Environmental Toxicology and Pharmacology 26 (2008) 297–304 Contents lists available at ScienceDirect Environmental Toxicology and Pharmacology journal homepage: www.elsevier.com/locate/etap Reversal of ionoregulatory disruptions in occupational lead exposure by vitamin C E. Abam a , B.S. Okediran a , O.O. Odukoya b , I. Adamson a , O. Ademuyiwa a,∗ a Department of Biochemistry, University of Agriculture, Abeokuta, Nigeria b Department of Chemistry, University of Agriculture, Abeokuta, Nigeria article info Article history: Received 17 April 2008 Received in revised form 25 May 2008 Accepted 29 May 2008 Available online 10 June 2008 Keywords: Lead poisoning Calcium–magnesium homeostasis Ca 2+ -Mg 2+ -ATPase Artisans in Nigeria Ascorbic acid abstract In order to investigate the toxic effects of lead during occupational exposure to this metal and the antidotal efficacy of ascorbic acid directed against these toxic effects, various artisans in Abeokuta, Nigeria, who have been shown to be occupationally exposed to lead were supplemented daily with 500 mg ascorbic acid for 2 weeks. Ca 2+ -Mg 2+ -ATPase activity in erythrocyte membrane, as well as calcium and magnesium concentrations in plasma, erythrocytes, erythrocyte membrane and urine of the artisans were determined before and after ascorbic acid supplementation. The 2-week ascorbic acid administration resulted in the reversal of lead-induced accumulation of calcium and magnesium in the erythrocyte membranes of the artisans. Ascorbic acid also reversed lead-induced inhibition of erythrocyte membrane Ca 2+ -Mg 2+ -ATPase. Urinary excretion of calcium and magnesium was not affected by ascorbic acid. There may be some scope in introducing ascorbic acid as an intervention strategy for the prevention and therapy of lead intoxication, especially in cases where the subjects cannot be removed from the source of lead exposure. © 2008 Elsevier B.V. All rights reserved. 1. Introduction Lead is a widely recognized ubiquitous, long-lived and perva- sive environmental and industrial toxicant throughout the world (Lin-Fu, 1991; Luo and Berman, 1997; Ademuyiwa et al., 2005a,b, 2007; Spivey, 2007). The known broad spectrum of toxicological effects it induces, together with the substantial risk posed to the human population throughout the world, make lead exposure an important public health problem (Canfield et al., 2003; Ademuyiwa et al., 2005a,b, 2007; Gilbert and Weiss, 2006; Park et al., 2006; Ogunseitan and Smith, 2007; Spivey, 2007). Although lead produces a plethora of effects on numerous organ systems and biochemical activities, its toxic effects tend to fall into three major categories. The primary toxicity of lead derives from its ability to cause oxidative stress by inducing the generation of reac- tive oxygen species, reducing the antioxidant defense system of cells via depletion of glutathione, inhibiting sulfhydryl-dependent enzymes and/or increasing susceptibility of cells to oxidative attack (Hsu et al., 1998; Gurer and Ercal, 2000; Osterode and Ulberth, 2000; Onunkwor et al., 2004). The second group of effects result from its chemical similarity to calcium. This similarity allows lead access to critical cellular pathways, particularly within the mito- chondria and in second messenger systems, where it competitively antagonizes calcium’s action (Goyer, 1991; De Roos, 2003). This ∗ Corresponding author. Tel.: +234 803 3575238. E-mail address: adelad2@yahoo.com (O. Ademuyiwa). action of lead affects calcium-dependent processes which include metal transport, energy metabolism, apoptosis, ionic conduction, cell adhesion, inter- and intracellular signaling and protein matura- tion (Nolan and Shaikh, 1992; Handlogten et al., 2000). Thirdly, lead appears to affect nucleic acids by an undefined mechanism, raising concern about chromosomal abnormalities and genetic regulation (Danadevi et al., 2003; Garza et al., 2006). The current therapeutic strategy in the overall management of lead toxicity is the administration of chelating agents (Staudinger and Roth, 1998; Gurer and Ercal, 2000). The most commonly employed chelating agents in the treatment of lead poisoning are calcium disodium ethylene diamine tetraacetic acid (CaNa 2 EDTA), succimer (2,3-meso-dimercaptosuccinic acid) and d-penicillamine (Aposhian et al., 1995; Staudinger and Roth, 1998; Dawson et al., 1999; Gurer and Ercal, 2000). While these agents reduce blood lead levels and increase the urinary excretion of the metal, their safety and efficacy are less well established (Aposhian et al., 1995; Staudinger and Roth, 1998; Dawson et al., 1999; Gurer and Ercal, 2000). In addition to the many serious side effects (which in them- selves represent a risk apart from the lead toxicity), these agents are generally non-specific with regards to their affinity for metals. To varying degrees, their administration results in alterations in the metabolism of a wide range of metals, including essential elements like calcium, zinc, copper, iron and manganese (Chisolm, 1990; Goyer, 1991; Ibim et al., 1992; Aposhian et al., 1995; Staudinger and Roth, 1998; Gurer and Ercal, 2000). These ion shifts between various compartments in the cell play a key role in the toxicity associated with these conventional chelating agents. 1382-6689/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.etap.2008.05.008