Nanopartículas de ouro esféricas neutras atuam na resposta anti-inflamatória, antioxidante e antifibrotica em lesão hepática induzida por álcool e metanfetamina em ratos wistar

Abstract

This study aimed to elucidate the therapeutic effects of gold nanoparticles (GNPs) in rats with alcohol and methamphetamine-induced hepatic injury (METH). Hepatic injury was induced by administrations via gavage of 30% alcoholic solution (7 mg/kg) once daily for 28 days, followed by METH (10 mg/kg) on the 20th and 28th days of treatment. To evaluate the dose-dependent effect, doses of GNPs were fractionated at 724.96 μg/kg, 362.48 μg/kg and 181.48 μg/kg. After conducting Biodistribution tests the GNPs migrated to the liver, spleen, bladder, kidneys and brain. The GNPs were absorbed by the Kupffer cells in the liver, as observed in the tissue analysis. Treatment with GNPs (724.96 μg/kg) during the alcohol and METH protocol was associated with reduced steatosis, hepatic cord degeneration, fibrosis and necrosis, as well as reduced levels of AST, ALT, TG, MPO , MDA, GSH and proinflammatory cytokines IL-1β and TNF-α and increased levels of regulatory cytokines such as IL-10, when compared with the positive alcohol + METH control group. Treatment with 724.96 μg / kg of GNPs also reduced expression levels of TGF-β, FGF-1, SOD-1 and GPx-1 and decreased expression of proinflammatory cytokines such as IL-1β, TNF-α and MIF. There was a decrease in the expression of procollagen type I and III mRNA (PCI, PCIII), nuclear factor kappa B (NF-Kβ), macrophage specific adhesion (F4/80), protein kinase B (AKT) and phosphatidylinositol -4,5-bisphosphate 3-kinase (PI3K) in the alcohol treated group + METH + 724.96 μg / kg of GNPs in relation to the positive control group treated with alcohol + METH. GNPs reduced the activity of Kupffer cells and hepatic stellate cells that affected the proinflammatory cytokine stimulation profile, reduction of oxidative stress and consequently the development of hepatic fibrosis by modulating AKT / PI3K / ERK signaling pathways.