In vitro–in vivo extrapolation: estimation of human serum concentrations of chemicals equivalent to cytotoxic concentrations in vitro

Gülden, Michael; Seibert, Hasso

doi:10.1016/s0300-483x(03)00146-x

Cited by 86 publications

(78 citation statements)

References 20 publications

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“…When assessing the therapeutic potential of any novel sample in vitro, it is important to consider the cell as a whole and to study the molecular mechanisms underlying different modulating activities caused by the sample on individual components within the cell (Gü lden & Seibert, 2003). To determine if casein hydrolysates influence the growth and viability of Jurkat cells and Caco-2 cells, four different assays were selected, namely the MTT, LDH release, Trypan Blue, and BrdU incorporation assays.…”

Section: Discussionmentioning

confidence: 99%

Growth inhibitory effects of casein hydrolysates on human cancer cell lines

Phelan

Aherne

O’Sullivan

et al. 2010

Journal of Dairy Research

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The aim of this study was to investigate the effects of unhydrolysed/intact casein and eight different sodium casein hydrolysates (a-h) on the viability and growth of human cancer cell lines. Both human Jurkat T cells and Caco-2 cells were incubated with increasing concentrations of the test compounds (0 . 5-10 % v/v) for 24 h. Cell viability was assessed using the MTT, lactate dehydrogenase (LDH) release and Trypan Blue assays. Cell growth was monitored using the MTT, Trypan Blue and Bromodeoxyuridine (BrdU) proliferation assays. Casein hydrolysates b, c and f had an inhibitory effect on the viability and growth of both cell lines. The casein hydrolysates did not negatively affect the membrane integrity of both Jurkat and Caco-2 cells. In Jurkat cells hydrolysates a and h had an inhibitory effect on DNA synthesis after 24 h, while in Caco-2 cells DNA synthesis was not affected. In conclusion, we found that the different casein hydrolysates had cell-specific effects which target particular functions within the cell. Overall, casein hydrolysates had no effect on membrane integrity while they had varied effects on mitochondrial activity and DNA synthesis in the different cell lines.

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Section: Discussionmentioning

confidence: 99%

Growth inhibitory effects of casein hydrolysates on human cancer cell lines

Phelan

Aherne

O’Sullivan

et al. 2010

Journal of Dairy Research

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“…Therefore, in vitro assays should be furfrom the nominal concentration (added amount of chemical divided by volume of the medium) due to factors such as protein/ lipid binding in the medium Seibert et al, 2002), evaporation, precipitation, and adherence of the chemical to surfaces (Blaauboer, 2010). To determine the in vivo plasma concentration expected to elicit a target-tissue response similar to the cellular response in the in vitro assay, the free fraction must be determined in both the in vitro and in vivo exposures (Gulden et al, 2006;Gulden and Seibert, 2003;Teeguarden and Barton, 2004). To the extent that the cells in the in vitro assay are representative of the cells in the in vivo target tissue, equal free concentration in the medium and plasma will be associated with the same intracellular exposures (Gulden et al, 2001).…”

Section: In Vitro Determination Of Dermal Exposurementioning

confidence: 99%

A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing

Basketter

Clewell

Kimber

et al. 2012

ALTEX

202

165

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“…Before assessing the anti-inflammatory activity, cell viability and the potential cytotoxicity of the LPHs were evaluated (Gülden & Seibert, 2003).…”

Section: Lphs Does Not Alter the Cellular Integrity Of Thp-1-derived mentioning

confidence: 99%

Anti-inflammatory activity of lupine (Lupinus angustifolius L.) protein hydrolysates in THP-1-derived macrophages

Millán-Linares

Bermúdez

Yust

et al. 2014

Journal of Functional Foods

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The effect of two different lupine protein hydrolysates (LPHs) on in vitro macrophage activation in a THP-1-derived macrophage model was investigated. THP-1-derived macrophages were exposed to RPMI medium containing two LPHs obtained by enzymatic hydrolysis using two different proteases: Izyme AL and Alcalase 2.4 L. Cytokine's expression was measured by quantitative PCR. THP-1-derived macrophages exhibited attenuated expression of proinflammatory cytokines (tumour necrosis factor (TNF), IL-6, IL-1β) and increased expression of anti-inflammatory marker genes (chemokine (C-C motif) ligand 18 (CCL18)) relative to control without LPH. The anti-inflammatory effect of both hydrolysates favoured M2 polarization by quenching C-C chemokine receptor type 2 (CCR2) expression and migratory capacity. Furthermore, LPHs significantly decreased nitric oxide production. Moreover, LPHs promoted the survival of human THP-1-derived macrophages. Therefore, inclusion of LPHs in foods may help to prevent chronic diseases associated with chronic inflammation. 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 2 ANTI-INFLAMMATORY ACTIVITY OF LUPINE (Lupinus angustifolius L.) PROTEIN HYDROLYSATES IN THP-1-DERIVED MACROPHAGES AbstractThe effect of two different lupine protein hydrolysates (LPHs) on in vitro macrophage activation in a THP-1-derived macrophage model was investigated. THP-1-derived macrophages were exposed to RPMI medium containing two LPHs obtained by enzymatic hydrolysis using two different proteases: Izyme AL and Alcalase 2.4 L.Cytokine's expression was measured by quantitative PCR. THP-1-derived macrophages exhibited attenuated expression of proinflammatory cytokines (tumour necrosis factor (TNF), IL-6, IL-1β) and increased expression of anti-inflammatory marker genes (chemokine (C-C motif) ligand 18 (CCL18)) relative to control without LPH. The antiinflammatory effect of both hydrolysates favoured M2 polarization by quenching C-C chemokine receptor type 2 (CCR2) expression and migratory capacity. Furthermore, LPHs significantly decreased nitric oxide production. Moreover, LPHs promoted the survival of human THP-1-derived macrophages. Therefore, inclusion of LPHs in foods may help to prevent chronic diseases associated with chronic inflammation.

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In vitro–in vivo extrapolation: estimation of human serum concentrations of chemicals equivalent to cytotoxic concentrations in vitro

Cited by 86 publications

References 20 publications

Growth inhibitory effects of casein hydrolysates on human cancer cell lines

Growth inhibitory effects of casein hydrolysates on human cancer cell lines

A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing

Anti-inflammatory activity of lupine (Lupinus angustifolius L.) protein hydrolysates in THP-1-derived macrophages

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