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American Journal Of Biomedical Science & Pharmaceutical Innovation    
(ISSN – 2771-2753) 
VOLUME 03 ISSUE 12 PAGES: 48-55 

SJIF IMPACT FACTOR (2021: 5. 705) (2022: 5. 705) (2023: 6.534) 
OCLC – 1121105677     

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Publisher: Oscar Publishing Services 

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ABSTRACT 

The results showed that immunomodulin has a moderate regulatory effect on the spontaneous blast transformation 

of lymphocytes in the in vitro system. The costimulatory effect of immunomodulin in the reaction of PHA-induced 

blast transformation of T-lymphocytes was revealed. The data we obtained on the rather pronounced interferon-

inducing properties of Sanogen developed by us and its combinations with well-known inductors - Cycloferon and 

Betaleukin, can be of practical use in the treatment of infectious pathology, especially viral hepatitis, when the 

combination of hepatoprotective, anti-inflammatory, antiviral, immunomodulatory and detoxification mechanisms of 

action, in the absence of toxicity and side effects, will ensure the development of sanogenetic processes in the 

patient's body. 

KEYWORDS 

Toxicity, side effects, treatment of cancer, cells. 

INTRODUCTION

  Research Article 

 

INFLUENCE OF MODIFIED PEPTIDES FROM THE FETAL THYMUS ON THE 

ACTIVITY OF T-LYMPHOCYTES AND NATURAL KILLERS IN 

EXPERIMENTAL VIRAL HEPATITIS  
 

Submission Date: December 15, 2023, Accepted Date:  December 20, 2023,  

Published Date: December 25, 2023  

Crossref doi: https://doi.org/10.37547/ajbspi/Volume03Issue12-09 

 

 

Bolta A. Kahorov  
National University of Uzbekistan named after Mirzo Ulugbek, University str., 4, 100174, Tashkent, Uzbekistan 

 

Sevara L. Rasulova  
National University of Uzbekistan named after Mirzo Ulugbek, University str., 4, 100174, Tashkent, Uzbekistan 

 

Journal Website: 

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com/index.php/ajbspi 

Copyright: Original 

content from this work 

may be used under the 

terms of the creative 

commons attributes 

4.0 licence. 

 

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Volume 03 Issue 12-2023 49 

                 

 
 

   
  
 

American Journal Of Biomedical Science & Pharmaceutical Innovation    
(ISSN – 2771-2753) 
VOLUME 03 ISSUE 12 PAGES: 48-55 

SJIF IMPACT FACTOR (2021: 5. 705) (2022: 5. 705) (2023: 6.534) 
OCLC – 1121105677     

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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Thymus extracts, incl. thymosin is used in the 

treatment of cancer, autoimmune diseases, many 

chronic infectious processes, etc. [1,2,10, 28, 37]. The 

most important mechanism of action of thymic 

peptides is the enhancement of the functional activity 

of T-lymphocytes, however, the multi-stage process of 

developing an immune response includes the 

activation of not only cellular but also humoral 

immunity factors, contributing to an increase in the 

production of specific antibodies, cytokines, 

inflammatory factors, etc. [7, 16, 22 ]. Natural immunity 

is largely determined by killer cells (NK), which play a 

decisive protective role in the early stages of viral 

aggression [26]. Among the known thymic peptides, a 

drug obtained from fetal sheep thymus is particularly 

interesting. It consists of 15 peptides. Its 

immunocorrective effect was shown in experiments 

and clinical observations, in connection with which it 

received the name "Immunomodulin". It is mass-

produced in the state of emergency "Immunomed" 

(Tashkent) and approved for medical use in Uzbekistan 

and Kazakhstan [2].  

To increase the immunobiological activity of thymic 

peptides, we attempted to combine them with metal 

ions, as is the case in thymulin, which circulates in the 

bloodstream as a nanopeptide combined with zinc. 

