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Additional toxicological data

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Administrative data

Endpoint:
additional toxicological information
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
unsuitable test system
Remarks:
irrelevant route of exposure.

Data source

Reference
Reference Type:
publication
Title:
Differential effects of 3 dipyridyl isomers on hepatic microsomal cytochrome P450 and heme oxygenase in rats
Author:
Yoshida T, Kobayashi Y, Masuko T, Hashimoto Y, Kuroiwa Y
Year:
1995
Bibliographic source:
Toxicol Lett. 1995, 76(2):145-53; PMID: 7725346

Materials and methods

Type of study / information:
Effect of 2,2'-bipyridine on xenobiotic-metabolizing enzymes of rat liver after i.p. administration.
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Male Wistar rats received a single i.p. injection of the test item 2,2'-bipyridine (15.6-125.0 mg/kg bw) dissolved in corn oil and were decapitated 24 h later. Glutathione content was determined from liver which was cut off before liver perfusion was performed. Cytochrome P450 content and activity of different enzymes were measured from liver cell homogenate.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2,2'-bipyridyl
EC Number:
206-674-4
EC Name:
2,2'-bipyridyl
Cas Number:
366-18-7
Molecular formula:
C10H8N2
IUPAC Name:
2,2'-bipyridyl
Details on test material:
- Name of test material (as cited in study report): 2,2'-bipyridyl

Results and discussion

Any other information on results incl. tables

The test item 2,2'-bipyridine slightly increased rat liver CYP content in the low-dose group (15.6 mg/kg bw) but decreased CYP content with increasing dose levels. In the Western Blot analysis, 2,2'-bipyridine showed no effect neither on CYP 1A1/2 nor on CYP 2B1/2 expression.

The activity of the drug-metabolizing enzymes aminopyrine demethylase, aniline hydroxylase, and dimethylnitrosamine demethylase was slightly but significantly increased at lower dose levels (15.6 -31.2 mg/kg bw) but declined at higher concentrations.

Heme oxygenase activity and GSH content of rat liver was significantly increased in a dose-dependant manner after treatment with 2,2'-bipyridine. Experiments with cycloheximide (an inhibitor of protein biosynthesis) revealed that increased enzyme activity was due to de novo protein synthesis (data not shown).

 

Table 1: Dose response of 2,2’-bipyridine on drug-metabolizing enzyme activities, heme oxygenase activity and GSH content in rat liver, mean ± SD of 4-6 rats.

Dose [mg/kg]

Aminopyrine demethylase [nmol/mg protein/min]

Aniline hydroxylase [nmol/mg protein/min]

Dimethylnitrosamine demethylase [nmol/mg protein/min]

Heme oxygenase [nmol/mg protein/h]

GSH content [µmol/g liver]

Control

5.575±0.072

1.716±0.015

1.782±0.015

1.849±0.056

4.153±0.283

15.6

9.501±0.382**

2.204±0.035**

2.371±0.148**

2.141±0.109*

4.321±0.097

31.2

8.901±0.722**

2.200±0.301*

2.364±0.087**

3.914±0.268**

4.543±0.295

62.5

6.896±0.136**

1.478±0.050**

1.349±0.188**

10.979±0.399**

7.976±0.189**

93.7

4.336±0.522**

1.161±0.130**

1.095±0.007**

20.945±0.112**

10.745±0.747**

124.9

3.300±0.082**

0.838±0.007**

0.641±0.041**

27.295±0.545**

10.657±0.359**

 

 

Applicant's summary and conclusion

Conclusions:
Administration of 2,2'-bipyridyl in corn oil to rats via i.p. injection resulted in a concentration-dependant increase of hepatic heme oxygenase activity and glutathione content. The content of cytochrome P450 and of the drug-metabolizing enzymes aminopyrine demethylase, aniline hydroxylase, and dimethylnitrosamine demethylase firstly increased but then declined at higher concentrations.
Executive summary:

Male Wistar rats received a single i.p. injection of the test item 2,2'-bipyridine (15.6-125.0 mg/kg bw) dissolved in corn oil and were decapitated 24 h later. Glutathione content was determined from liver which was cut off before liver perfusion was performed. Cytochrome P450 content and activity of different enzymes were measured from liver cell homogenate.

Administration of 2,2'-bipyridyl in corn oil to rats via i.p. injection resulted in a concentration-dependant increase of hepatic heme oxygenase activity and glutathione content. The content of cytochrome P450 and of the drug-metabolizing enzymes aminopyrine demethylase, aniline hydroxylase, and dimethylnitrosamine demethylase firstly increased but then declined at higher concentrations.

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