Phosphatidylinositol 3-kinase gamma participates in nimesulide-induced hepatic damage.

Pereira, Cynthia Maria C.; Dias Júnior, Genilson José; do N. Lima, José Victor; Alves Lemos, Sarah Izabelly; da Rocha Rodrigues, Lauanda; dos Santos Ferreira, Jayro; Miranda Loiola Araújo, Anna Sofia; Costa de Oliveira, Joveline; Eduardo Monteiro, Carlos; Xavier Franco, Álvaro; Pereira Alves, Even Herlany; Oliveira Silva, Francisca Géssica; de Carvalho Filgueiras, Marcelo; Soares, Pedro M. G.; Pereira Vasconcelos, Daniel Fernando; Soares de Oliveira, Jefferson; Vieira de Brito, Tarcisio; Reis Barbosa, André Luiz

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.

PHOSPHATIDYLINOSITOL 3-kinases; NF-kappa B; CYCLOOXYGENASE 2; OXYGENASES

Journal of Pharmacy & Pharmacology, 2021, Vol 73, Issue 4, p496

0022-3573

Academic Journal

10.1093/jpp/rgaa049