The aim of the work is to study the effect of zinc-

modified thymus peptides on the functional activity of 

T-lymphocytes and human natural killer cells in the in 

vitro system and to evaluate the effectiveness of 

interferonogenesis and antiviral action under the 

influence of Sanogen, Betaleukin, Cycloferon and their 

combinations in the experiment.  

 

METHODS 

Determination of the effect of drugs on the 

proliferative response of T-lymphocytes. The material 

for the study of lymphocyte blastogenesis was 

peripheral blood mononuclear cells of 32 patients with 

chronic viral hepatitis B aged 20-49 years. 

Phytohemagglutinin (PHA) (Sigma) and concanavalin A 

(Con A) (Pharmacia) at suboptimal concentrations (10 

µg/mL) were used as RBTL activators. Modified and 

unmodified peptides were added to the lymphocytes 

(1 million/ml) at a final concentration of 0.01 μg/ml in 

the test samples. The tablet was incubated at 37ºC for 

1 hour, after which the corresponding mitogen was 

added to the wells. Only mitogen was added to control 

lymphocyte samples. Mitogen was not used in the 

study of spontaneous blast transformation of 

lymphocytes. After 48 hours, 3H-thymidine was added 

to the samples at a concentration of 1 μCi/ml. The 

results of the reaction were taken into account 72 

hours after the start of cultivation.  

To quantify the effect of immunomodulin on the 

proliferative response of T-lymphocytes, the impact 

index (IV) was used, which was calculated by the 

formula: 

IV = (Iо – Ik)/Ik • 100%, 

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Volume 03 Issue 12-2023 50 

                 

 
 

   
  
 

American Journal Of Biomedical Science & Pharmaceutical Innovation    
(ISSN – 2771-2753) 
VOLUME 03 ISSUE 12 PAGES: 48-55 

SJIF IMPACT FACTOR (2021: 5. 705) (2022: 5. 705) (2023: 6.534) 
OCLC – 1121105677     

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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where: Io - the number of pulses per minute (imp/min) 

in the experiment; 

Ik - the number of pulses/min in the control. 

 

RESULTS AND DISCUSSION 

It was found that the average value of spontaneous 

RBTL in patients with hepatitis in control group 1 

(without incubation with mitogen and 

immunomodulin) was 280±14 imp/min with a range of 

individual fluctuations from 153 to 404 imp/min (Fig. 1). 

In the presence of immunomodulin (control 2), the 

indicators of spontaneous blastogenesis significantly 

increased on average in the group up to 351 ± 26 

imp/min with a range of individual fluctuations from 

207 to 673 imp/min. The index of drug effect on 

spontaneous RBTL was +25.3% (P<0.05). The 

introduction of the zinc-modified peptide into the 

culture increased the rates of spontaneous 

transformation of T-lymphocytes to an average of 

415±36 pulses/min. With a range of individual 

fluctuations from 248 to 650 imp/min. The index of 

drug effect on spontaneous RBTL was +48% (P<0.05 

with control 2 and P<0.001 with control 1). 

We also studied the functional activity of T-

lymphocytes in terms of their ability to enter the 

mitotic cycle under the influence of PHA. It was 

established that under the influence of lectin, the blast 

transformation of lymphocytes in general in the 

control group 1 is (51.4±3.3) x 103 imp/min with 

individual fluctuations in indicators from 41 to 74 

thousand imp/min. 

In control group 2, the mean value of this indicator did 

not differ significantly from control 1 and amounted to 

57.0 ± 2.4 thousand imp/min with individual values from 

42 to 77 thousand imp/min. The impact index of 

immunomodulin on average for the group was +11%. 

In the main group, the average value of this indicator 

significantly differed from control 1 and control 2 and 

amounted to 65.0 ± 2.4 thousand imp/min with 

individual values from 48 to 86 thousand imp/min. The 

impact index of modified immunomodulin averaged 

+27% per group (P<0.05 with control 2 and P<0.001 with 

control 1).  

