In vitro effects of cadmium on two different animal cell models

Olabarrieta, I.; L’Azou, B; Yuric, S; Cambar, J.; Cajaraville, M.P.

doi:10.1016/s0887-2333(01)00056-x

Cited by 122 publications

(65 citation statements)

References 29 publications

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“…Pointedly, the concentrations of Cd used by these studies to induce p38 activity acutely were 4-to 20-fold greater than we used in our work, although the length of incubation was less [1-3, 10, 11, 17]. However, it should be noted that LLC-PK cells have been previously shown to be more sensitive than other cells to Cd [31,43]. Lower cytotoxic doses (!80 ÌM) were reported to also activate JNK and ERK, but not p38 [2].…”

Section: Discussionmentioning

confidence: 72%

Delayed Apoptosis Post-Cadmium Injury in Renal Proximal Tubule Epithelial Cells

Stinson

Darmon²,

Dagnino³

et al. 2002

Am J Nephrol

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Background: Accumulation of the widespread environmental toxin cadmium (Cd) in the kidney results initially in proximal tubule dysfunction. Exposure to Cd has been previously shown to induce apoptosis in LLC-PK (Lily Laboratory Culture, Porcine Kidney) cells, which are a model of proximal tubule epithelium. Hypothesis: We postulated that modulation of the components of the apoptotic pathway triggered by Cd is amenable to therapeutic intervention. Methods: We subjected confluent LLC-PK cells grown on two-compartment filters and on plastic to Cd (1–50 µM). Apoptosis and changes in components of the apoptotic pathway were measured by immunocytochemical and immunoblot analysis during the period of exposure and following Cd withdrawal. Results: Insignificant apoptosis was seen during exposure to Cd and immediately after removal of this metal. Two waves of apoptosis were noted 6 and 48 h after the Cd was removed from the apical compartment. The apoptosis 48 h post-Cd exposure was accompanied by a decrease in cellular ATP levels and transepithelial resistance and preceded by an increase in p38 phosphorylation. Inhibition of p38 mitogen-activated protein kinase activity decreased the delayed apoptotic peak, without affecting the rate of recovery of the integrity of the renal epithelium. IGF-1 neither altered the delayed apoptosis nor facilitated the rate of recovery of the integrity of the renal epithelium. Conclusion: We demonstrate that following exposure to Cd, renal epithelial cells undergo significant apoptosis, which appears to involve p38 and is not amenable to IGF therapy.

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Section: Discussionmentioning

confidence: 72%

Delayed Apoptosis Post-Cadmium Injury in Renal Proximal Tubule Epithelial Cells

Stinson

Darmon²,

Dagnino³

et al. 2002

Am J Nephrol

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“…Various freshly isolated or cultured cell types from adult mussels have been used in ecotoxicological studies, including digestive gland cells (Lowe and Pipe 1994;Birmelin and Pipe 1999;Le Pennec and Le Pennec 2001) and haemocytes (Cajaraville et al 1996;Venier et al 1997;Olabarrieta et al 2001;Gómez-Mendikute et al 2002;Gómez-Mendikute and Cajaraville 2003). In a similar way, mussel gill cells are attractive models in ecotoxicological studies, since gills are the first target and uptake site for many toxicants in the aquatic environment and, thus, gill cells are often affected by exposure to pollutants (Sunila 1986;Bigas et al 2001).…”

