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DOI 10.11603/ijmmr.2413-6077.2016.1.6379

ENZYmE mARKERs AcTIVITY ANd BILE fORmATION fUNcTION 
Of LIVER IN cAsEs Of TUBERcULOsTATIcs ANd hEXAVALENT 
chROmIUm cOmPOUNds AffEcTION IN RATs

n. I. Burmas, L. S. Fira, P. H. Lyhackyy
I. HORBACHEVSKY TERNOPIL STATE MEDICAL UNIVERSITY, TERNOPIL, UKRAINE

Background. Currently, the growing incidence of toxic lesions of the liver is associated with 
industrial chemicalization and uncontrolled use of hepatotoxic drugs in everyday life. There are about 
one thousand drugs with high or low hepatotoxicity, such as anti-TB drugs.

Objective. In this research we studied the intracellular enzymes activity and bile formation function 
of the liver in rats of different ages in cases of tuberculostatic (isoniazid and rifampicin) affection and 
chromium (potassium dichromate) intoxication.

Methods. The experimental affection of rats of different ages was performed by combined injection 
of hexavalent chromium compounds (a solution of potassium dichromate, 3 mg/kg), isoniazid  
(0.05 g/kg) and rifampicin (0.25 g/kg). On the 7th and 14th days the rats were injected with enterosorbent 
Sorbex (150 mg/kg). Enzyme markers activity of the liver was evaluated due to alanine and aspartate 
aminotransferases (ALT and AST) and alkaline phosphatase (ALP) rates. Bile formation function of the 
liver was evaluated by total bilirubin and bile acids content in blood. 

Results. The disorders in hepatocytes plasma membranes permeability were defined by the 
increased rates of ALT, AST and alkaline phosphatase in blood serum which were decreased in the 
liver. It was determined that total bilirubin and bile acids content in blood serum of the affected 
animals increased. It influenced hepatocytes excretion in bile capillaries and caused cholestasis and 
revenues decrease in bile. 

Conclusions. The most significant metabolic disorders in cases of chrome-isoniazid-rifampicin 
affection were defined in immature and senior animals in comparison with mature animals. 

KEY WORDS: isoniazid, rifampicin, hexavalent chromium compounds, liver enzymes, 
bile formation.

N. I. burmas et al.

Address for correspondence: Nataliya Burmas, Department of 
General Chemistry, I. Horbachevsky Ternopil State Medical 
University, 1 Maidan Voli, Ternopil, Ukraine, 46001 
Tel.: +380976123434 
E-mail: burmas@tdmu.edu.ua

Introduction
Considering the role of liver in the chemical 

compounds metabolism we can assert that 
there are no drugs that in certain conditions 
would not cause impairment. More and more 
information about their hepatotoxic effect 
indicates that medical affection of the liver is 
one of the major problems of hepatology [1–3]. 
Antituberculosis drugs are of great interest 
[4–6]. 

According to the Centre of monitoring of 
adverse reactions of drugs (2007), isoniazid – 
29.2%, rifampicin – 26.7%, capreomycin – 17.1%, 
ethambutol – 10.2% dominate among mono-
preparations in high incidence of the adverse 

reactions in world [5]. Thus, the risk of the 
development of hepatitis increases in patients 
who take rifampicin together with isoniazid. In 
this case hepatitis incidence is 5-8%. During the 
isoniazid monotherapy, the incidence of hepa-
titis is 1.2%, but during the rifampin monothe-
rapy – 0.3% [4]. 

According to the researches [7, 8], the hepa-
totoxicity of isoniazid may be developed in two 
ways: 1. the accumulation of free radicals with 
activation of lipid peroxidation and the formation 
of reactive metabolites: acetylisoniazid, hydra-
zine, monoacetylhydrazine; 2. the increased 
activity of N-acetylisoniazid by N-hydroxylation 
and formation of acetyl radical and acetyl car-
bonium ion.