In the experiment with pre-treatment with the drug 

only mononuclear cells, similar results were obtained. 

Thus, the incubation of effector cells with 

immunomodulin (without target cells) showed a 

significant stimulation of the membrane toxic activity 

of natural killer cells in all studied groups. In this group 

of experiments, 2 controls were used: preliminary 

parallel incubation of effector cells only in a nutrient 

medium (control 1) and with a peptide (control 2). In 

the experimental group, the metallopeptide was 

evaluated. Thus, in healthy donors, the EC cytotoxicity 

index was 51.2±1.9%; incubation with the modified 

peptide increases these values to 65.7±1.6%; 

preincubation with immunomodulin activates them up 

to 58.3±1.7%. The difference between the experimental 

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(ISSN – 2771-2753) 
VOLUME 03 ISSUE 12 PAGES: 48-55 

SJIF IMPACT FACTOR (2021: 5. 705) (2022: 5. 705) (2023: 6.534) 
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values and controls was significant (P<0.05 with 

control 2 and P<0.001 with control 1). 

Quantitative assessment of the induction of 1PM by 

Sanogen, Betaleukin and Cycloferon with separate and 

combined administration to experimental animals. 

It has been established that Betaleukin induces IFN 

production within 96 hours (observation period); the 

maximum titer was noted after 12 hours and reached 

512 units. The average titer was 118±16 units. (Fig.1, 3). 

Sanogen also had quite pronounced interferonogenic 

properties - the maximum titer was 128 units. after 24 

hours with an average value of 47 ± 4 units (Fig. 1, 3). 

When using monopreparations, Cycloferon was the 

most effective - the maximum IFN was 1024 units. after 

48 hours. Under his influence, the average titer during 

a 120-hour observation was 295 ± 35 units. (fig.3) 

 

 
 

Fig.1. Dynamics of serum interferon activity in mice after a single separate intraperitoneal injection of Sanogen (C), 

Betaleukin (B) and Cycloferon (Cy) in effective doses: 2 μg/kg; 10 ng/kg and 4 µg/kg, respectively. 

 

The introduction of Betaleukin with Cycloferon sharply 

increased the activity of serum IFN to an average of 

1060 ± 80 units. The expected increase was to be 395 

units. (100 units of Betaleukin + 295 units of 

Cycloferon), i.e. it turned out to be 2.7 times higher 

than the additive value. Synergy was also manifested in 

the accumulation of the maximum titer up to 2048 

units, which is 1.3 times higher than expected (512 units 

+ 1024 units = 1536 units). There was also a shift in the 

peak of IFN production for a period of 48 hours. Even 

4 hours after the combined administration of inducers, 

the IFN activity was high and amounted to 256 units, 

while the serum activity remained significant and after 

120 hours was 512 units. The synergistic effect for this 

period was 32 times higher than the additive one. 

0

200

400

600

800

1000

1200

4 12 24 48 72 96 120

Activity titer IFN, units

B C Cy

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Volume 03 Issue 12-2023 52 

                 

 
 

   
  
 

American Journal Of Biomedical Science & Pharmaceutical Innovation    
(ISSN – 2771-2753) 
VOLUME 03 ISSUE 12 PAGES: 48-55 

SJIF IMPACT FACTOR (2021: 5. 705) (2022: 5. 705) (2023: 6.534) 
OCLC – 1121105677     

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Publisher: Oscar Publishing Services 

