THE EFFECT OF HALOTHANE INHALATIONAL ANAESTHETICS ON LIVER CELLS(Experimental Study of Halothane Toxic Effect in BALB C Mice) - Diponegoro University | Institutional Repository (UNDIP-IR)
CHAPTER 3
THEORITICAL FRAMEWORK, CONCEPTUAL FRAMEWORK
AND HYPOTHESIS
3.1 Theoretical Framework
Halothane
Induction of
Cytochrom P450
(CYP2E1 and 2A6)
Induction of
Cytochrom P450 (2A6
and 3A4)
Hypoxia
Hepatotoxic metabolites
(bromide and fluoride ions,
other volatil metabolites)
Genotypic and
phenotypic variability
in metabolism,
cytoprotection and
immune response
Increasing Trifluroacetylacid production
binding
Liver protein
Trifluroacetylated
protein
Specific
antibody
Liver cells damage
(nucleus changes: enlarge,
karyorhexis, karyolysis)
Altered liver
antigens
Liver cells necrosis
Moderate / Severe
Liver cells
necrosis
Mild / Severe
Figure 2. Theoretical Framework of the study
26
3.2 Conceptual Framework
Independent Variable
Dependent Variable
Liver cells nucleus changes
(enlarge, karyorhexis,
Halothane
Cytochrome P450 2E1
changes
Figure 3. Conceptual Framework of the study
3.3 Hypothesis
3.3.1
There is an association between the time of halothane exposure with
severity of liver cells nucleus changes
3.3.2
Halothane exposure can induce changes of cytochrome P450 in the
liver
27
THEORITICAL FRAMEWORK, CONCEPTUAL FRAMEWORK
AND HYPOTHESIS
3.1 Theoretical Framework
Halothane
Induction of
Cytochrom P450
(CYP2E1 and 2A6)
Induction of
Cytochrom P450 (2A6
and 3A4)
Hypoxia
Hepatotoxic metabolites
(bromide and fluoride ions,
other volatil metabolites)
Genotypic and
phenotypic variability
in metabolism,
cytoprotection and
immune response
Increasing Trifluroacetylacid production
binding
Liver protein
Trifluroacetylated
protein
Specific
antibody
Liver cells damage
(nucleus changes: enlarge,
karyorhexis, karyolysis)
Altered liver
antigens
Liver cells necrosis
Moderate / Severe
Liver cells
necrosis
Mild / Severe
Figure 2. Theoretical Framework of the study
26
3.2 Conceptual Framework
Independent Variable
Dependent Variable
Liver cells nucleus changes
(enlarge, karyorhexis,
Halothane
Cytochrome P450 2E1
changes
Figure 3. Conceptual Framework of the study
3.3 Hypothesis
3.3.1
There is an association between the time of halothane exposure with
severity of liver cells nucleus changes
3.3.2
Halothane exposure can induce changes of cytochrome P450 in the
liver
27