The metabolism of acetyl hydrazine and 
microsomal monooxygenases cause hepatotoxic 
effect as a result of the covalent addition of 

International Journal of Medicine and Medical Research 
2016, Volume 2, Issue 1, p. 32–38
copyright © 2016, TSMU, All Rights Reserved



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acetyl groups to the liver proteins [7], which 
manifest as temporary asymptomatic increase 
of transaminases activity. The hepatotoxicity of 
rifampin is also due to the formation of toxic 
metabolites as a result of its deacetylation in 
the liver that leads to hepatocytes dystrophy 
[9, 10].

However, increasing saturation of the envi-
ronment by the compounds of heavy metals 
leads to the accumulation of these compounds 
in human bodies, of those who live on the con-
taminated areas from early childhood [11–13]. 
According to some studies, in the future the 
compounds of heavy metals as the threat for 
the environment can become the urgent 
matter, leaving nuclear stations wastes and 
organic anthropogenic pollution behind [13].

Today Chromium (VI) is recognized by the 
International Agency of the Cancer Researches 
of the European Union to be one of six chemical 
elements (Arsenic, Beryllium, Cadmium, Cobalt, 
Nickel and Chromium) that reveal the carci no-
genic effect on human body [14, 15]. The influ-
ence of the compounds of Chromium (VI) is 
accompanied by toxic effects and serious inter-
nal organs (kidneys, lungs, liver) da mage.

But, the recent studies do not provide full 
concept of the of liver enzymes activity and its 
influence on bile formation function in cases of 
combined effect of hexavalent chromium com-
pounds on age-dependent isoniazid-rifampicin 
destruction of the body, which is presented in 
this research.

Materials and Methods 
The experiments were conducted on out-

bred white male rats of three age groups: the 
1st group – immature (3-month-old animals, 
90–110 g in weight); 2nd group – mature 
(6-month-old animals, 150–170 g in weight); 
and the 3rd group – senile (18-months-old ani-
mals, 280–300 g in weight). The rats were kept 
on a standard diet at the vivarium of Ter nopil 
State Medical University.

The manipulations on the animals were 
carried out according to the Article 26 of the 
Law of Ukraine “On protection of cruelty to 
ani mals” from 21.02.2006. No. 3447-IV, “Euro-
pean Convention on protection of vertebrate 
animals used for experimental and other scien-
tific purposes”, “General ethical principles of 
the experiments on animals", approved 
20.09.2001 during the 1st Ukrainian National 
Con gress on Bioethics considering regulations 
of NIH Guide on Care and Use of Laboratory 
Animals [16].

The experimental toxic affection of the ani-
mals was simulated by combined effect of 
hexavalent chromium compounds, isoniazid 
and rifampicin. Hexavalent chromium com-
pounds were administered intragastrically to 
animals every day for one group by the solution 
of potassium dichromate, 3 mg/kg. For another 
group on the 7th and 14th days isoniazid and 
rifampicin by metallic probe in aqueous solu-
tion, 0.05 g/kg and 0.25 g/kg accordingly, were 
administered intragastrically. For combined 
action, the xenobiotics mentioned above were 
administered in the same doses.

Euthanasia was performed by means of 
thiopental sodium on the 7th and 14th days from 
the first day of xenobiotics administration. The 
study of liver homogenate and blood serum 
was performed. The blood was taken from the 
heart of animals by centrifugation at 3000 rev/
min during 30 min. The obtained blood serum, 
sedimentary liquid, was used for researches. 
Liver (250 mg) was put into 10% homogenate 
and different homogenisation methods were 
used after previous perfusion in physiological 
solution. 