Servi 

The simultaneous administration of Sanogen and 

Cycloferon sharply increased the activity of serum IFN 

to an average of 805 ± 75 units, since the expected 

average increase was to be 323 units. (28 Sanogen units 

+ 295 Cycloferon units), it turned out to be 2.5 times 

higher than the additive value (Fig. 3). Synergy also 

manifested itself in the accumulation of the maximum 

IFN titer up to 2048 units, which is 1.8 times higher than 

expected (128 units + 1024 units). The peak of IFN 

production was recorded for a period of 48 hours, 

which corresponded to the period of maximum serum 

activity with the introduction of Cycloferon. It should 

be noted that already 4 hours after the combined 

administration of these inducers, the IFN activity was 

the highest - 256 units. (Fig. 2). Despite the early and 

very pronounced induction, serum activity remained 

significant throughout the entire observation period, 

and even after 120 hours it was 256 units. (Fig. 2), 

whereas with the separate administration of Sanogen 

or Cycloferon, the titers were only 2 units each. and 16 

units. (Fig. 1), i.e. the synergistic effect was 14 times 

higher than the additive one. 

Therefore, with the simultaneous administration of 

Sanogen and Cycloferon, a pronounced synergism was 

found in the induction of endogenous IFN, since IFN 

synthesis was noted, the high activity of which is 

recorded in the circulating blood from 4 to 120 hours 

with a maximum of 2048 units 48 hours after injection, 

1.8 times higher than additive action when used 

separately. 

To quantify the activity of interferonogenesis under 

the influence of monodrugs and their combinations, 

we calculated the average values for the duration of 

the study for 5 days for each option (Fig. 3). It has been 

established that Cycloferon (295±36 units) is the most 

active among monopreparations. All used 

combinations of drugs were more powerful 

interferonogens compared to it. Under the influence of 

Sanogen with Betaleukin, the average activity of 

interferonogenesis was 457±45 units, Sanogen with 

Cycloferon - 805±56 units, and Betaleukin with 

Cycloferon -1060±52 units. 

 

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Volume 03 Issue 12-2023 53 

                 

 
 

   
  
 

American Journal Of Biomedical Science & Pharmaceutical Innovation    
(ISSN – 2771-2753) 
VOLUME 03 ISSUE 12 PAGES: 48-55 

SJIF IMPACT FACTOR (2021: 5. 705) (2022: 5. 705) (2023: 6.534) 
OCLC – 1121105677     

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Publisher: Oscar Publishing Services 

Servi 

 
Fig. 3. Average values of serum interferon titers for 5 days after separate and combined 

administration of Sanogen (C), Betaleukin (B), and Cycloferon (Cy) to mice. 

 

CONCLUSIONS 

The fundamental feature of the action of fetal thymus 

peptides is the dependence of the severity and 

direction of their effects on the initial state of 

regulated cells, which contributes to the normalization 

of processes that are out of balance. 

-thymic peptides combined with zinc have a regulatory 

effect on the proliferative activity of T-lymphocytes 

through the interaction of their cell receptors with 

mitogen and thymus peptides, which ultimately leads 

to a cascade synthesis of cytokines, which in turn 

modulates the proliferation of T-cells and cytotoxic 

activity of natural killers. 

- pronounced interferon-inducing properties of 

Sanogen developed by us and its combinations with 

well-known inductors - Cycloferon and Betaleukin, can 

have practical application in the treatment of 

infectious pathology, especially viral hepatitis, when 

the combination of hepatoprotective, anti-

inflammatory, antiviral, immunomodulatory and 

detoxification mechanisms of action 

 

REFERENCES 

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Volume 03 Issue 12-2023 54 

                 

 
 

   
  
 

American Journal Of Biomedical Science & Pharmaceutical Innovation    
(ISSN – 2771-2753) 
VOLUME 03 ISSUE 12 PAGES: 48-55 

SJIF IMPACT FACTOR (2021: 5. 705) (2022: 5. 705) (2023: 6.534) 
OCLC – 1121105677     

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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American Journal Of Biomedical Science & Pharmaceutical Innovation    
(ISSN – 2771-2753) 
VOLUME 03 ISSUE 12 PAGES: 48-55 

SJIF IMPACT FACTOR (2021: 5. 705) (2022: 5. 705) (2023: 6.534) 
OCLC – 1121105677     

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Publisher: Oscar Publishing Services 

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