Relationship between Renal Dysfunction and Bone Metabolism Disorder in Male Rats after Long-Term Oral Quantitative Cadmium Administration.

Abstract

To investigate the importance of the cadmium (Cd) exposure condition in the evaluation of toxic effect on renal function and bone metabolism, six groups of Male Wistar rats were given Cd at respective daily doses of 2, 5, 10, 20, 30 and 60 mgCd/kg (as CdCl 2 ) via a gastric tube for 6 consecutive days a week for 60 weeks. In the groups given a low Cd dose (2, 5 and 10 mgCd/kg), relatively more Cd accumulated in the kidney without liver damage than in the liver. In the high Cd dose groups (20, 30 and 60 mgCd/kg), on the other hand, more Cd accumulated in the liver than in the kidney. The daily intake of Cd dose from the intestinal tract in each experimental group was deduced to be about 0.36%-0.54% of the cumulative dose of oral Cd administration. The daily intake of Cd into the body was estimated as 7, 22, 40, 100, 120, 260 µgCd/kg/day in the experimental groups of 2, 5, 10, 20, 30 and 60 mgCd/kg/day, respectively. Increase of plasma enzyme activity (GOT, GPT) and of urinary enzyme excretion (NAG, AAP, GST), reflecting hepatic damage and renal dysfunction, was found in the high Cd dose groups (30 and 60 mgCd/kg) from the 5th week. Non-CdMT concentration in the kidney was also significantly high in the high Cd dose groups. In the low Cd dose groups (2 and 5 mgCd/kg), although the renal Cd concentration was higher than that of the high Cd dose groups, prominent renal dysfunction and hepatic damage were not observed. Regeneration, vacuolization, and eosinophilic bodies in proximal tubular tissue were mainly observed in the groups subjected to 20, 30 and 60 mgCd/kg administration. Very slight regeneration was also observed in the renal proximal tubular tissue at the 30th week for the 5 mgCd/kg and 10 mgCd/kg groups, and at the 60th week for the 2 mgCd/kg group. Remarkable decrease of bone mineral density at the midpoint of the femur was found in the high Cd dose groups. Also, the decrease in bone mineral density was observed before or after the manifestation of the renal dysfunction, depending on the dose and the duration of Cd administration. Urinary excretion of Pyr, DPyr, and Ca increased and plasma BGP decreased in the higher Cd dose groups. Osteoid volume in the femur tissue was not increased significantly by Cd exposure. Based on these results, it was suggested that Cd exposure caused osteoporotic change. The results of the present study suggested that the toxic effect of Cd on renal function and that on bone metabolism were caused at different times and that renal Cd concentration after long-term oral Cd administration depended on the dose and the duration of Cd exposure.

Participation of metal transporters in cadmium transport from mother rat to fetus

“…We also referred to an experimental study of long-term oral Cd administration in rats (Ohta et al, 2000). Based upon these studies, we determined that an oral Cd dose of 1 mg/kg would be similar to the daily level of Cd intake in humans.…”

“…In laboratory animals, renal damage and osteoporosis are the major adverse health effects associated with exposure to low levels of Cd (Brzoska and Moniuszko-Jakoniuk, 2004;Honda et al, 2003;Ohta et al, 2000). Metallothionein (MT) is a metal-binding protein that regulates the homeostasis of biologically essential metals and is also involved in the absorption, transportation, and accumulation of heavy metals such as Cd.…”

Protective Effect of Quercetin Against Renal Toxicity Induced by Cadmium in Rats

“…Chronic intake of Cd in food or in air produces organ dysfunction as a result of cell death (3). Cd is widely used in pigments, plastic stabilizers, electroplating, alloys, nickel-Cd batteries, and welding in industry and is also present in tobacco (4,5). Natural sources of Cd are spread into the atmosphere by volcanic activity, forest fires, and wind-blown transport of soil particles.…”

Health effects of low-level cadmium intake and the role of metallothionein on cadmium transport from mother rats to fetus

“…The PVDF membrane was incubated with 0.5 % skim milk in TBS (pH 8.0) containing 0.05 % Tween 20 (Tween-TBS) and subsequently incubated overnight with rabbit anti-metal-binding protein primary antibody. The primary antibody used recognizes rat MT, and was the same antibody used in a previously reported study (Ohta et al, 2000). After washing with Tween-TBS, the membrane was incubated with an alkaline phosphatase-conjugated secondary antibody for 90 min.…”

“…Cd is present in food or water, and accumulates in human or animal tissues especially the liver and kidney. It has been reported that exposure to low levels of Cd may result in renal damage and osteoporosis, which are considered to be the major adverse health effects of Cd exposure in laboratory animals (Brzoska and Moniuszko-Jakoniuk, 2004;Honda et al, 2003;Ohta et al, 2000).…”