scholarly journals Defining in vivo dose‐response curves for kidney DNA adduct formation of aristolochic acid I in rat, mouse and human by an in vitro and physiologically based kinetic modeling approach

2020 ◽  
Vol 40 (12) ◽  
pp. 1647-1660
Author(s):  
Rozaini Abdullah ◽  
Sebastiaan Wesseling ◽  
Bert Spenkelink ◽  
Jochem Louisse ◽  
Ans Punt ◽  
...  
Keyword(s):  
Kinetic Modeling ◽  
Dose Response ◽  
Aristolochic Acid ◽  
Adduct Formation ◽  
Dna Adduct ◽  
Response Curves ◽  
Physiologically Based ◽  
Aristolochic Acid I

DNA adduct formation of aristolochic acid I and II in vitro and in vivo

1988 ◽  
Vol 9 (2) ◽  
pp. 297-303 ◽  
Author(s):  
H.H. Schmeiser ◽  
K.-B. Schoepe ◽  
M. Wiessler
Keyword(s):  
Aristolochic Acid ◽  
Adduct Formation ◽  
Dna Adduct ◽  
Aristolochic Acid I

scholarly journals The Use of In Vitro Toxicity Data and Physiologically Based Kinetic Modeling to Predict Dose-Response Curves for In Vivo Developmental Toxicity of Glycol Ethers in Rat and Man

2010 ◽  
Vol 118 (2) ◽  
pp. 470-484 ◽  
Author(s):  
Jochem Louisse ◽  
Esther de Jong ◽  
Johannes J. M. van de Sandt ◽  
Bas J. Blaauboer ◽  
Ruud A. Woutersen ◽  
...  
Keyword(s):  
Kinetic Modeling ◽  
Dose Response ◽  
Developmental Toxicity ◽  
In Vitro Toxicity ◽  
Toxicity Data ◽  
Glycol Ethers ◽  
Response Curves ◽  
Physiologically Based

Differences in in vivo and in vitro sequence-specific sites of cisplatin-DNA adduct formation and detection of a dose-response relationship

1994 ◽  
Vol 48 (1) ◽  
pp. 145-153 ◽  
Author(s):  
Glenn J. Bubley ◽  
Beverly A. Teicher ◽  
George K. Ogata ◽  
Larue S. Sandoval ◽  
Tetsuya Kusumoto
Keyword(s):  
Dose Response ◽  
Adduct Formation ◽  
Dna Adduct ◽  
Response Relationship ◽  
Dose Response Relationship

scholarly journals Physiologically based kinetic modelling based prediction of in vivo rat and human acetylcholinesterase (AChE) inhibition upon exposure to diazinon

2021 ◽  
Author(s):  
Shensheng Zhao ◽  
Sebastiaan Wesseling ◽  
Bert Spenkelink ◽  
Ivonne M. C. M. Rietjens
Keyword(s):  
Dose Response ◽  
Kinetic Modelling ◽  
Ache Inhibition ◽  
Response Curves ◽  
Alternative Testing ◽  
Dose Response Curves ◽  
Physiologically Based Kinetic Modelling ◽  
Point Of Departure

AbstractThe present study predicts in vivo human and rat red blood cell (RBC) acetylcholinesterase (AChE) inhibition upon diazinon (DZN) exposure using physiological based kinetic (PBK) modelling-facilitated reverse dosimetry. Due to the fact that both DZN and its oxon metabolite diazoxon (DZO) can inhibit AChE, a toxic equivalency factor (TEF) was included in the PBK model to combine the effect of DZN and DZO when predicting in vivo AChE inhibition. The PBK models were defined based on kinetic constants derived from in vitro incubations with liver fractions or plasma of rat and human, and were used to translate in vitro concentration–response curves for AChE inhibition obtained in the current study to predicted in vivo dose–response curves. The predicted dose–response curves for rat matched available in vivo data on AChE inhibition, and the benchmark dose lower confidence limits for 10% inhibition (BMDL10 values) were in line with the reported BMDL10 values. Humans were predicted to be 6-fold more sensitive than rats in terms of AChE inhibition, mainly because of inter-species differences in toxicokinetics. It is concluded that the TEF-coded DZN PBK model combined with quantitative in vitro to in vivo extrapolation (QIVIVE) provides an adequate approach to predict RBC AChE inhibition upon acute oral DZN exposure, and can provide an alternative testing strategy for derivation of a point of departure (POD) in risk assessment.