The activity of liver enzyme markers was 
determined by the rate of aminotransferases 
(ALT and AST) and an alkaline phosphatase 
(ALP) (the reagents of OOO NPP Filisit- Diag-
nostics, Ukraine) in blood serum and liver 
homogenate. The evaluation of ALT rate was 
conducted by compound of 2-oxoglutaric acid 
and L-alanine, which under the influence of 
alanine aminotransferase formed L-glutamic 
and pyruvic acids. The interaction of pyruvic 
acid and 2.4-dynitrophenylhydrazine in alkaline 
medium formed 2.4-dynitrophenylhydrazones 
that had high coefficient of the molar extinction, 
so its optical density registered on the FEC was 
directly proportional to the activity of the 
enzyme.

The enzyme activity was estimated by the 
calibration graph due to the content of pyruvic 
acid in mkmol/(L∙h) [17]. AST rate was evaluated 
by optical density measuring of 2.4 nitro phe-
nylhydrazones of 2-oxoglutaric and pyruvic 
acids in alkaline medium. Hydrazone of pyruvic 
acid has a higher coefficient of the molar extinc-
tion, so there is a directly proportional rela-
tionship of optical density of the reaction 
solution to the enzyme activity. The enzyme 
activity was evaluated by the calibration graph 
due to the content of pyruvic acid, mkmol/(L∙h) 
[17]. Estimation of the alkaline phosphatase 
rate was based on the property of the enzyme 
to hydrolyse the etheric bond in β-glycero-

N. I. burmas et al.



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phosphate and eliminate the phosphoric acid. 
Phosphorus was determined by colorimetric 
method due to the reaction with molybdenum 
reagent in the presence of a reducing eikonogen 
or ascorbic acid. The product of reaction was 
molybdenum blue; its colour intensity was 
directly proportional to the amount of phos-
phorus in the simple evaluation of the enzyme 
activity [18].

The bile formation function of the liver in 
the animals was defined by the content of total 
bilirubin and bile acids in blood serum. The 
content of total bilirubin was determined by 
caffeine reagent, which together with diazotized 
sulphanilic acid formed azobilirubin of pink-
purple colour. The colour intensity of this solu-
tion was directly proportional to the concen-
tration of total bilirubin in the sample. Evaluation 
of total bilirubin in blood serum was performed 
by the calibration graph, mmol/L [18]. Deter-
mination of bile acids content was based on the 
reaction of colour products formation by 
condensation, which interacted with bile acids 
and oxymethyl furfural. These solutions were 
obtained from fructose. They are the products 
of hydrolysis by adding concentrated sulfuric 
acid to sucrose. Bile acids content was evaluated 
by the calibration graph due to the tauroholic 
acid content, g/L [18].

The statistical processing of the results was 
performed on a PC by means of programs 
"Microsoft Excel" and "STATISTICA 6.0" on the 

basis of arithmetic middling and errors accor-
ding to Student's t-test [19]. The changes were 
considered to be reliable at p≤0.05.

Results 
We noted the increased ALT rate (Table 1) 

in the blood serum of animal groups of all ages. 
It was the highest in rats affected by tubercu-
lostatics and potassium dichromate. On the 14th 
day of xenobiotics administration the rate 
increased in 2.9 times in immature animals in 
comparison with the control group, in 2.5 
times – in mature animals and in 3.2 times – in 
senior animals. The mature animals, which 
were affected by hexavalent chromium com-
pounds, proved to be the least sensitive. Their 
affection rate exceeded the normal range in 2.3 
times.

In the immature rats the ALT rate increased 
by 120% on the 7th day of the research and by 
145% – on the 14th day of the affection by iso-
niazid and rifampicin, in the mature animals 
this rate exceeded the level of the intact control 
by 30% on the 7th day and by 128% till the end 
of the experiment.

The senior animals were more sensitive to 
anti-TB drugs. ALT rate in blood serum in-
creased by 181% on the 14th day after the affec-
tion.