Section: Discussionmentioning

confidence: 99%

Characterization of mussel gill cells in vivo and in vitro

et al. 2005

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Mussel gill cells are attractive models in ecotoxicological studies because gills are the first uptake site for many toxicants in the aquatic environment; gill cells are thus often affected by exposure to pollutants. Our aim was to characterize mussel gill cells in vivo and in vitro by using morphological, histochemical and functional end-points. In paraffin sections stained with haematoxylin-eosin, three zones were distinguished in the long central gill filaments: frontal, intermediate and abfrontal. Various types of ciliated cells were present in the frontal zone, and both ciliated and non-ciliated cells were found in the abfrontal zone. The intermediate zone was comprised of flattened endothelial cells. Lipofuscin granules occurred in the three zones in variable amounts, depending on the specimen. Haemocytes were found in the haemolymph sinus of gill filaments. Mucocytes were identified in both frontal and abfrontal zones by means of periodic acid Schiff-alcian blue (PAS-AB) staining. In cryostat sections, succinate dehydrogenase (SDH) activity was mainly found in ciliated cells, whereas neutral lipids and acid-phosphatase-reactive lysosomes were present in all portions of the gill filament, mostly being related to lipofuscin granules. In mussels exposed to 5'-bromo-2'-deoxyuridine in vivo, proliferating cells were scattered throughout the gill filament. Gill cells (typically 2x10(7) cells/ml per mussel; 95% viability) were isolated by dissociation with dispase. Gill cell suspensions were heterogeneous: 58% were ciliated epithelial cells (positive for SDH), 42% were non-ciliated cells (including epithelial cells and haemocytes), 2.3% were mucocytes (positive for PAS-AB) and 4.25% were haemocytes (able to phagocytose neutral red-stained zymosan). Gill cell cultures were maintained up to 18 days without changing the culture medium, viability decreasing below 50% at day 18. Primary cultures of mussel gill cells might therefore be useful models for the in vitro assessment of xenobiotic impacts on coastal and estuarine ecosystems.

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“…For liver cells, LC 50 s of 500 lM and 70 lM were obtained following a 3-h exposure in the human HepG2 cell line and in Reuber H-35 rat hepatoma cells, respectively (Yang et al 2004b;Yang et al 1995). In contrast, renal LLC-PK1 cells were found to be much more resistant since an LC 50 around 50 mM was estimated (Olabarrieta et al 2001). Although the culture media differ, all these studies have been performed using serum-free media.…”

Section: Constitutive and Acquired Resistance To CD Vary With The Difmentioning

confidence: 99%

Resistance to cadmium as a function of Caco-2 cell differentiation: role of reactive oxygen species in cadmium- but not zinc-induced adaptation mechanisms

2009

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Cadmium (Cd) is a highly toxic metal that enters the food chain. Following oral ingestion, the intestinal epithelium is the first biological barrier crossed by Cd and is also an important target tissue. In the present study, the human intestinal Caco-2 cell line was used to evaluate the impact of a low level of exposure on both undifferentiated and differentiated intestinal cells. As revealed by the LC(50) values estimated with the 3-[4,5-dimethyl-2-thiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, mature Caco-2 cells were more resistant to Cd. However, following a 24-h exposure to non-cytotoxic levels of Cd (10 microM) or zinc (Zn, 100 microM), threefold increases were obtained in the LC(50) values of 7-day-old cells, whereas increased resistance in 21-day-old cells was observed exclusively with Zn. Induction of MT-IIa and HSP70 mRNAs was higher in undifferentiated cells and an increase in cellular glutathione (GSH) content was observed exclusively in these cell cultures. However, the results obtained with cycloheximide used for inhibiting protein synthesis and with L-buthionine sulfoximine (BSO), which inhibits GSH synthesis, revealed that protein synthesis is not a prerequisite to the development of resistance. The presence of 100 mM 3-amino-1,2,4-triazole (3AT), a catalase inhibitor, prevented Cd-induced but not Zn-induced resistance, as well as sensitized cells to Cd toxicity. These results show for the first time differences in constitutive and acquired resistance to Cd as a function of enterocytic differentiation status and suggest the involvement of different mechanisms for Cd- and Zn-induced adaptation in the intestinal cells. Redox signals may trigger Cd-induced adaptation mechanisms but pro-oxidant conditions would eliminate proliferative intestinal cells capability to develop resistance. This would be critical for Cd- but not Zn-induced mechanisms of resistance since Cd but not Zn may cause oxidative stress.

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In vitro effects of cadmium on two different animal cell models

Cited by 122 publications

References 29 publications

Delayed Apoptosis Post-Cadmium Injury in Renal Proximal Tubule Epithelial Cells

Delayed Apoptosis Post-Cadmium Injury in Renal Proximal Tubule Epithelial Cells

Characterization of mussel gill cells in vivo and in vitro

Resistance to cadmium as a function of Caco-2 cell differentiation: role of reactive oxygen species in cadmium- but not zinc-induced adaptation mechanisms

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