Reduction of hepatotoxicity of nimesulide in mechanochemically obtained composition with disodium salt of glycyrrhizic acid
Nimesulide (NIM) is a nonsteroid anti-inflammatory drug which acts as a selective cyclooxygenase 2 inhibitor and is widely used for acute pain treatment. In medical practice, a large amount of data has been collected describing the effect of NIM on the body, while a hepatotoxic side effect of the dr...
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| Format: | Article |
| Language: | Russian |
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Russian Academy of Sciences, Siberian Branch Publishing House
2023-02-01
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| Series: | Сибирский научный медицинский журнал |
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| Online Access: | https://sibmed.elpub.ru/jour/article/view/969 |
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| author | E. S. Petrova N. A. Zhukova V. I. Evseenko M. V. Khvostov I. V. Meshkova T. G. Tolstikova A. V. Dushkin |
| author_facet | E. S. Petrova N. A. Zhukova V. I. Evseenko M. V. Khvostov I. V. Meshkova T. G. Tolstikova A. V. Dushkin |
| author_sort | E. S. Petrova |
| collection | DOAJ |
| description | Nimesulide (NIM) is a nonsteroid anti-inflammatory drug which acts as a selective cyclooxygenase 2 inhibitor and is widely used for acute pain treatment. In medical practice, a large amount of data has been collected describing the effect of NIM on the body, while a hepatotoxic side effect of the drug has been found. The exact mechanisms of such NIM-induced hepatotoxicity largely remain unknown but likely involve the intermediate reaction of its metabolism. Reduction of the hepatotoxic side effect of NIM is an actual problem for pharmacology. The aim of the present research was to evaluate the hepatotoxicity of the mechanochemically obtained composition of NIM with glycyrrhizic acid disodium salt (Na2GA) compared to pure NIM and a physical mixture of NIM with Na2GA. Material and methods. CD-1 mice were orally administered for 14 days: 1 group – mechanochemical composition NIM/Na2GA (1:10, m/m) at a dose of 1650 mg/kg; 2 group – physical mixture of NIM with Na2GA (1:10, m/m) at a dose of 1650 mg/kg; 3 group – pure NIM at a dose of 600 mg/kg (which pharmacokinetically corresponds to 1650 mg/kg of NIM/Na2GA); 4 group – vehicle (distilled water). The liver damage was assessed using histological studies and enzymatic activity of the alanine aminotransferase and aspartate aminotransferase in blood serum. Results. Histological analysis did not detect any changes in the liver of NIM/Na2GA-treated animals in comparison with a water-treated group. On the opposite, NIM given alone or as a physical mixture with Na2GA induced severe hepatotoxicity in experimental mice. Biochemical analysis of the blood serum revealed that mechanochemical NIM/Na2GA composition significantly reduced activity of the alanine aminotransferase (about 1.5 times) and aspartate aminotransferase (1.3 times) as compared with the pure NIM. Conclusions. The results obtained indicate a high potential for the practical application of the NIM/Na2GA mechanochemical composition. |
| first_indexed | 2024-03-08T14:32:43Z |
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| id | doaj.art-2b4f13bf0d18412a921657989e668f96 |
| institution | Directory Open Access Journal |
| issn | 2410-2512 2410-2520 |
| language | Russian |
| last_indexed | 2025-03-14T13:18:36Z |
| publishDate | 2023-02-01 |
| publisher | Russian Academy of Sciences, Siberian Branch Publishing House |
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| series | Сибирский научный медицинский журнал |