The most significant changes were ob-
served in the liver of the senior animals which 
underwent the aforementioned xenobiotics 

Table 1. Alanine aminotransferase rate in blood serum (mkmol/L·h) and liver (mkmol/kg·h)  
of rats affected by isoniazid, rifampicin and hexavalent chromium compounds, (M±m) 

Research 
material Group of animals

Age group of animals
immature mature senior

Research duration, days
7th 14th 7th 14th 7th 14th

blood 
serum 

intact control, n=6 0.83±0.05 2.96±0.18 2.34±0.15
affected by potassium  

dichromate, n=6
1.51±
0.10*

1.93±
0.16*

4.03±
0.32*

6.66±
0.17*

3.75±
0.36*

6.16±
0.37*

affected by isoniazid  
and rifampicin, n=6

1.83±
0.11*

2.03±
0.20*

3.84±
0.24*

6.74±
0.26*

4.44±
0.32*

6.58±
0.30*

affected by potassium 
dichromate, isoniazid 
and rifampicin, n=6

2.21±
0.12*

2.38±
0.14*

4.69±
0.19*

7.46±
0.42*

5.87±
0.30*

7.57±
0.26*

liver intact control, n=6 5.40±0.12 8.30±0.21 6.08±0.33
affected by potassium 

dichromate, n=6
3.96±
0.26*

2.97±
0.16*

6.55±
0.23*

3.96±
0.26*

2.97±
0.16*

6.55±
0.23*

affected by isoniazid  
and rifampicin, n=6

3.68±
0.20*

2.83±
0.11*

6.48±
0.27*

3.68±
0.20*

2.83±
0.11*

6.48±
0.27*

affected by potassium 
dichromate, isoniazid 
and rifampicin, n=6

3.18±
0.22*

2.42±
0.12*

5.78±
0.31*

3.18±
0.22*

2.42±
0.12*

5.78±
0.31*

Note: here and in the following tables * – significant differences between the animals of intact controls and the affected 
animals, р≤0.05.

N. I. burmas et al.



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compounds. ALT rate decreased till the end of 
the experiment by 58% (p≤0.05) in this group, 
when in the immature group – by 55%, in the 
mature one – by 45% in comparison with ani-
mals of the intact control.

In blood serum of the experimental animals, 
affected by K2Cr2O7, the AST rate was gradually 
increasing and reached the highest rate at the 
end of the experiment by 251% in the immature 
animals, by 181% – in the mature animals and 
267% – in the senior animals if compared to the 
control group of animals (Table 2). In the 
immature and mature rats AST rate increased 
in 3.0 and 2.1 times accordingly in comparison 
with the control group.

During the research the decrease in AST 
rate in liver of the affected animals of all age 
groups was determined (Table 2). In the imma-
ture animals the activity of this enzyme decre-
ased by 17% on the 7th day of the research after 
the administration of K2Cr2O7, in the ma ture 
animals – by 33% and in the senior ani mals – by 
39%. It was proved that the accumu lation of 
heavy metals, which got into the body of 
animals from the environment, took place in 
hepatocytes [11, 12].

We studied alkaline phosphatase rate in 
blood serum and liver of the affected rats 
(Table 3). It was established that this enzyme is 
a marker of liver disorder and indicates the 
inflammation in it.

The administration of potassium dichromate 
into the body of the immature animals caused 
the increase of alkaline phosphatase rate in 

blood serum in 1.3 times on the 7th day of the 
experiment, in the mature animals – in 1.5 times 
and in the senior animals – in 1.3 times, that 
caused toxic affection of liver. These changes 
were significant (р≤0.05).

We evidenced the highest rate of alkaline 
phosphatase in blood serum of the immature 
animals after combined effect of potassium 
dichromate, isoniazid and rifampicin, which was 
100% on the 7th day after affection and 127% – 
on the 14th day in comparison with the animals 
of the intact control.

In liver of the affected animals the ALP rate 
decreased during the experiment in all expe-
rimental groups (Table 3). The lowest rate of 
alkaline phosphatase was on the 14th day of the 
research in the mature animals after the 
combined effect of xenobiotics (772.86±29.62) 
nmol/(s·g) that is in 1.7 times lower than in the 
control group (1338.23±54.21 nmol/(s·g).

