scholarly journals In Vitro Assays for Phototoxicity

1998 ◽  
Vol 17 (5) ◽  
pp. 567-570
Author(s):  
A. Kornhauser ◽  
R. R. Wei ◽  
W. G. Warner

This paper summarizes a few in vitro methods to assess photodamage in cells irradiated with UV of various wavelengths in the presence of a number of photo-sensitizers. A single in vitro assay for phototoxicity (photoirritation) is not likely to be predictive because of different mechanisms of phototoxicity and diverse cellular targets for injury. A number of methods have to be combined to provide a better prediction of these phenomena. Measurement of mechanistically relevant biomarkers also represents a promising area of in vitro testing for phototoxicity, and it is also briefly reviewed in this paper. Photodynamic sensitizers, representing a large class of phototoxic agents, can now be identified by sensitive measurement of photooxidative damage to cellular RNA and DNA. Currently, US government agencies have not identified a single in vitro assay for phototoxicity which would be acceptable for replacing an in vivo assay for regulatory purposes.

2020 ◽  
Vol 13 (2) ◽  
pp. 123-131
Author(s):  
Steven X. Hu ◽  
Chase A. Mazur ◽  
Kenneth L. Feenstra

Background: There has been a lack of information about the inhibition of bovine medicines on bovine hepatic CYP450 at their commercial doses and dosing routes. Objective: The aim of this work was to assess the inhibition of 43 bovine medicines on bovine hepatic CYP450 using a combination of in vitro assay and Cmax values from pharmacokinetic studies with their commercial doses and dosing routes in the literature. Methods: Those drugs were first evaluated through a single point inhibitory assay at 3 μM in bovine liver microsomes for six specific CYP450 metabolisms, phenacetin o-deethylation, coumarin 7- hydroxylation, tolbutamide 4-hydroxylation, bufuralol 1-hydroxylation, chlorzoxazone 6-hydroxylation and midazolam 1’-hydroxylation. When the inhibition was greater than 20% in the assay, IC50 values were then determined. The potential in vivo bovine hepatic CYP450 inhibition by those drugs was assessed using a combination of the IC50 values and in vivo Cmax values from pharmacokinetic studies at their commercial doses and administration routes in the literature. Results: Fifteen bovine medicines or metabolites showed in vitro inhibition on one or more bovine hepatic CYP450 metabolisms with different IC50 values. Desfuroylceftiour (active metabolite of ceftiofur), nitroxinil and flunixin have the potential to inhibit one of the bovine hepatic CYP450 isoforms in vivo at their commercial doses and administration routes. The rest of the bovine medicines had low risks of in vivo bovine hepatic CYP450 inhibition. Conclusion: This combination of in vitro assay and in vivo Cmax data provides a good approach to assess the inhibition of bovine medicines on bovine hepatic CYP450.


1970 ◽  
Vol 50 (3) ◽  
pp. 557-562 ◽  
Author(s):  
J. E. TROELSEN

Forage of six pure species was harvested for hay at several maturity stages during four years. The digestible energy content of 102 different lots of hay was determined by feeding to four groups of sheep during the same period, and by in vitro digestions and energy analysis of the undigested residues. The relationship between digestible energy content assayed by the two methods was highly significant (r = 0.85) and did not differ between years and species. Exclusion from regression of the hays containing less than 2 or more than 3 digestible kcal/g revealed that the in vitro assay could reproduce the in vivo digestible energy value with a standard deviation of 0.31 in over 70% of the hays. This represented the maturity and quality range of forage commonly fed to cattle and sheep. The in vitro assay therefore appeared promising for commercial quality determinations.


2017 ◽  
Vol 243 (4) ◽  
pp. 375-385 ◽  
Author(s):  
Siti Rosmani Md Zin ◽  
Zahurin Mohamed ◽  
Mohammed A Alshawsh ◽  
Won F Wong ◽  
Normadiah M Kassim

