A Model of Cadmium Uptake and Transport in Caco-2 Cells

Gerasimenko, T. N.; Senyavina, N. V.; Anisimov, N U; Tonevitskaya, S. A.

doi:10.1007/s10517-016-3373-7

Cited by 10 publications

(4 citation statements)

References 26 publications

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“…Determining intracellular Cd concentration and correlating intracellular values to extracellular concentrations have been challenging. Mathematical modeling data obtained from intestinal cell lines suggests that an external concentration of 10 μM would lead to an intracellular Cd concentration of 5000 amol/cell [ 101 ]. Cd continuously accumulates over time, at concentrations that may not significantly alter cell viability or gene expression [ 43 ].…”

Section: Insulin Resistance and Cadmium: Cellular Studiesmentioning

confidence: 99%

Emerging Links between Cadmium Exposure and Insulin Resistance: Human, Animal, and Cell Study Data

Buha

Đukić-Ćosić

Ćurčić

et al. 2020

Toxics

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Recent research has helped clarify the role of cadmium (Cd) in various pathological states. We have demonstrated Cd involvement in pancreatic cancer, as well as the bioaccumulation of Cd in the pancreas. Bioaccumulation and increased toxicity suggest that Cd may also be involved in other pancreas-mediated diseases, like diabetes. Cd falls into the category of “hyperglycemic” metals, i.e., metals that increase blood glucose levels, which could be due to increased gluconeogenesis, damage to β-cells leading to reduced insulin production, or insulin resistance at target tissue resulting in a lack of glucose uptake. This review addresses the current evidence for the role of Cd, leading to insulin resistance from human, animal, and in vitro studies. Available data have shown that Cd may affect normal insulin function through multiple pathways. There is evidence that Cd exposure results in the perturbation of the enzymes and modulatory proteins involved in insulin signal transduction at the target tissue and mutations of the insulin receptor. Cd, through well-described mechanisms of oxidative stress, inflammation, and mitochondrial damage, may also alter insulin production in β-cells. More work is necessary to elucidate the mechanisms associated with Cd-mediated insulin resistance.

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Section: Insulin Resistance and Cadmium: Cellular Studiesmentioning

confidence: 99%

Emerging Links between Cadmium Exposure and Insulin Resistance: Human, Animal, and Cell Study Data

Buha

Đukić-Ćosić

Ćurčić

et al. 2020

Toxics

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“…Therefore, research models in vitro are often used for drug transport and absorption studies. More and more cell models are used to explore the transport and absorption of flavonoids ( 6 – 8 ). Among them, Caco-2 cell model has a good correlation with in vivo research.…”

Section: Introductionmentioning

confidence: 99%

Uptake and Transport of Naringenin and Its Antioxidant Effects in Human Intestinal Epithelial Caco-2 Cells

et al. 2022

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Naringenin, a flavanone, has been reported for a wide range of pharmacological activities. However, there are few reports on the absorption, transport and antioxidant effects of naringenin. The study was to explore the uptake, transport and antioxidant effects of naringenin in vitro. Cell transmembrane resistance, lucifer yellow transmission rate, and alkaline phosphatase activity were used to evaluate the successful construction of cell model. The results showed that the absorption and transport of naringenin by Caco-2 cells were time- and concentration-dependent. Different temperatures (37 and 4°C) had a significant effect on the uptake and transport of naringenin. Verapamil, potent inhibitor of P-glycoprotein, significantly inhibit naringenin transport in Caco-2 cells. The results revealed that naringenin was a moderately absorbed biological macromolecule and can penetrate Caco-2 cells, mainly mediated by the active transport pathway involved in P-glycoprotein. At the same time, naringenin pretreatment could significantly increase the viability of H2O2-induced Caco-2 cells. Twenty four differential metabolites were identified based on cellular metabolite analysis, mainly including alanine, aspartate and glutamate metabolism, histidine metabolism, taurine and hypotaurine metabolism, pyruvate metabolism, purine metabolism, arginine biosynthesis, citrate cycle, riboflavin metabolism, and D-glutamine and D-glutamate metabolism. We concluded that the transport of naringenin by Caco-2 cells is mainly involved in active transport mediated by P-glycoprotein and naringenin may play an important role in oxidative stress-induced intestinal diseases.

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“…Therefore, the absorption of the drug in the small intestine can be evaluated by important parameters such as the Papp of the substance in the in vitro model. In recent years, the Caco-2 cell monolayer model has been widely used to study the absorption of drugs in vitro ( Gerasimenko et al, 2016 ) and is an effective in vitro model for investigating drug uptake and transport ( Yee, 1997 ; Artursson et al, 2001 ; He et al, 2003 ; Fujikawa et al, 2005 ; Jin and Di, 2008 ).…”

Section: Introductionmentioning

confidence: 99%

Investigation of the Uptake and Transport of Aspirin Eugenol Ester in the Caco-2 Cell Model

et al. 2022

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Background: Aspirin eugenol ester (AEE) is a novel medicinal compound synthesized by esterification of aspirin with eugenol using the prodrug principle. AEE has the pharmacological activities of being anti-inflammatory, antipyretic, analgesic, anti-cardiovascular diseases, and anti-oxidative stress However, its oral bioavailability is poor, and its intestinal absorption and transport characteristics are still unknown.Objective: The purpose of this study was to investigate the uptake and transport mechanisms of AEE in Caco-2 cells.Methods: The effects of time, concentration, and temperature on the transport and uptake of AEE were studied.Results: The results showed that a higher concentration of salicylic acid (SA) was detected in the supernatant of cell lysates and cell culture medium, while AEE was not detected. Therefore, the content change of AEE was expressed as the content change of its metabolite SA. In the uptake experiment, when the factors of time, concentration, and temperature were examined, the uptake of SA reached the maximum level within 30 min, and there was concentration dependence. In addition, low temperature (4°C) could significantly reduce the uptake of SA in Caco-2 cells. In the transport experiment, under the consideration of time, concentration, and temperature, the transepithelial transport of SA from AP-BL and BL-AP sides was time-dependent. The amount of SA transported in Caco-2 cells increased with the increase of concentration, but the transmembrane transport rate had no correlation with the concentration. This phenomenon may be due to the saturation phenomenon of high concentration. The efflux ratio (ER) was less than 1, which indicated that their intestinal transport mechanism was passive transport. Moreover, the temperature had a significant effect on the transport of AEE.Conclusion: In summary, intestinal absorption of AEE through Caco-2 cell monolayers was related to passive transport. The uptake and transport of AEE were concentration-dependent, and temperature significantly affected their uptake and transport. The absorption and transport characteristics of AEE may contribute to the exploration of mechanisms of absorption and transport of chemosynthetic drugs in vitro.

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A Model of Cadmium Uptake and Transport in Caco-2 Cells

Cited by 10 publications

References 26 publications

Emerging Links between Cadmium Exposure and Insulin Resistance: Human, Animal, and Cell Study Data

Emerging Links between Cadmium Exposure and Insulin Resistance: Human, Animal, and Cell Study Data

Uptake and Transport of Naringenin and Its Antioxidant Effects in Human Intestinal Epithelial Caco-2 Cells

Investigation of the Uptake and Transport of Aspirin Eugenol Ester in the Caco-2 Cell Model

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