Increased Hepatic and Decreased Urinary Metallothionein in Rats after Cessation of Oral Cadmium Exposure

Abstract

Abstract:We investigated the role of metallothionein (MT) in tissues after cessation of cadmium (Cd) exposure. Wistar rats of both genders were given CdCl 2 in drinking water at daily doses of 0, 2.5, 5.0 or 10.0 mg Cd ⁄ kg body-weight for 12 weeks. Half of the animals were then killed; the others were given Cd-free water for the following 16 weeks, i.e. until 28 weeks after start of the experiment (28-week rats). We observed dose-dependent increases in the levels of MT in the tissues of rats 12 weeks after beginning the experiment (12-week rats). After the exposure ceased, levels of MT in the 28-week rats changed in three ways: an increase in the liver, persistence in the kidney cortex and a decrease in the medulla, relative to those levels in their 12-week counterparts. Biomarkers of kidney dysfunction were determined to be urinary MT (UMT) and urinary N-acetyl-b-D-glucosaminidase (UNAG). After 12 weeks, we observed dose-related statistically significant increases in UMT and UNAG in all of the Cd-exposed groups. A statistically significant decrease for UNAG between the 12-and 28-week rats occurred among males at the lowest Cd dose and for UMT in all of the Cd-exposed groups. The unchanged tissue levels of MT in the kidney cortex suggest that decreased UMT is a sign either of (i) decreased transport of Cd-MT from the liver via blood plasma to the renal tubules or (ii) increased tubular reabsorption and recovery of renal tubular function.Occupational or environmental exposure to cadmium (Cd) can give rise to adverse health effects, particularly kidney damage, as a result of Cd accumulation in the kidneys [1][2][3]. Exposure through inhalation or food intake can lead to acute or chronic effects in humans. There is an important ongoing discussion in the scientific literature regarding the possible reversibility of mild and early forms of Cd-induced renal dysfunction. Human evidence, however, remains inconsistent: some authors [4][5][6] have observed that less severe renal tubular damage is reversible; others [7][8][9] have reported that, according to their experience, progression is the rule. In addition, there is only limited data available from animal experiments involving long-term oral exposure [10,11].Metallothioneins (MTs) have attracted much attention in studies of Cd toxicity since their isolation from the equine renal cortex more than 50 years ago (reviewed by Nordberg [12]). MTs comprise a family of low molecular mass (6-7 kDa) stress proteins incorporating a high content of cysteine and divalent metals. They are important participants in the homeostasis of essential trace elements (e.g. zinc, copper) and function as scavengers of free radicals. Some of the present authors [1,13] were among the first to describe the role of MTs in relation to the toxicology of Cd (reviewed by Nordberg [12]). MTs are important agents for the absorption, transport, and excretion of Cd [1,[14][15][16][17]. Studies of Cd-exposed MT knockout mice [18,19] and in a human population [20] have further underlined the significance ...

Renal Function after Reduction in Cadmium Exposure: An 8-Year Follow-up of Residents in Cadmium-Polluted Areas

“…Because of NAG’s direct relevance to the integrity of proximal tubular cells, the release of NAG into the urine is an early sign of tubular membrane damage (Bernard et al 1995; Jin et al 1999). In addition, our recent animal study (Liang et al 2010) confirmed increased hepatic and decreased urinary metallothioneins (a family of 6- to 7-kDa stress proteins incorporating a high content of cysteine and divalent metals) after cessation of oral Cd exposure, suggesting that urinary metallothionein could be another informative marker to evaluate recovery of Cd-mediated renal tubular dysfunction after a reduction in exposure.…”

Influence of cadmium ions on the antioxidant status and lipid peroxidation in mouse liver: protective effects of zinc and selenite ions

“…It has been shown that Cd ean target a number of tissues in eukaryotic organisms and induce oxidative damage by disturbing the prooxidant-antioxidant balance [2]. Exposure of an organism to Cd initiates the cellular defense mechanism by up-regulating the synthesis of metal-hinding proteins known as metallothioneins (MTs) [4]. Exposure of an organism to Cd initiates the cellular defense mechanism by up-regulating the synthesis of metal-hinding proteins known as metallothioneins (MTs) [4].…”

An assessment of sensitivity biomarkers for urinary cadmium burden

“…Long-term Cd exposure has been reported, and renal dysfunction has already been proven [45,46]. Uβ 2 -MG and UNAG are in use as biomarkers for clinical diagnosis [15,21] and animal experiments [47,48]. In the later stages of Cd-induced renal injury, the tubular epithelial cells may shrink, fall off, and even disappear, and the tissue source of UNAG is lost [49].…”