Long-Term Oral Intake of Low-Dose Cadmium Exacerbates Age-Related Impairment of Renal Functional Reserve in Rats

Uriu, Kohei; Kaizu, Kazo; Qie, Yue Ling; Ito, Aki; Takagi, Ichiro; Suzuka, Kanako; Inada, Y; Hashimoto, Osamu; Eto, Sumiya

doi:10.1006/taap.2000.9063

Cited by 21 publications

(17 citation statements)

References 33 publications

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“…Liver, kidney, and spleen weights per BW with Cd administration were a little higher than those without Cd administration but EFP weights per BW showed the opposite trend. Such changes in organ and tissue weights per BW with Cd administration may be caused by organ sclerosis due to Cd poisoning (28,29). As the effect of grape intake was shown only in the liver, liver weight per BW was increased largely when both Cd and grapes were administered to the SD rats.…”

Section: Discussionmentioning

confidence: 99%

Effects of Different Grape Formulations on Antioxidative Capacity, Lipid Peroxidation and Oxidative DNA Damage in Aged Rats

Rho

Kim

2006

J Nutr Sci Vitaminol

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SummaryIn this study, the freeze-dried powders from whole grapes, pomace and juice of Campbell Early (Vitis labruscana Bailey) were prepared to determine the amount of total flavonoids, vitamins A, C, and E, and dietary fiber. Effects of whole grape, pomace, or juice intakes on their antioxidative capacity and DNA damage were investigated in Sprague-Dawley male rats. A total of 120 rats at 13 mo old and weighing 549Ϯ4 g were blocked into 8 groups according to body weight and raised for 3, 5, or 7 mo with diets containing 2% (w/ w) dry powder of three different parts of grapes and 0.02% (w/w) CdCl2. The contents of flavonoids, antioxidant vitamins A and E, and dietary fiber in freeze-dried powder were the highest in grape pomace, but the vitamin C contents were similar among the three powders. In all the 16, 18, and 20-mo-old animals, plasma and liver thiobarbituric acid reactive substances levels of grape-ingesting groups were lower than those of the controls and that of the grape pomace group was the lowest among the groups. Cd administration increased plasma and liver thiobarbituric acid reactive substances levels remarkably; however, Cdϩgrape groups were lower than the Cd-control group. Red blood cell superoxide dismutase activity of 18-and 20-mo-old rats was higher than that of 16-mo-olds, showing an age-related increase; however, red blood cell catalase and glutathione peroxidase activities decreased with age. Grape diets promoted superoxide dismutase, catalase, glutathione peroxidase activities, and the grape pomace increased the activities most significantly among three different parts of the grape. Cd decreased superoxide dismutase, catalase, glutathione peroxidase activities; however Cdϩgrape groups showed similar activities to the non-Cd control group. Liver superoxide dismutase activity was decreased with age but catalase activity of 18-mo-old rats was higher than those of 16-and 20-mo-old groups, and glutathione peroxidase activities of 16-and 18-mo-old groups were similar but that of 20-mo-old groups decreased markedly. Grape intake increased these three antioxidative enzyme activities while Cd administration decreased catalase and glutathione peroxidase activities except superoxide dismutase activity. The concentration in the kidney of 8-hydroxy-2¢-deoxyguanosine in the 18-and 20-mo-old rats was higher than that in the 16-mo-old groups, and grape intake showed a protecting effect on DNA from age-related or Cd-induced oxidative damage. In conclusion, grape intakes, especially grape pomace with the highest content of flavonoids, ␤-carotene, tocopherols and dietary fiber among the three parts, showed the prominent antioxidative capacity of inhibiting age-related or Cd-induced increase of lipid peroxidation and DNA damage effectively, promoting liver and red blood cell antioxidant enzyme activities.

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Section: Discussionmentioning

confidence: 99%

Effects of Different Grape Formulations on Antioxidative Capacity, Lipid Peroxidation and Oxidative DNA Damage in Aged Rats

Rho

Kim

2006

J Nutr Sci Vitaminol

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“…After Cd is ingested through digestive tract, it accumulates in the kidneys, leading to renal damage, and Cd intoxication gives rise to nephropathia [25,26] . Long-term low-dose Cd administration to rats increases the impairment of renal functions and the degeneration of proximal tubulus epithelial cells depending on age [27] . Cd accumulates in the kidney as a result of its preferential uptake by receptor-mediated endocytosis and metallothionein-bound Cd (Cd-MT) in the proximal tubule.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Chronic Cadmium Toxicity on Blood Pressure and Plasma Viscosity

