Pathological Study on Beagles after Long-term Oral Administration of Cadmium

Hamada, Tetsuo; Nakano, Shigeo; Iwai, Shigetoshi; Tanimoto, Akihide; Ariyoshi, Kayoko; Koide, Osamu

doi:10.1177/019262339101900208

Cited by 54 publications

(40 citation statements)

References 15 publications

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“…[1][2][3] It has been well recognized that Cd-related cytotoxicity is closely associated with oxidative stress, which is induced by the generation of ROS and the disturbance of anti-oxidative enzymes, such as catalase and GSH-Px 19) ; however, the effect of Cd exposure on the expression of EC-SOD and other SODs has not been elucidated. In this study, we demonstrate for the first time that EC-SOD was decreased by CdCl 2 exposure through intracellular ROS accumulation and the p38-MAPK pathway in COS7 cells.…”

Section: Discussionmentioning

confidence: 99%

Extracellular-Superoxide Dismutase Expression in COS7 Cells Exposed to Cadmium Chloride

Obara

Kamiya

Izumi

et al. 2011

Biological & Pharmaceutical Bulletin

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Cadmium (Cd), an industrial and environmental pollutant, preferentially accumulates in the kidney, a major target for Cd-related toxicity. It has been reported that Cd exposure produces reactive oxygen species (ROS) and induces cytotoxicity. Extracellular-superoxide dismutase (EC-SOD) is an antioxidant enzyme that protects the cells from damaging effects of ROS; however, the effect of Cd on the expression of EC-SOD in COS7 cells remains unclear. In this study, exposure to cadmium chloride (CdCl 2 ) enhanced intracellular ROS generation and induced COS7 cell death. Moreover, exposure to Cd decreased the expression of EC-SOD at mRNA and protein levels, but not of other SOD isozymes, copper-and zinc-containing SOD and manganese-containing SOD. The reduction of EC-SOD and cell viability was partially attenuated by pretreatment with an antioxidant, Nacetylcysteine. Further, we determined the involvement of p38-mitogen-activated protein kinase (p38-MAPK) in the reduction of EC-SOD. From these observations, p38-MAPK signaling cascades activated by ROS play a pivotal role in the reduction of EC-SOD, and it is concluded that the reduction of EC-SOD leads to a decrease in the resistance to oxidative stress of Cd-exposed COS7 cells.

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Section: Discussionmentioning

confidence: 99%

Extracellular-Superoxide Dismutase Expression in COS7 Cells Exposed to Cadmium Chloride

Obara

Kamiya

Izumi

et al. 2011

Biological & Pharmaceutical Bulletin

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“…However, it has also been apparent that early manifestations of cadmiuminduced proximal tubule dysfunction occur well before the onset of necrosis. In the 1990s, several investigators (Hamada et al, 1991;Tanimoto et al, 1993Tanimoto et al, , 1999Yan et al, 1997) published results showing that the early stages of cadmium nephrotoxicity were associated with an increase in the number of apoptotic cells in the proximal tubule. In each of these studies, there was no significant evidence of necrotic injury at the time that apoptosis was observed.…”

Section: Role Of Necrosis Apoptosis and Autophagy In Cadmium Nephromentioning

confidence: 99%

Mechanisms of Cadmium-Induced Proximal Tubule Injury: New Insights with Implications for Biomonitoring and Therapeutic Interventions

Prozialeck

Edwards

2012

J Pharmacol Exp Ther

214

150

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Cadmium is an important industrial agent and environmental pollutant that is a major cause of kidney disease. With chronic exposure, cadmium accumulates in the epithelial cells of the proximal tubule, resulting in a generalized reabsorptive dysfunction characterized by polyuria and low-molecular-weight proteinuria. The traditional view has been that as cadmium accumulates in proximal tubule cells, it produces a variety of relatively nonspecific toxic effects that result in the death of renal epithelial cells through necrotic or apoptotic mechanisms. However, a growing volume of evidence suggests that rather than merely being a consequence of cell death, the early stages of cadmium-induced proximal tubule injury may involve much more specific changes in cell-cell adhesion, cellular signaling pathways, and autophagic responses that occur well before the onset of necrosis or apoptosis. In this commentary, we summarize these recent findings, and we offer our own perspectives as to how they relate to the toxic actions of cadmium in the kidney. In addition, we highlight recent findings, suggesting that it may be possible to detect the early stages of cadmium toxicity through the use of improved biomarkers. Finally, some of the therapeutic implications of these findings will be considered. Because cadmium is, in many respects, a model cumulative nephrotoxicant, these insights may have broader implications regarding the general mechanisms through which a variety of drugs and toxic chemicals damage the kidney.

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“…Some researchers insist that the major cause of IID is not Cd, but rather malnutrition, especially hypovitaminosis D (Takeuchi 1973). Many researchers have tried to reproduce histopathological features characteristic of IID in various animals by chronic Cd exposure (Furuta 1978;Hamada et al 1991;Itokawa et al 1974;Kajikawa et al 1981;Kawashima et al 1988;Ogoshi et al 1989), but few of them were successful in reproducing osteoporosis with osteomalacia characteristic to IID. In our previous report (Hiratsuka et al 1996), osteoporosis with osteomalacia, tubular nephropathy, and renal anemia were induced in ovariectomized (OX) female rats by i.v.…”

Section: Introductionmentioning

confidence: 99%

The Effects of a Vitamin D–deficient Diet on Chronic Cadmium Exposure in Rats

et al. 2010

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Itai-itai disease (IID) of humans is one of the most severe forms of chronic cadmium (Cd) intoxication. Itai-itai disease occurs mainly in postmenopausal women and is characterized by osteoporosis with osteomalacia, renal tubular disorder, and renal anemia. Some researchers insist the major cause of IID is not Cd, but rather malnutrition, especially hypovitaminosis D. We administrated a low concentration of Cd chloride intravenously to ovariectomized female rats that were fed a vitamin D-deficient diet or a normal diet for fifty weeks. The vitamin D-deficient diet decreased serum concentration of vitamin D, but it did not affect the metabolism of the kidney or bone. Cadmium treatment alone induced a decrease in serum concentration of vitamin D, as well as renal dysfunction, renal anemia, and abnormal bone metabolism. Osteoporosis with osteomalacia, tubular nephropathy, fibrous osteodystrophy, and bone marrow hyperplasia occurred following Cd treatment. In rats treated with Cd and administered a vitamin D-deficient diet, the toxic effects of Cd on kidney, bone, and hematopoiesis were enhanced in comparison to rats treated with Cd and a normal diet. The present experiment demonstrated that hypovitaminosis D did not evoke morphologic features of IID in humans but did enhance Cd-induced toxicity in the rat model of this disease.

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Pathological Study on Beagles after Long-term Oral Administration of Cadmium

Cited by 54 publications

References 15 publications

Extracellular-Superoxide Dismutase Expression in COS7 Cells Exposed to Cadmium Chloride

Extracellular-Superoxide Dismutase Expression in COS7 Cells Exposed to Cadmium Chloride

Mechanisms of Cadmium-Induced Proximal Tubule Injury: New Insights with Implications for Biomonitoring and Therapeutic Interventions

The Effects of a Vitamin D–deficient Diet on Chronic Cadmium Exposure in Rats

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