Effect of L-carnitine administered via subcutaneous injection on hematological parameters of laboratory animals

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Abstract

To date, there is no registered injectable dosage form of levocarnitine for veterinary use on the territory of the Russian Federation. Based on the above, the purpose of our work was to conduct preclinical studies of L-carnitine of subchronic toxicity for veterinary use in laboratory animals. Experiments to test the toxicity were performed on outbred rats in October 2021 at the vivarium of St. Petersburg State University of Veterinary Medicine. The study involved females weighing 190…210 grams, purchased from RAPPOLOVO Laboratory Animal Nursery. To study subchronic toxicity via subcutaneous injection, L-carnitine was administered in 2 dose levels. The doses were determined based on the results of the acute toxicity experiment: 1/5 and 1/10 of the maximum tolerated dose. The first experimental group (n=10) received the drug subcutaneously at a dose of 0.08 mg/kg (1/5 of 2000 mg/kg). The second experimental group (n = 10) received the drug subcutaneously at a dose of 0.04 mg/kg (1/10 of 2000 mg/kg). The control group (n = 10) received sodium chloride 0.09 % subcutaneously at a dose of 1/5 of 2000 mg/kg. The drug was administered subcutaneously daily for 42 days. Killing and blood sampling from the second half of the animals was carried out after assessing the recovery period (10 days after drug cancellation). As a result of studies of subchronic toxicity of subcutaneously administered L-carnitine for veterinary use in laboratory animals, it was found that the dosage of 1/5 of the maximum tolerated, and the dosage of 1/10 of the maximum tolerated, do not cause external signs of toxicosis and death of rats. No significant changes in the hematological parameters of blood of animals from the experimental and control groups were found.

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Table 1
Hematological blood parameters in experimental and control groups on the 43rd day of the experiment

Parameters

Group 1

Group 2

Control group

M ± SEM

M ± SEM

M ± SEM

Hematocrit, l/l

53.2 ± 1.6

52.6 ± 1.2

51.8 ± 2.0

Hemoglobin, g/l

121.8 ± 3.1

117.8 ± 3.5

117.0 ± 3.6

Leukocytes, 10·9/l

18.1 ± 1.3

18.0 ± 2.3

13.0 ± 1.6

Lymphocytes, %

67.8 ± 2.9

68.6 ± 3.2

61.8 ± 4.3

Monocytes, %

4.6 ± 0.9

4.0 ± 1.1

5.2 ± 0.6

Neutrophils Stab, %

2.4 ± 0.5

2.8 ± 0.6

2.4 ± 0.5

Neutrophils Segmented, %

24.6 ± 2.0

22.4 ± 3.0

25.4 ± 4.8

Prothrombin index, %

155.5 ± 6.9

160.2 ± 15.1

223.8 ± 14.4

ESR, mm/h

1.6 ± 0.4

1.2 ± 0.5

0.7 ± 0.1

Platelets, 10·9/l

153.0 ± 11.2

183.0 ± 25.3

159.4 ± 13.7

Eosinophils, %

0.4 ± 0.2

0.2 ± 0.2

1.0 ± 0.5

Erythrocytes, 10·12/l

7.5 ± 0.2

7.6 ± 0.2

7.6 ± 0.2

 

Table 2
Hematological blood parameters in experimental and control groups  on the 53rd day of the experiment

Parameters

Group 1

Group 2

Control group

M ± SEM

M ± SEM

M ± SEM

Hematocrit l/l

53.2 ± 1.1

50.6 ± 1.3

50.8 ± 1.1

Hemoglobin, g/l

121.6 ± 1.8

121.2 ± 1.6

112.6 ± 5.6

Leukocytes, 10·9/l

17.8 ± 1.6

15.6 ± 2.1

16.9 ± 2.5

Lymphocytes, %

66.6 ± 2.5

65.0 ± 1.3

71.2 ± 2.1

Mogocytes, %

1.8 ± 0.7

1.2 ± 0.2

3.4 ± 1.1

Neutrophils Stab, %

1.2 ± 0.4

1.0 ± 0.3

1.6 ± 0.5

Neutrophils Segmented, %

29.0 ± 3.5

22.4 ± 1.6

21.6 ± 2.4

Prothrombin index, %

132.7 ± 12.2

132.7 ± 2.8

135.3 ± 6.5

ESR, mm/h

0.1 ± 0.0

0.1 ± 0.0

0.1 ± 0.0

Platelets, 10·9/l

129.8 ± 10.7

169.6 ± 8.1

146.2 ± 6.5

Eosinophils, %

0.4 ± 0.2

0.4 ± 0.2

0.6 ± 0.2

Erythrocytes, 10·12/l

7.6 ± 0.3

7.5 ± 0.4

7.4 ± 0.4

×

About the authors

Lilia I. Sabirzyanova

St. Petersburg State University of Veterinary Medicine

Author for correspondence.
Email: l-sabirzyanova@list.ru
ORCID iD: 0000-0001-6516-8857

Assistant, Candidate of Veterinary Sciences

5 Chernigovskaya st., St. Petersburg, 196084, Russian Federation

Gella V. Konovalova

The Russian State Center for Animal Feed and Drug Standardization and Quality

Email: g.konovalova@vgnki.ru
ORCID iD: 0000-0001-5306-7303

Head of the Preclinical Research Department

5 Zvenigorodskoe highway, Moscow, 123022, Russian Federation

Valentina V. Tokar

The Russian State Center for Animal Feed and Drug Standardization and Quality

Email: v.tokar@vgnki.ru
ORCID iD: 0000-0001-9830-8799

Deputy Head, Preclinical Research Department

5 Zvenigorodskoe highway, Moscow, 123022, Russian Federation

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Copyright (c) 2023 Sabirzyanova L.I., Konovalova G.V., Tokar V.V.

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