ANALYSIS OF KK1 COMPOUND EFFECTS ON IMMUNOLOGICAL AND BIOCHEMICAL PARAMETERS IN PRENATALLY TOBACCO-EXPOSED RAT WISTAR OFFSPRING



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Abstract

Abstract

One of the widespread low-toxicity factors affecting animals and humans is active and passive tobacco smoking. In previous studies, the authors investigated morphological and immunological parameters in passively smoke-exposed rats.

Objective This study continues research in this direction and focuses on analyzing the effects of the synthetic peptide KK1, a structural analogue of the primary sequence of ACTH (15-18) (Acetyl-(D-Lys)-Lys-Arg-Arg-amide) with antioxidant and stress-protective properties on the phagocytic activity of peritoneal macrophages and the intensity of free radical oxidation in the liver and serum.

Materials and Methods Immunological and biochemical parameters were assessed in 60 offspring of smoke-exposed and non-exposed Wistar rats. Pregnant rats were subjected to tobacco smoke (8 hours a day, from 1st to 20th day of gestation). Control groups received saline, while experimental groups were administered KK1 intranasally (at a dose of 40 μg/kg, intranasally, five times every other day over a 10-day period). At 21 days postpartum, offspring were evaluated for phagocytic indices, circulating immune complex levels (CIC), hepatic enzyme activity (alanine aminotransferase (ALT), aspartate aminotransferase (AST)), oxidative stress markers (malondialdehyde (MDA), diene conjugates (DC)), and antioxidant enzymes (superoxide dismutase (SOD), catalase).

Results The study demonstrated that prenatal tobacco smoke exposure in rat offspring resulted reduced phagocytic activity, but elevated neutrophil metabolic activity, increased serum AST activity, activated free radical oxidation (elevated MDA, DC) with suppression of endogenous antioxidant defense mechanisms (decreased SOD and catalase). Administration of the KK1 compound normalized phagocytic indices, reduced AST activity and restored antioxidant defenses. These findings support the antioxidant properties of KK1 under passive smoking conditions, highlighting its immunoprotective effects. The mechanism of action of the KK1 compound may be associated with modulation of synaptic membrane fluidity, regulation of receptor functions, protein phosphorylation processes, and suppression of excessive cytokine synthesis. The observed reduction in free radical oxidation products and enhancement of catalase activity align with existing evidence of KK1’s antioxidant and stress-protective efficacy.

Conclusions The KK1 compound demonstrates antioxidant and immunoprotective effects by mitigating the adverse consequences of prenatal tobacco smoke exposure in rat offspring. These findings support its potential application in studies investigating the impact of low-toxicity environmental factors on experimental animal models.

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Таблица 2.

Содержание МДА (нмоль/мг белка) и ДК (ед.опт.пл./мг белка) в печени и сыворотке крови, активность антиоксидантных ферментов в эритроцитах крыс, Mе (Q₁–Q₃)

Table 2

Content of MDA (nmol/mg protein) and DC (OD units/mg protein) in the liver and serum, activity of antioxidant enzymes in rat erythrocytes, Median (Q₁–Q₃)

 

Показатели

1 группа

Group 1

(n=12)

2 группа

Group 2

(n=12)

3 группа

Group 3

(n=12)

4 группа

Group 4

 (n=12)

Печень

Liver

МДА

MDA

0,89 (0,81-0,95)

1,13 (0,80-1,23)

0,92 (0,86-1,03)

0,94 (0,84-1,01)

ДК

DC

0,20

(0,16-0,24)

0,37* (0,34-0,41)

0,19 (0,14-0,21)

0,36* (0,33-0,37)

Сыворотка крови

Serum

МДА

MDA

8,9 (8,3-10,9)

10,5* (9,0-13,2)

8,72 (7,98-10,62)

8,95 (8,26-9,94)

ДК

DC

0,21 (0,18-0,26)

0,25 (0,15-0,38)

0,17 (0,16-0,25)

0,19 (0,17-0,24)

Эритроциты

Erythrocytes

Каталаза, усл.ед./гHb

Catalase, conv. units/g Hb

268,0 (215,2-354,9)

185,7 (168,7-231,1)

217,8 (198,7-281,1)

216,6 (185,6-262,4)

СОД, усл.ед./гHb

SOD, conv. units/g Hb

227 (178,5-273,5)

165 (141,2-241,1)

172,8 (159,3-183,3)

169,3 (167,5-175,4)

* - статистически значимые различия (p < 0,05) с показателями 1 контрольной группы

* Significant differences (p<0.05) from the control group 1

×

About the authors

Natalia A. Kuzmicheva

Orenburg State Medical University, Orenburg, Russian Federation

Email: natalie-vip@list.ru
ORCID iD: 0000-0003-4144-1470
SPIN-code: 1218-2666
Scopus Author ID: 57291132800

Senior Lecturer, Department of Pharmaceutical Chemistry

Russian Federation, 6 Sovetskaya St., Orenburg, 460000

Aleksandr I. Smolyagin

Orenburg State Medical University, Orenburg, Russian Federation

Email: a.i.smolyagin@mail.ru
ORCID iD: 0000-0001-5573-6646

PhD, MD (Medicine), Professor, Department of Clinical Laboratory Diagnostics

Russian Federation, 6 Sovetskaya St., Orenburg, 460000

Julia V. Filippova

Orenburg State Medical University, Orenburg, Russian Federation

Author for correspondence.
Email: yuliaf78@mail.ru

PhD (Medicine), Associate Professor, Department of Pharmaceutical Chemistry

Russian Federation, 6 Sovetskaya St., Orenburg, 460000

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