| spelling | doaj.art-2b4f13bf0d18412a921657989e668f962025-02-28T13:43:58ZrusRussian Academy of Sciences, Siberian Branch Publishing HouseСибирский научный медицинский журнал2410-25122410-25202023-02-01431717810.18699/SSMJ20230107479Reduction of hepatotoxicity of nimesulide in mechanochemically obtained composition with disodium salt of glycyrrhizic acidE. S. Petrova0N. A. Zhukova1V. I. Evseenko2M. V. Khvostov3I. V. Meshkova4T. G. Tolstikova5A. V. Dushkin6Institute of Solid State Chemistry and Mechanochemistry SB RASN.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RASInstitute of Solid State Chemistry and Mechanochemistry SB RASInstitute of Solid State Chemistry and Mechanochemistry SB RAS; N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RASN.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RASN.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RASInstitute of Solid State Chemistry and Mechanochemistry SB RASNimesulide (NIM) is a nonsteroid anti-inflammatory drug which acts as a selective cyclooxygenase 2 inhibitor and is widely used for acute pain treatment. In medical practice, a large amount of data has been collected describing the effect of NIM on the body, while a hepatotoxic side effect of the drug has been found. The exact mechanisms of such NIM-induced hepatotoxicity largely remain unknown but likely involve the intermediate reaction of its metabolism. Reduction of the hepatotoxic side effect of NIM is an actual problem for pharmacology. The aim of the present research was to evaluate the hepatotoxicity of the mechanochemically obtained composition of NIM with glycyrrhizic acid disodium salt (Na2GA) compared to pure NIM and a physical mixture of NIM with Na2GA. Material and methods. CD-1 mice were orally administered for 14 days: 1 group – mechanochemical composition NIM/Na2GA (1:10, m/m) at a dose of 1650 mg/kg; 2 group – physical mixture of NIM with Na2GA (1:10, m/m) at a dose of 1650 mg/kg; 3 group – pure NIM at a dose of 600 mg/kg (which pharmacokinetically corresponds to 1650 mg/kg of NIM/Na2GA); 4 group – vehicle (distilled water). The liver damage was assessed using histological studies and enzymatic activity of the alanine aminotransferase and aspartate aminotransferase in blood serum. Results. Histological analysis did not detect any changes in the liver of NIM/Na2GA-treated animals in comparison with a water-treated group. On the opposite, NIM given alone or as a physical mixture with Na2GA induced severe hepatotoxicity in experimental mice. Biochemical analysis of the blood serum revealed that mechanochemical NIM/Na2GA composition significantly reduced activity of the alanine aminotransferase (about 1.5 times) and aspartate aminotransferase (1.3 times) as compared with the pure NIM. Conclusions. The results obtained indicate a high potential for the practical application of the NIM/Na2GA mechanochemical composition.https://sibmed.elpub.ru/jour/article/view/969nimesulidehepatotoxicitysolid pharmaceutical dispersionsdisodium salt of glycyrrhizic acid |
| spellingShingle | E. S. Petrova N. A. Zhukova V. I. Evseenko M. V. Khvostov I. V. Meshkova T. G. Tolstikova A. V. Dushkin Reduction of hepatotoxicity of nimesulide in mechanochemically obtained composition with disodium salt of glycyrrhizic acid Сибирский научный медицинский журнал nimesulide hepatotoxicity solid pharmaceutical dispersions disodium salt of glycyrrhizic acid |
| title | Reduction of hepatotoxicity of nimesulide in mechanochemically obtained composition with disodium salt of glycyrrhizic acid |
| title_full | Reduction of hepatotoxicity of nimesulide in mechanochemically obtained composition with disodium salt of glycyrrhizic acid |
| title_fullStr | Reduction of hepatotoxicity of nimesulide in mechanochemically obtained composition with disodium salt of glycyrrhizic acid |
| title_full_unstemmed | Reduction of hepatotoxicity of nimesulide in mechanochemically obtained composition with disodium salt of glycyrrhizic acid |
| title_short | Reduction of hepatotoxicity of nimesulide in mechanochemically obtained composition with disodium salt of glycyrrhizic acid |
| title_sort | reduction of hepatotoxicity of nimesulide in mechanochemically obtained composition with disodium salt of glycyrrhizic acid |
| topic | nimesulide hepatotoxicity solid pharmaceutical dispersions disodium salt of glycyrrhizic acid |
| url | https://sibmed.elpub.ru/jour/article/view/969 |
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