CVD, which may be assessed with bio- markers that indicate lipid profile dysfunction and oxidative stress. Lead modulates activities of antioxidant enzymes, including glutathione peroxidases; due to up-regulation, decreased availability or by direct binding (Patrick, 2006). Positive correlation between serum Pb and cardiometabolic risk factors such as serum total cholesterol and tri- glycerides has been demonstrated in young subjects with metabolic syndrome (Poursafa et al., 2014) and cardiovascular disease in ger- iatrics (Peters et al., 2012). A vast amount of evidence confirms that exposure to cadmium (Cd) is associated with many distinct pathological changes, including http://dx.doi.org/10.1016/j.etap.2017.06.017 Received 3 January 2017; Received in revised form 1 June 2017; Accepted 20 June 2017 ⁎ Corresponding author. E-mail address: oladiposola@ymail.com (O.O. Oladipo). Abbreviations: CVD, cardiovascular diseases; NOAELS, non-observable adverse effect levels; TC, total cholesterol; TG, triglycerides; HDLc, high-density lipoprotein cholesterol; LDLc, low-density lipoprotein cholesterol; VLDLc, very low-density lipoprotein cholesterol; AI, atherogenic index; TMB, 3,3 ̍ , 5,5 ̍ tetramethlbenzidine; AOAC, Association of Official Analytical Chemists; IPCS, International Programme on Chemical Safety Environmental Toxicology and Pharmacology 53 (2017) 199–205 Available online 22 June 2017 1382-6689/ © 2017 Elsevier B.V. All rights reserved. MARK