Koçak

Yazıhan²,

Akçıl

et al. 2010

Pathophysiol Haemos Thromb

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Cadmium (Cd) is a heavy metal which affects many systems in humans and animals as a consequence of environmental and industrial pollution. The aim of this study was to investigate the effect of chronic Cd toxicity on blood pressure and plasma viscosity. Experimental group rats were given doses that contained 15 ppm CdCl₂ in drinking water for 8 weeks. The systolic blood pressure and heart rate were measured from rats’ tails and recorded by plethysmography every two weeks. Blood samples were drawn, Cd levels were determined by atomic absorption spectrophotometer and plasma viscosity values by viscometer. Blood Cd levels were found to be significantly higher in the experimental group compared to the control group (p < 0.001). The whole blood analysis was made by an analyzer. Polymorphonuclear leukocytes and monocytes increased (p < 0.01) and lymphocyte number (p < 0.05) decreased in the experimental group. Viscosity values were 2.21 ± 0.54 and 1.62 ± 0.31 centipoises in the experimental and control groups, respectively (p < 0.001). In the experimental group, changes in systolic blood pressure between weeks were significant (p < 0.001) and were found to be correlated with plasma viscosity (p < 0.001). In the experimental group, changes in heart rate between weeks were significant (p < 0.001). According to our findings, Cd toxicity may lead to an increase in blood pressure by increasing plasma viscosity.

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“…However, reports concerning the simultaneous assessment of the structure and function of this organ and Cd accumulation are rare. Moreover, there are some discrepancies regarding levels of exposure and the kidney Cd concentrations at which kidneys are injured as well as regarding the severity of damage (Aughey et al 1984;Uriu et al 2000). There is still too little knowledge on kidney status in conditions of low-level long-term exposure.…”

Section: Introductionmentioning

confidence: 94%

Changes in the structure and function of the kidney of rats chronically exposed to cadmium. I. Biochemical and histopathological studies

et al. 2003

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The aim of this study was to assess the effects of chronic exposure to cadmium (Cd) on the structure and function of kidneys, as well as to establish the body burden of Cd at which the changes occur. For this purpose we have created an experimental model using rats intoxicated with Cd administered in drinking water at the concentration of 5 or 50 mg Cd/l for 6, 12 and 24 weeks. The degree of kidney damage was evaluated biochemically and histopathologically. Sensitive biomarkers of Cd-induced proximal tubular injury such as urinary total N-acetyl-beta- d-glucosaminidase (NAG-T) and its isoenzyme B (NAG-B), and alkaline phosphatase (ALP) were used. Cd content in the kidney increased with the level and duration of exposure leading to dose- and time-dependent structural and functional renal failure. In rats exposed to 5 mg Cd/l, first symptoms of injury of the main tubules of long and short nephrons (structural damage to epithelial cells, increased urinary activities of NAG-T and NAG-B) were noted after 12 weeks of the experiment. The damage occurred at a low kidney Cd concentration amounting to 4.08+/-0.33 micro g/g wet weight (mean +/-SE) and a urinary concentration of 4.31+/-0.28 micro g/g creatinine. On exposure to 50 mg Cd/l, damage to the main tubules (blurred structure of tubular epithelium, atrophy of brush border, partial fragmentation of cells with release of nuclei into tubular lumen as well as increased urinary activities of NAG-T, NAG-B and ALP) was already evident after 6 weeks with the kidney Cd concentration of 24.09+/-1.72 micro g/g wet weight. In rats exposed to 50 mg Cd/l, a lack of regular contour of glomeruli was noted after 12 weeks, whereas after 24 weeks thickening of capillary vessels and widening of filtering space were evident. After 24 weeks of exposure to Cd, increased urea concentration in the serum with simultaneous decrease in its level in the urine, indicating decreased clearance of urea, and increased excretion of total protein were observed, but endogenous creatinine clearance remained unaffected. At the lower exposure, symptoms of structural, but not functional, damage to the glomeruli were also evident after 24 weeks of the experiment. Our results provide evidence that chronic exposure to Cd dose-dependently damages (structurally and functionally) the whole kidney. The injury affects the main resorptive part (proximal convoluted tubules and straight tubules) and the filtering part (glomeruli) of the nephron. But the target site for Cd action is the main tubule. We hypothesize that the threshold for Cd effects on the kidney is less than 4.08+/-0.33 micro g/g wet kidney weight and greater than 2.40+/-0.15 micro g/g (at this Cd concentration no symptoms of kidney damage were noted), and it may be close to the latter value. A very important finding of this study is that Cd acts on the whole kidney, especially on the main tubules, even at relatively low accumulation in this organ. It confirms the hypothesis that humans environmentally exposed to Cd, especially smokers, are at risk of t...

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Long-Term Oral Intake of Low-Dose Cadmium Exacerbates Age-Related Impairment of Renal Functional Reserve in Rats

Cited by 21 publications

References 33 publications

Effects of Different Grape Formulations on Antioxidative Capacity, Lipid Peroxidation and Oxidative DNA Damage in Aged Rats

Effects of Different Grape Formulations on Antioxidative Capacity, Lipid Peroxidation and Oxidative DNA Damage in Aged Rats

The Effect of Chronic Cadmium Toxicity on Blood Pressure and Plasma Viscosity

Changes in the structure and function of the kidney of rats chronically exposed to cadmium. I. Biochemical and histopathological studies

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