We evidenced a significant increase (р≤0.05) 
in total bilirubin content in blood serum of the 
animals of all age groups in comparison with 
control rats (Table 4). On the 14th day of the 
experiment the total bilirubin content increased 
by 53% in the immature animals, by 40% in the 
mature ones and by 28% in the senior rats after 
the affection with anti-TB drugs in comparison 
with the animals of the intact control.

We evidenced the highest content of total 
bilirubin at the end of the research in the 
mature animals after combined administration 
of K2Cr2O7, isoniazid and rifampicin, which was 
206% in comparison with intact animals that is 

Table 2. Aspartate aminotransferase rate in blood serum (mkmol/L·h) and liver (mkmol/kg·h) of 
rats affected by isoniazid, rifampicin and hexavalent chromium compounds, (M±m) 

Research 
material Group of animals

Age group of animals
immature mature senior

Research duration, days
7th 14th 7th 14th 7th 14th

blood 
serum

intact control, n=6 0.70±0.06 0.64±0.04 1.05±0.20
affected by potassium 

dichromate, n=6
0.94±
0.04*

1.76±
0.08*

0.93±
0.05*

1.16±
0.04*

2.04±
0.14*

2.80±
0.09*

affected by isoniazid and 
rifampicin, n=6

1.05±
0.05*

1.84±
0.10*

1.10±
0.05*

1.21±
0.06*

2.61±
0.09*

3.40±
0.14*

affected by potassium 
dichromate, isoniazid and 

rifampicin, n=6

1.21±
0.07*

2.07±
0.14*

1.19±
0.06*

1.34±
0.08*

3.22±
0.14*

3.85±
0.18*

liver intact control, n=6 1.21±0.11 2.66±0.06 2.48±0.12
affected by potassium 

dichromate, n=6
1.01±
0.05

0.91±
0.02*

1.79±
0.06*

1.44±
0.05*

1.52±
0.04*

1.25±
0.04*

affected by isoniazid and 
rifampicin, n=6

1.02±
0.04

0.86±
0.03*

1.66±
0.10*

1.34±
0.07*

1.45±
0.04*

1.18±
0.03*

affected by potassium 
dichromate, isoniazid and 

rifampicin, n=6

0.87±
0.03*

0.75±
0.04*

1.45±
0.10*

1.25±
0.06*

1.34±
0.04*

1.13±
0.04*

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by 13% and 20% higher than in the immature 
and senior animals, respectively.

The results of the research on the bile acids 
content in blood serum of the rats of all age 
groups are presented in table 5. In animals, 
which potassium dichromate was administrated 
to, the content of bile acids increased in all age 
groups (р≤0.05). On the 7th day of the research 
this rate increased by 35% in the immature 
animals, by 53% – in the mature animals and 
by 57% – in the senior animals if compared with 
the animals of the intact control. During the 
investigation of blood serum of the animals, 
which anti-TB drugs were administrated to, we 
evidenced a significant increase in bile acids 
content in the immature animals in 1.42 and 
1.71 times on the 7th and 14th days of the re-
search, respectively.

On the 7th day in the mature and the senior 
animals the bile acids content increased in 1.54 
and 1.76 times; on the 14th day – in 1.50 and 1.80 
times, respectively, in comparison with the 
animals of the intact control.

