Phosphatidylinositol 3-kinase gamma participates in nimesulide-induced hepatic damage
| Autor: | Anna Sofia Miranda Loiola Araújo, Álvaro Xavier Franco, Even Herlany Pereira Alves, Cynthia Maria Carvalho Pereira, José Victor do Nascimento Lima, Daniel Fernando Pereira Vasconcelos, Joveline Costa de Oliveira, Francisca Géssica Oliveira Silva, Sarah Izabelly Alves Lemos, Lauanda da Rocha Rodrigues, Pedro Marcos Gomes Soares, Marcelo de Carvalho Filgueiras, Jayro dos Santos Ferreira, Genilson José Dias Júnior, Tarcisio Vieira de Brito, André Luiz dos Reis Barbosa, Carlos Eduardo da Silva Monteiro, Jefferson Soares de Oliveira |
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| Rok vydání: | 2021 |
| Předmět: |
Pharmaceutical Science
Inflammation Pharmacology medicine.disease_cause Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Quinoxalines medicine Animals Cyclooxygenase Inhibitors Dimethyl Sulfoxide Phosphatidylinositol Phosphoinositide-3 Kinase Inhibitors 030304 developmental biology Sulfonamides 0303 health sciences biology Kinase NF-kappa B Free Radical Scavengers Oxidative Stress Treatment Outcome chemistry 030220 oncology & carcinogenesis biology.protein Thiazolidinediones Cyclooxygenase Liver function Chemical and Drug Induced Liver Injury Phosphatidylinositol 3-Kinase medicine.symptom Immunostaining Oxidative stress Nimesulide medicine.drug |
| Zdroj: | Journal of Pharmacy and Pharmacology. 73:496-504 |
| ISSN: | 2042-7158 0022-3573 |
| DOI: | 10.1093/jpp/rgaa049 |
| Popis: | Objective To evaluate the participation of the phosphatidylinositol 3-kinase pathway in the liver damage caused by nimesulide. Methods Liver damage been induced by nimesulide. Mice were treated with either 2% dimethyl sulfoxide or AS605240, a phosphatidylinositol 3-kinase gamma pathway antagonist. Blood samples were collected for function assays of liver. The liver was removed for analysis of liver weight/animal weight ratio, histopathological parameters, oxidative and nitrous stress, cytokine levels, and the immunostaining for cyclooxygenase 2 and nuclear factor kappa B. Key findings Liver injured by nimesulide and treated with phosphatidylinositol 3-kinase gamma inhibitor significantly reversed (P < 0.05) the damage; it decreased the liver weight/animal weight ratio, histopathological scores, and neutrophil infiltration, consequently reducing oxidative stress. In addition, we show that phosphatidylinositol 3-kinase gamma is associated with hepatic damage induced by nimesulide, because it altered liver function and increased the protein immunostaining of cyclooxygenase 2 and nuclear factor kappa B in the liver tissue of nimesulide-treated animals. Conclusions The findings from the present study allows us to infer that nimesulide causes liver damage through the phosphatidylinositol 3-kinase gamma pathway. |
| Databáze: | OpenAIRE |
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