Histamine tachyphylaxis in canine airways despite prostaglandin synthesis inhibition

1988 ◽  
Vol 65 (5) ◽  
pp. 1944-1949 ◽  
Author(s):  
P. J. Antol ◽  
S. J. Gunst ◽  
R. E. Hyatt
Keyword(s):  
Smooth Muscle ◽  
Dose Response ◽  
Prostaglandin Synthesis ◽  
Response Curves ◽  
Synthesis Inhibition ◽  
High Concentrations ◽  
Alpha Chloralose ◽  
Prostaglandin Synthesis Inhibitors

Tachyphylaxis to aerosolized histamine was studied in dogs anesthetized with thiamylal after pretreatment with prostaglandin synthesis inhibitors. Three consecutive histamine dose-response curves were obtained in nine dogs pretreated with 5 mg/kg indomethacin; two of these nine were also pretreated with 10 mg/kg indomethacin. Seven of the nine dogs were pretreated with 4 mg/kg sodium meclofenamate; four of these seven were also pretreated with 12 mg/kg. All dogs had tachyphylaxis at high concentrations of histamine regardless of inhibitor used. Pretreatment with indomethacin while the dogs were under alpha-chloralose-urethan anesthesia gave similar results. Histamine tachyphylaxis was also studied both in the presence and in the absence of indomethacin in tracheal smooth muscle strips obtained from seven additional dogs. A decrease in the median effective dose to histamine was observed in the indomethacin-treated strips, but tachyphylaxis to histamine remained. We conclude that prostaglandin synthesis inhibition does not reverse histamine tachyphylaxis either in vivo or in vitro. Thus the mechanism of histamine tachyphylaxis remains unexplained.

Histamine H2-receptor of human and rabbit parietal cells

1987 ◽  
Vol 253 (4) ◽  
pp. G497-G501 ◽  
Author(s):  
R. Leth ◽  
B. Elander ◽  
U. Haglund ◽  
L. Olbe ◽  
E. Fellenius
Keyword(s):  
Dose Response ◽  
In Vivo Model ◽  
Response Curves ◽  
Gastric Glands ◽  
Histamine H2 Receptor ◽  
Receptor Affinity ◽  
H2 Receptor ◽  
Dose Response Curves

The histamine H2-receptor on the human parietal cell has been characterized by using dose-response curves and the negative logarithm of the molar concentration of an antagonist (pA2) analyses of cimetidine antagonism of betazole, histamine, and impromidine stimulation in isolated human and rabbit gastric glands. To evaluate the in vitro results, betazole-stimulated gastric acid secretion with and without cimetidine was also studied in healthy subjects. In the in vivo model, individual dose-response curves were shifted to the right with increasing cimetidine concentrations, but this was counteracted by increasing betazole doses, indicating competitive, reversible antagonism. The pA2 values ranged from 6.1 to 6.3. In isolated human gastric glands, impromidine was shown to be eight times more potent than histamine, indicating higher receptor affinity, but the maximally stimulated aminopyrine accumulation was the same as for histamine, and the pA2 values for cimetidine antagonism did not differ significantly, i.e., 5.7 (histamine) and 6.1 (impromidine). In isolated rabbit gastric glands, cimetidine inhibited the histamine- and impromidine-stimulated response with pA2 values of 6.0 and 7.3, respectively. Impromidine was shown to be approximately 100 times more potent than in human gastric glands, whereas histamine had the same potency. This confirms the role of the histamine H2-receptor and suggests a difference between the species concerning receptor affinity.

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