Discussion
It is established, that aminotransferases 

catalyze the reaction of transamination be-
tween the amino- and α-keto acids, take part 
in synthesis and forming of body proteins. The 
increasing activity of blood plasma enzymes, 
such as ALT and AST, demonstrates the level of 
hepatocytes damage and indicates liver disor-
ders. Due to this thesis, we studied aminotrans-
ferase rate in blood serum and liver of the rats 
of different age groups affected by xenobiotics. 
In the liver of the rats after combined adminis-

Table 3. Alkaline phosphatase rate in blood serum (nmol/s·L) and liver (nmol/s·g)  
of rats affected by isoniazid, rifampicin and hexavalent chromium compounds, (M±m) 

Research 
material Group of animals

Age group of animals
immature mature senior

Research duration, days
7th 14th 7th 14th 7th 14th

blood 
serum

intact control, n=6 1924.64±113.32 2405.80±159.13 3007.25±240.58
affected by potassium 

dichromate, n=6
2766.67±
159.13*

3518.48±
227.04*

3488.41±
206.60*

3849.28±
184.40*

3939.49±
205.29*

4360.51±
225.44*

affected by isoniazid 
and rifampicin, n=6

3247.83±
192.09*

3849.28±
206.60*

4210.15±
159.13*

4540.94±
142.96*

4330.43±
208.35*

4781.52±
137.81*

affected by potassium 
dichromate, isoniazid 
and rifampicin, n=6

3849.28±
159.13*

4360.51±
182.92*

4691.30±
104.17*

4751.45±
144.85*

4961.96±
137.81*

5352.90±
159.13*

liver intact control, n=6 739.78±30.90 1338.23±54.21 1705.11±74.21
affected by potassium 

dichromate, n=6
634.53±
20.53*

610.47±
14.30*

1004.42±
50.54*

878.12±
33.16*

1377.32±
41.84*

1305.14±
19.02*

affected by isoniazid 
and rifampicin, n=6

562.35±
19.44*

496.20±
20.17*

941.27±
38.82*

836.01±
35.68*

1341.23±
30.79*

1235.14±
16.64*

affected by potassium 
dichromate, isoniazid 
and rifampicin, n=6

514.24±
21.22*

457.10±
13.72*

878.12±
20.66*

772.86±
29.62*

1205.91±
26.93*

1106.67±
22.18*

Table 4. Total bilirubin content in blood serum (mkmol/L) of rats affected by isoniazid,  
rifampicin and hexavalent chromium compounds, (M±m) 

Group of animals

Age group of animals
immature mature senior

Research duration, days
7th 14th 7th 14th 7th 14th

intact control, n=6 12.19±0.55 12.49±0.47 15.09±0.78
affected by potassium 

dichromate, n=6
14.82±

0.98
17.97±
1.13*

14.10±
0.91

16.53±
1.17*

19.25±
1.27*

20.97±
1.61*

affected by isoniazid and 
rifampicin, n=6

13.38±
0.69

18.68±
1.50*

16.53±
1.17*

17.53±
1.61*

18.97±
1.12*

19.25±
1.27*

affected by potassium 
dichromate, isoniazid and 

rifampicin, n=6

16.97±
1.62*

23.53±
1.61*

23.10±
1.55*

25.67±
1.28*

23.82±
1.09*

28.08±
1.44*

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tration of toxicants we evidenced decrease in 
this enzyme rate, which indicated the cytolysis 
of hepatocytes and liver protein synthesis dys-
function in cases of affection by tuberculostat-
ics and hexavalent chromium compounds. It 
was determined that the increase in ALT rate 
in blood serum was higher than in liver. It could 
be caused by toxic influence of potassium di-
chromate with underlying isoniazid- rifampicin 
affection of liver. The damaged liver cannot 
synthesize this enzyme because of hepatocytes 
damage and their release in blood serum; so 
we evidenced increased rate of this enzyme. 

The determination of aminotransferase rate 
in blood serum is a sound indicator of the level 
of pathological process in liver. So we investi-
gated AST rate. AST rate in blood serum in-
creased and was the highest on the 14th day of 
the research (in 3.7 times higher than the nor-
mal range) in the senior animals affected by 
chrome-isoniazid-rifampicin. The decrease in 
AST rate in liver proved the transamination of 
aspartate according to breaking of the Citric 
acid cycle and negligible release of protein 
enzyme from tissue cells into blood. It was 
determined that increase in alkaline phos-
phatase rate in blood serum of the rats of all 
age groups after the administration of the in-
vestigated toxins into their bodies cause the 
release of ALP out of the damaged hepatocytes 
as well as the restoration of its synthesis in bile 
tubules. We consider that this dynamic activity 
of alkaline phosphatase may evidence the de-
velopment of hepatocytes destruction and in-
trahepatic cholestasis caused by liver architec-
tonics damage and possible development of 
cirrhosis.

