Calculating slope and ED50 of additive dose-response curves, and application of these tabulated parameter values

Pöch, G.; Pancheva, S

doi:10.1016/1056-8719(94)00068-f

Cited by 21 publications

(13 citation statements)

References 9 publications

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“…Indeed, the scientific literature contains many publications describing methods for conducting interaction studies. Some examples that provide methodological background include: (Berenbaum 1978(Berenbaum , 1981(Berenbaum , 1984(Berenbaum , 1985(Berenbaum , 1989Carter et al 1979;Carter et al 1984;Carter and Wampler 1986;Caudle and Williams 1993;Chou and Talalay 1984;Gennings 1995Gennings , 1996Gennings et al 1990;Gessner 1995;Greco et al 1995;Greco et al 1990;Loewe and Muischnek 1926;Machado and Robinson 1994;Martinez-Irujo et al 1996;Poch 1980a,b;Poch et al1990a;Poch and Holzmann 1980;Londong 1985, 1993;Poch and Pancheva 1995;Poch et al 1995a. ;Poch et al 1990;Poch et al1990b;Scaramellini et al 1997;Suhnel 1990Suhnel , 1996 200350.pgs 4/13/01, 2:31 PM…”

Section: Introductionmentioning

confidence: 99%

Evaluating Chemical Interaction Studies for Mixture Risk Assessment

Borgert

Price

Wells

et al. 2001

Human and Ecological Risk Assessment: An International Journal

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We describe a set of criteria to evaluate the quality of data and interpretations in chemical interaction studies. These criteria reflect the consensus of the literature on interaction analysis developed over decades of research in pharmacology, toxicology, and biometry; address common pitfalls in published interaction studies; and can be easily applied to common methods of interaction analysis. The criteria apply broadly to interaction data for drugs, pesticides, industrial chemicals, food additives, and natural products and are intended to assist risk assessors who must evaluate interaction studies for use in component-based mixture risk assessments. The criteria may also assist researchers interested in conducting interaction studies to inform mixture risk assessment. The criteria are also intended to serve larger scientific goals, including increasing the repeatability of results obtained in chemical interaction studies, enhancing the reliability of conclusions drawn from interaction data, providing greater consistency of interpretations among various analysts, and decreasing uncertainty in using interaction data in risk assessments. We describe the basis for each criterion and demonstrate their utility by using them to evaluate interaction studies from the recent toxicological and pharmacological literature, which serve as examples of different types of data sets that the risk assessor may encounter.

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Section: Introductionmentioning

confidence: 99%

Evaluating Chemical Interaction Studies for Mixture Risk Assessment

Borgert

Price

Wells

et al. 2001

Human and Ecological Risk Assessment: An International Journal

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“…EC 50 values were obtained from these equations. To measure additive effects of IPI and TCDD or FICZ on EROD we compared the observed effects of the combinations to theoretical best fit curves for additive agonists based on the model of Poch and Pancheva [12]. Statistical comparisons of theoretical and best-fit curves were performed using the extra sum-of-squares F test.…”

Section: Methodsmentioning

confidence: 99%

Discovery and biological characterization of 1-(1H-indol-3-yl)-9H-pyrido[3,4-b]indole as an aryl hydrocarbon receptor activator generated by photoactivation of tryptophan by sunlight

