Toxicity Study of Pharmacological Pair Encapsulated Citrobacter freundii C115H Methionine γ-Lyase / Methiin

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Рұқсат жабық Тек жазылушылар үшін

Аннотация

The acute and subchronic toxicity of the pharmacological pair based on encapsulated Citrobacter freundii C115H methionine γ-lyase enzyme/prodrug (methiin) was studied in female ICR mice. The drug showed a weak/moderate dose-dependent hepatotoxic effect. Most of the identified changes in liver morphology were insignificant or mild deviations from the norm. Long-term use of a single therapeutic dose per mouse of 1.5 U C. freundii C115H methionine γ-lyase @ (PEG−P(Asp)70/PLL70)-PICsome / 2 mg methiin led to a slight decrease in the weight of animals without obvious signs of intoxication. A quarter of the animals in this group had no deviations from the norm in liver morphology. No nephrotoxic effect in all study groups was found.

Толық мәтін

Рұқсат жабық

Авторлар туралы

S. Revtovich

Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences

Хат алмасуға жауапты Автор.
Email: svetla21@mail.ru
Ресей, Moscow, 119991

V. Kulikova

Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences

Email: svetla21@mail.ru
Ресей, Moscow, 119991

V. Koval

Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences

Email: svetla21@mail.ru
Ресей, Moscow, 119991

A. Lyfenko

Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences

Email: svetla21@mail.ru
Ресей, Moscow, 119991

V. Kazakov

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences

Email: svetla21@mail.ru
Ресей, Pushchino, Moscow Region, 142290

A. Chernov

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences

Email: svetla21@mail.ru
Ресей, Pushchino, Moscow Region, 142290

G. Telegin

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences

Email: svetla21@mail.ru
Ресей, Pushchino, Moscow Region, 142290

A. Zemskaya

Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences

Email: svetla21@mail.ru
Ресей, Moscow, 119991

N. Anufrieva

Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences

Email: svetla21@mail.ru
Ресей, Moscow, 119991

E. Morozova

Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences

Email: svetla21@mail.ru
Ресей, Moscow, 119991

P. Solyev

Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences

Email: svetla21@mail.ru
Ресей, Moscow, 119991

Әдебиет тізімі

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2. Appendix
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3. Fig. 1. Principle of action of the pharmacological pair encapsulated MGL/methionine.

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4. Fig. 2. Liver fragments of female mice of the control group. Haematoxylin and eosin staining. The arrows indicate: a - small foci of mononuclear infiltration in the parenchyma of one of the lobes of the organ (mouse 5.1); b - hypertrophy of individual hepatocytes (mouse 5.2).

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5. Fig. 3. Liver fragments of female mice on day 7 after a single injection of 1.5 U C115H-PIC-som MGL/2 mg methiin. Haematoxylin and eosin staining. The arrows indicate: a - small foci of mononuclear infiltration in the parenchyma of one of the organ lobes (mouse 1.2); b - hepatocyte karyomegaly (mouse 1.3).

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6. Fig. 4. Fragments of the liver of female mice on day 7 after a single administration of 1.5 units of C115H-PIC-com MGL / 10 mg of methiine. Staining with hematoxylin and eosin. The arrows indicate: a – small foci of infiltration by segmented leukocytes (mouse 2.1), b – foci of mononuclear infiltration with single segmented leukocytes and phagocytosis of dead hepatocytes (mouse 2.6).

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7. Fig. 5. Fragments of the liver of female mice on day 7 after a single administration of 1.5 units of C115H-PIC-com MG/20 mg of methiine. Staining with hematoxylin and eosin. The arrows indicate: a – the focus of hepatocytes with initial necrosis (mouse 3.4), b – hepatocytes with pigmented inclusions in the cytoplasm (mouse 3.5).

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8. Fig. 6. Fragments of the cortical (a) and cerebral (b) substances of the kidney of a female mouse of the control group (mouse 5.1). The usual histological structure of the organ. Staining with hematoxylin and eosin.

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9. Fig. 7. Fragments of the renal cortex of female mice on day 7 after a single administration of 1.5 units of C115H-PIC-com MG/2 mg of methiine. Staining with hematoxylin and eosin. The arrows indicate: a – the phenomena of chronic progressive nephropathy (mouse 1.5), b – a tubular cyst (solid arrow) lined with flattened epithelium (dotted arrows; mouse 1.3).

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10. Fig. 8. Fragments of the renal cortex of a mouse (3.5 mouse) on day 7 after a single administration of 1.5 units of C115H-PIC-com MG/20 mg of methiine. Staining with hematoxylin and eosin. The arrows indicate the phenomena of chronic progressive nephropathy (a) and perivascular focus of mononuclear infiltration (b).

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11. Fig. 9. Fragments of the liver of female mice of the control group. Staining with hematoxylin and eosin. a – The arrows indicate the focus of mononuclear infiltration with segmented leukocytes (mouse 5.4). b – The usual histological structure of the organ (mouse 5.3).

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12. Fig. 10. Fragments of the liver of female mice on day 15 after 7-fold administration of 1.5 units of C115H-PIC-com MG/2 mg of methiine. Staining with hematoxylin and eosin. The arrows indicate: a – a focus of hepatocytes with initial necrosis (mouse 4.1); b – hepatocytes with pigmented inclusions in the cytoplasm (mouse 4.3); c – small foci of extramedullary hematopoiesis (mouse 4.6); d – the usual histological structure of the organ (mouse 4.7).

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13. Fig. 11. Fragments of the cortical (a) and cerebral (b) substances of the mouse kidney on day 15 after 7-fold administration of 1.5 units of C115H-PIC-com MG/2 mg of methiine (mouse 4.4). The usual histological structure of the organ. Staining with hematoxylin and eosin.

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