It was established that hepatotoxicity of the 
metabolites of isoniazid and rifampicin caused 
the lipid peroxidation of hepatocyte biomem-
branes and bile formation dysfunction. Rifam-

picin can also inhibit the glucuronil-trans ami-
nases and cause bilirubin metabolism disorders 
and jaundice [10]. So, we had to examine total 
bilirubin content in blood serum of the animals 
affected by isoniazid, rifampicin and hexavalent 
chromium compounds. Increase in total biliru-
bin content under the influence of the toxicants 
evidenced the damage of cell membranes and 
erythrocytes predominantly and decrease in 
haemolysis as well as liver excretory dys-
function.

It was established, that in case of drug-
induced hepatitis the intestines and liver suffer 
from the affection, which was caused by the 
disorders of biosynthesis and hepatoenteral 
circulation of bile acids. After the combined 
administration of toxins (potassium dichromate, 
isoniazid and rifampicin) into the animals’ 
bodies we evidenced that the highest level of 
bile acids content in immature rats was at the 
end of the experiment, 239%, in comparison 
with the animals of the intact control. The 
increase in bile acids content in blood serum of 
the affected animals may have the toxic effect 
on hepatocyte mitochondria that caused incre-
ase in ions permeability to internal membrane 
of mitochondria, ions swelling and release of 
cytochrome C into cytosol as well as cells apo-
ptosis. The immature animals were the most 
sensitive to bile formation after administration 
of tuberculostatics and K2Cr2O7, although the 
increase in bile acids content was evidenced in 
the mature and senior animals.

Conclusions 
We determined the increase in aminotrans-

aminases and alkaline phosphatase rate in 
blood serum and their decrease in liver. It 
proved the toxic effect of hexavalent chromium 
compounds and tuberculostatics on the body 
of animals of all ages. It caused the disorder of 

Table 5. Bile acids content in blood serum (g/L) of rats affected by isoniazid,  
rifampicin and hexavalent chromium compounds, (M±m) 

Group of animals

Age group of animals
immature mature senior

Research duration, days 
7th 14th 7th 14th 7th 14th

intact control, n=6 6.95±0.43 9.48±0.58 12.02±0.64
affected by potassium  

dichromate, n=6
9.36±
0.68*

11.16±
0.62*

14.50±
0.50*

16.37±
0.67*

18.33±
0.98*

20.90±
0.95*

affected by isoniazid and 
rifampicin, n=6

9.90±
0.49*

11.89±
0.55*

14.60±
0.81*

16.69±
0.65*

18.09±
0.87*

21.59±
0.84*

affected by potassium  
dichromate, isoniazid and 

rifampicin, n=6

14.26±
0.55*

16.61±
0.43*

18.23±
0.75*

21.37±
0.87*

22.42±
0.81*

24.16±
0.95*

N. I. burmas et al.



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ISSN 2413-6077. IJMMR 2016 Vol. 2 Issue 1

hepatocyte plasmatic membranes permeability, 
which was evidenced by significant amount of 
enzymes in blood and caused liver inflammatory 
process in the affected animals. So, cholestasis 
developed. It was characterized by accumulation 
of bile acids and total bilirubin as well as other 

bile components in blood that could inhibit the 
synthesis of components complement in 
hepatocytes. The most pronounced metabolic 
disorders in cases of chrome-isoniazid-
rifampicin affection were evidenced in body of 
the animals of immature and senior age in 
comparison with mature animals.

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Received: 2015-12-28

N. I. burmas et al.