Anastatica hierochuntica L. ( A. hierochuntica), a folk medicinal plant, was evaluated for mutagenic potential via in vitro and in vivo assays. The in vitro assay was conducted according to modified Ames test, while the in vivo study was performed according to Organisation for Economic Co-operation and Development guideline for mammalian erythrocyte micronucleus assay. Four groups ( n= 5 males and 5 females per group) Sprague Dawley rats were randomly chosen as the negative control, positive control (received a single intramuscular injection of cyclophosphamide 50 mg/kg), 1000 and, 2000 mg/kg A. hierochuntica aqueous extracts. All groups except the positive control were treated orally for three days. Findings of the in vitro assay showed mutagenic potential of AHAE at 0.04 and 0.2 mg/ml. However, no mutagenic effect was demonstrated in the in vivo study up to 2000 mg/kg. No significant reduction in the polychromatic and normochromatic erythrocytes ratio was noted in any of the groups. Meanwhile, high micronucleated polychromatic erythrocytes frequency was seen in cyclophosphamide-treated group only. These findings could perhaps be due to insufficient dosage of A. hierochuntica aqueous extracts to cause genetic damage on the bone marrow target cells. Further acute and chronic in vivo toxicity studies may be required to draw pertinent conclusion on the safety aspect of A. hierochuntica aqueous extracts consumption. Impact statement In this paper, we report on the mutagenicity evaluation of Anastatica hierochuntica aqueous extract. This is a significant research in view of the popularity of this herb consumption by the people across the globe despite of limited scientific evidence on its toxicity potential. This study is intended to encourage more extensive related research in order to provide sufficient evidence and guidance for determining its safe dosage.


2005 ◽  
Vol 187 (10) ◽  
pp. 3374-3383 ◽  
Author(s):  
Christopher Stead ◽  
An Tran ◽  
Donald Ferguson ◽  
Sara McGrath ◽  
Robert Cotter ◽  
...  

ABSTRACT The lipid A domain anchors lipopolysaccharide (LPS) to the outer membrane and is typically a disaccharide of glucosamine that is both acylated and phosphorylated. The core and O-antigen carbohydrate domains are linked to the lipid A moiety through the eight-carbon sugar 3-deoxy-d-manno-octulosonic acid known as Kdo. Helicobacter pylori LPS has been characterized as having a single Kdo residue attached to lipid A, predicting in vivo a monofunctional Kdo transferase (WaaA). However, using an in vitro assay system we demonstrate that H. pylori WaaA is a bifunctional enzyme transferring two Kdo sugars to the tetra-acylated lipid A precursor lipid IVA. In the present work we report the discovery of a Kdo hydrolase in membranes of H. pylori capable of removing the outer Kdo sugar from Kdo2-lipid A. Enzymatic removal of the Kdo group was dependent upon prior removal of the 1-phosphate group from the lipid A domain, and mass spectrometric analysis of the reaction product confirmed the enzymatic removal of a single Kdo residue by the Kdo-trimming enzyme. This is the first characterization of a Kdo hydrolase involved in the modification of gram-negative bacterial LPS.


Chemosphere ◽  
1992 ◽  
Vol 25 (7-10) ◽  
pp. 1085-1090 ◽  
Author(s):  
T. Massa ◽  
A. Esmseili ◽  
H. Fortmeyer ◽  
B. Schlatterer ◽  
H. Hagenmaier ◽  
...  

2019 ◽  
Vol 64 (No. 7) ◽  
pp. 294-301
Author(s):  
S Gonzalez-Munoz ◽  
J Sanchez ◽  
S Lopez-Aguirre ◽  
J Vicente ◽  
J Pinos-Rodriguez

One in vitro assay and one in vivo trial with ruminally cannulated Holstein steers were conducted to evaluate the effects of a dietary substitution of soybean meal by a urea and slow-release urea source of fermentation and degradation of diets for cattle. The experimental diets consisted of the total mixed rations defined as the control with soybean meal (SBM), U (urea), SRU (slow-release urea), and SRU+U+AA (0.42% + 0.42% + 1% amino acids methionine and lysine). The dietary substitution of SBM by U or SRU reduced (P < 0.05) the total gas production (V), microbial mass and degradation at 72 h incubation under the in vitro conditions, as well as the degradation rate (c) and the total volatile fatty acids (VFA) in the rumen of the steers; however, when the dietary substitution of SBM was by U+SRU+AA, those values did not decrease. In the steers, the dietary substitution of SBM by U and SRU reduced the ruminal degradation rate and the total VFA, and increased the ammonia N, but when SBM was substituted by U+SRU+AA in the diets, these changes were not observed. No advantage of SRU over U was found. The dietary substitution of SBM by U, SRU, U+SRU+AA did not modify the molar proportion of the VFA in the rumen nor were there changes in the nutrient digestion or excretion. Both the in vitro assay and the in vivo trial indicated that replacing SBM with U or SRU increases the ruminal ammonia N concentrations and reduces the degradation rate in the rumen, although those undesirable findings were not found when the SBM was replaced by U+SRU+AA. Therefore, it is feasible to replace the SBM with a combination of urea, slow-release urea, lysine and methionine in the diet for the ruminants.


1963 ◽  
Vol 157 (5) ◽  
pp. 785-797 ◽  
Author(s):  
G. O. McDonald ◽  
A. N. Stroud ◽  
A. M. Brues ◽  
W. H. Cole

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