Gender Differences in Zinc and Copper Excretion in Response to Co-Exposure to Low Environmental Concentrations of Cadmium and Lead

Abstract

Disruption of the homeostasis of zinc (Zn) and copper (Cu) has been associated with nephrotoxicity of cadmium (Cd). Herein, we report the results of a cross sectional analysis of urinary excretion of Zn, Cu, Cd and lead (Pb) in 392 Thais (mean age 33.6) living in an area of low-level environmental exposure to Cd and Pb, reflected by the respective median Cd and Pb excretion rates of 0.44 and 1.75 μg/g creatinine. Evidence for dysregulation of Zn and Cu homeostasis has emerged together with gender differentiated responses. In men, excretion rates for Zn and Cu were increased concomitantly, and their urinary Zn-to-Cu ratios were maintained. In women, only Cu excretion rose, causing a reduction in urinary Zn-to-Cu ratios. Only in women, urinary Zn-to-Cu ratios were associated with worse kidney function, assessed by estimated glomerular filtration rate (eGFR) (β = −7.76, p = 0.015). Only in men, a positive association was seen between eGFR and body iron stores, reflected by serum ferritin (β = 5.32, p = 0.030). Thus, co-exposure to Cd and Pb may disrupt the homeostasis of Zn and Cu more severely in women than men, while urinary Zn-to-Cu ratios and body iron stores can serve as predictors of an adverse effect of co-exposure to Cd and Pb.

Metals and Metallothionein Expression in Relation to Progression of Chronic Kidney Disease of Unknown Etiology (CKDu) in Sri Lanka

“…In the present study, intergroup comparison of individual metal data ( Figure 4 A) and testing of linear correlation ( Figure 4 B), respectively, suggests disrupted homeostasis and metal accumulation in plasma as the chronic renal disease progresses in CKDu endemic PDV area. Involvement of the kidneys in metal homeostasis is known for Ni [ 47 ], Fe [ 48 ], Zn [ 49 ], Cu [ 50 ], As, Cd, Pb [ 51 ], Hg [ 52 ], Cs Cr, U [ 53 ], and Al [ 54 ]. It involves adequate filtration and reabsorption from tubular lumen [ 55 ] so that progressive tubulointerstitial damage in CKD/CKDu [ 3 ] should be fundamental to the observed variation.…”

The Evolving Role for Zinc and Zinc Transporters in Cadmium Tolerance and Urothelial Cancer

“…In another study in mice, an increased susceptibility to lung injury after a prolonged exposure to cigarette smoke was attributable to a disturbed Zn homeostasis resulting from an insufficient Zn intake or overexpression of ZIP8 [58]. Of relevance, evidence for Cd-induced derangement of cellular homeostasis of Zn and Cu has been reported in Australian [59], Thai [60,61], and Korean [62] studies.…”