Diani-Moore

Labitzke

et al. 2011

Chemico-Biological Interactions

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Activation of the aryl hydrocarbon receptor (AHR) by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is required for AHR dependent transcriptional activation and TCDD toxicity. We previously reported that aqueous tryptophan exposed to sunlight through window glass (aTRP) contains multiple photoproducts, including the well characterized 6-formylindolo[3,2-b]carbazole (FICZ), capable of activating the AHR and inducing CYP1A and CYP1A-mediated enzyme activities. We report here the isolation from aTRP and chemical characterization and synthesis of 1-(1H-indol-3-yl)-9H-pyrido[3,4-b]indole (IPI), a compound previously identified as a natural product of marine ascidia and now shown to be a TRP photoproduct with AHR-inducing properties. IPI, FICZ and TCDD produced equieffective induction of CYP1A-mediated 7-ethoxyresorufin deethylase (EROD) activity in chick embryo primary hepatocytes and mammalian Hepa1c1c7 cells. EROD induction by IPI was markedly curtailed in AHR-defective c35 cells, supporting the AHR dependence of the IPI response. Although IPI had a higher EC50 for EROD induction than FICZ, the much larger amount of IPI than FICZ in aTRP makes IPI a prominent contributor to EROD induction in aTRP. IPI was detected in TRP-containing culture medium under ambient laboratory conditions but not in TRP-free medium, consistent with its production from TRP. Cotreatment of hepatocytes with submaximal EROD-inducing doses of IPI and FICZ or TCDD produced additive increases in EROD without synergistic or inhibitory interactions. IPI and FICZ were readily metabolized by cultured hepatocytes. In addition to increasing CYP1A4 mRNA and EROD, IPI and FICZ decreased hepatocyte phosphoenolpyruvate carboxykinase mRNA expression and glucose output, biological effects associated with TCDD metabolic dysregulation. The findings underscore a role for sunlight in generating AHR-activating bioactive molecules.

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“…4 In line with our previous in vivo experiments, in vitro cotreatment of heart cells with DFO and PIH analogs had an improved iron-mobilizing effect. To analyze the dose-response profiles of the drug combinations used, we followed the methods described by Poch et al [26][27][28] The use of model combination effects for the delineation of sites and mechanisms of action requires some understanding of the underlying bases of these models. The dose-additivity model describes the combination effects of agents that share the same molecular site of action.…”

Section: Discussionmentioning

confidence: 99%

“…Dose-response profiles of the combination of drugs was subjected to quantitative analysis based on the methods described by Poch et al [26][27][28] Five-day-old cultures were first incubated with 160 M 59 Fe-labeled ferric ammonium citrate for 24 hours, washed, and exposed for another 24 hours to 20 or 40 M DFO and 0 to 160 M 108-o. The effect was described as percentage of initial radioactivity in control iron-loaded cells.…”

Section: Studies In Cultured Heart Cellsmentioning

confidence: 99%

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Effects of combined chelation treatment with pyridoxal isonicotinoyl hydrazone analogs and deferoxamine in hypertransfused rats and in iron-loaded rat heart cells

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Ponka

Konijn

et al. 2003

Blood

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Although iron chelation therapy with deferoxamine (DFO) results in improved life expectancy of patients with thalassemia, compliance with parenteral DFO treatment is unsatisfactory, underlining the need for alternative drugs and innovative ways of drug administration. We examined the chelating potential of pyridoxal isonicotinoyl hydrazone (PIH) analogs, alone or in combination with DFO, using hypertansfused rats with labeled hepatocellular iron stores and cultured ironloaded rat heart cells. Our in vivo studies using 2 representative PIH analogs, 108-o and 109-o, have shown that PIH analogs given orally are 2.6 to 2.8 times more effective in mobilizing hepatocellular iron in rats, on a weight-per-weight basis, than parenteral DFO administered intraperitoneally. The combined effect of DFO and 108-o on hepatocellular iron excretion was additive, and response at a dose range of 25 to 200 mg/kg was linear. In vitro studies in heart cells showed that DFO was more effective in heart cell iron mobilization than all PIH analogs studied. Response to joint chelation with DFO and PIH analogs was similar to an increase in the equivalent molar dose of DFO alone, rather than the sum of the separate effects of the PIH analog and DFO. This finding was most likely the result of iron transfer from PIH analogs to DFO, a conclusion supported directly by iron-shuttle experiments using fluorescent DFO. These findings provide a rationale for the combined, simultaneous use of ironchelating drugs and may have useful, practical implications for designing novel strategies of iron chelation therapy.

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Calculating slope and ED50 of additive dose-response curves, and application of these tabulated parameter values

Cited by 21 publications

References 9 publications

Evaluating Chemical Interaction Studies for Mixture Risk Assessment

Evaluating Chemical Interaction Studies for Mixture Risk Assessment

Discovery and biological characterization of 1-(1H-indol-3-yl)-9H-pyrido[3,4-b]indole as an aryl hydrocarbon receptor activator generated by photoactivation of tryptophan by sunlight

Effects of combined chelation treatment with pyridoxal isonicotinoyl hydrazone analogs and deferoxamine in hypertransfused rats and in iron-loaded rat heart cells

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