Cadmium-Induced Osteomalacic and Osteopetrotic Lesions in Ovariectomized Rats

Katsuta, Osamu; Hiratsuka, Hideaki; Matsumoto, Junko; Iwata, Hijiri; Toyota, Naoto; Tsuchitani, Minoru; Umemura, Takashi; Marumo, Fumiaki

doi:10.1006/taap.1994.1090

Cited by 38 publications

(29 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The outbreak of itai-itai disease in Japan in the 1940s brought public awareness of cadmium toxicity with reports of individuals suffering from renal dysfunction and osteomalacia following exposure (Tsuchiya, 1978). Extensive research has since been carried out to evaluate the effects of cadmium on the skeleton, linking exposure to increased risk of bone factures and development of osteoporosis in humans (Staessen et al, 1999;Alfvén et al, 2000;Järup & Alfvén, 2004;Jin et al, 2004) and experimental animals (Katsuta et al, 1994;Regunathan et al, 2003;Brzóska & Moniuszko-Jakoniuk, 2004;. There are two proposed mechanisms underlying cadmium influences on bone function.…”

mentioning

confidence: 97%

Cadmium Induces Apoptosis in the Human Osteoblast-like Cell Line Saos-2

Coonse

Coonts

Morrison

et al. 2007

Journal of Toxicology and Environmental Health, Part A

View full text Add to dashboard Cite

Human exposure to the heavy metal cadmium has been associated with the development of bone diseases, including osteoporosis and osteomalacia. The mechanisms by which cadmium exerts a direct effect on bone remain unclear. Bone cells go through apoptosis for proper bone remodeling; therefore, it was hypothesized that cadmium disrupts this normal balance by inducing apoptosis. Human osteoblast-like cells (Saos-2) were treated with 10-200 muM cadmium chloride (CdCl2) and evaluated by trypan blue staining and phase-contrast microscopy. Exposure to CdCl2 resulted in decreased cell viability and changes in cell morphology characteristic of apoptosis. The role of apoptosis in cadmium-induced toxicity was further evaluated using the fluorescent marker annexin V, which detects externalization of cell membrane phosphatidylserine. Nuclear changes associated with apoptosis were assessed by Hoechst staining and a DNA fragmentation assay. A significant increase in annexin V-positive cells was observed following CdCl2 treatment. Nuclear changes associated with apoptosis, including marginalization and condensing of chromatin and DNA fragmentation, were also observed following CdCl2 treatment. Cadmium-induced apoptosis in Saos-2 cells was also accompanied by an increase in caspase-3 activity. The addition of the caspase-3 inhibitor N-acetyl-Asp-Glu-Val-Asp-aldehyde (Ac-DEVD-CHO) or the known cadmium chelating agent potassium bis(2-hydroxyethy)dithiocarbamate, (K[bhedtc]), blocked caspase-3 activation induced by cadmium. Collectively, this study has identified a role for apoptosis in cadmium-induced toxicity in bone cells, and provides insight for future studies on mechanisms underlying the disruption of apoptotic signaling cascades in bone and the relationship to bone disease.

show abstract

mentioning

confidence: 97%

Cadmium Induces Apoptosis in the Human Osteoblast-like Cell Line Saos-2

Coonse

Coonts

Morrison

et al. 2007

Journal of Toxicology and Environmental Health, Part A

View full text Add to dashboard Cite

show abstract

“…From these findings, it is possible that ironcontaining pigment in the cytoplasm of ameloblasts was displaced directly with Cd. We previously reported the occurrence of iron-deficient anemia in the Cd-treated rats (11,12). Therefore, discoloration of incisors in Cd-treated rats may also be induced by indirect effect of Cd via systemic iron-deficient anemia in some degree.…”

Section: Discussionmentioning

confidence: 99%

“…We found that ovariectomy enhanced toxic effects of Cd in rats (12), and Cd treatment for 13 wk induced osteomalacic and osteopetrotic lesions together with renal tubular atrophy and interstitial fibrosis in ovariectomized female rats (11). At …”

Section: Introductionmentioning

confidence: 93%

Cadmium-Induced Dental Lesions in Ovariectomized Rats

et al. 1996

View full text Add to dashboard Cite

The effects of cadmium chloride on both incisor and molar teeth of ovariectomized female rats were studied histopathologically. The rats were injected intravenously with the compound at doses of 1.0 and 2.0 mg/kg, 5 days/wk. Six rats per group were sacrificed at 4, 8, and 13 wk.Discoloration of the incisors was observed in the rats of the 2.0-mg/kg group from 8 wk. Histopathologic examination of the incisor demonstrated decreased iron-containing pigment in ameloblasts and destruction of the enamel organ. These changes were accompanied with accumulation of cadmium and loss of iron in the teeth. Necrosis of the dental pulp occurred from the coronal end of both the incisor and molar teeth extended to the apical, deep portion of the teeth. The dental pulp of the molar teeth, which is shorter than that of the incisor, was mildly affected by cadmium intoxication. These findings suggested that intradental ischemia due to cadmium toxicity may have contributed to the development of the pulpal necrosis.

show abstract

“…Animals were weighed every 3-weeks to assess changes in the body mass. CON, OVX and OM animals were euthanized via CO 2 inhalation 12-weeks after arrival at the animal facility based on the previous studies assessing the onset of quantifiable manifestations of ovariectomy by our group (Nazarian et al, 2008a,b;Cory et al, 2009) and others (Katsuta et al, 1994;Oste et al, 2005).…”

Section: Animal Modelmentioning

confidence: 99%