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 selective cyclooxygenase 2 inhibitor and widely used for acute pain treatment. In medical practice, large amount of data has been collected describing the effect NIM on body, while hepatotoxic side found. The exact mechanisms such NIM-induced hepatotoxicity largely remain unknown but likely involve intermediate reaction its metabolism. Reduction an actual problem pharmacology. aim present research was to evaluate mechanochemically obtained composition with glycyrrhizic acid disodium salt (Na GA) compared pure physical mixture Na GA. Material methods. CD-1 mice were orally administered 14 days: 1 group – mechanochemical NIM/Na GA (1:10, m/m) at dose 1650 mg/kg; Na2GA 3 600 mg/kg (which pharmacokinetically corresponds GA); 4 vehicle (distilled water). liver damage assessed using histological studies enzymatic activity alanine aminotransferase aspartate in blood serum. Results. Histological analysis did not detect any changes GA-treated animals comparison water-treated group. On opposite, given alone or induced severe experimental mice. Biochemical serum revealed that significantly reduced (about 1.5 times) (1.3 NIM. Conclusions. results indicate high potential practical application composition.