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Title in Portuguese: Dual effect of silymarin on experimental non-alcoholic steatohepatitis induced by irinotecan
Author: Assis-Júnior, Eudmar Marcolino
Melo, Anielle Torres
Pereira, Venúcia Bruna Magalhães
Wong, Deysi Viviana Tenazoa
Sousa, Nathalia Ribeiro Pinho
Oliveira, Christiane Mendes Gonçalves
Malveira, Lara Raissa Cavalcante
Moreira, Leonardo Silva
Souza, Marcellus Henrique Loiola Ponte
Almeida, Paulo Roberto Carvalho
Lima-Júnior, Roberto César Pereira
Keywords: Fígado
Neoplasias Hepáticas
Liver Diseases
Issue Date: Jul-2017
Publisher: Toxicology and Applied Pharmacology
Citation: ASSIS-JÚNIOR, E. M. et al. Dual effect of silymarin on experimental non-alcoholic steatohepatitis induced by irinotecan. Toxicology and Applied Pharmacology, New York, v. 327, p. 71-79, jul. 2017.
Abstract: Irinotecan-based regimens are commonly used for treatment of colorectal cancer, which is limited by mucositis and non-alcoholic steatohepatitis (NASH). Silymarin (SIL) prevents fatty liver disease in the clinical setting and in models of liver damage induced chemically. This study investigated the possible effect of SIL on irinotecan (IRI)-induced NASH. Swiss female mice were injected with saline (SAL 5 ml/kg i.p.), IRI (50 mg/kg i.p.), SIL (150 mg/kg p.o.) or IRI (50 mg/kg i.p.) + (SIL 1.5, 15 or 150 mg/kg p.o.) thrice/week/7 weeks. On the seventh week, blood samples were collected for transaminases assay and livers were collected for histopathology, measurement of the total lipids, malondyadehyde (MDA), non-protein sulfhydryl groups (NPSH), cytokines (IL-1β, IL 6 and IL-10), 3-nitrotyrosine (N-Tyr) and toll-like receptor 4 (TLR4) immunoexpression, quantification of NF-kB, α-smooth muscle actin (α-SMA), and Escherichia coli 16S rRNA gene (RRS) expression. IRI increased liver transaminases, neutrophil infiltration, lipid accumulation, MDA, IL-1β and IL-6 levels, N-Tyr and TLR4 immunostaining, NF-kB, α-SMA expression and RRS versus the SAL group (p < 0.05). Additionally, SIL (1.5 mg/kg) improved these parameters (p < 0.05), except neutrophil infiltration and RSS versus the IRI group. Furthermore, the SIL (15 mg/kg) only improved the inflammatory parameters, the expression of α-SMA and RRS versus the IRI group (p < 0.05). The higher dose of SIL (150 mg/kg) was even more deleterious than the intermediate dose. Therefore, silymarin showed a dual effect on liver damage induced by IRI. Hepatoprotection seems to involve the inhibition of oxidative stress and protein nitrosylation, preventing activation of hepatic fibrosis mechanisms.
metadata.dc.type: Artigo de Periódico
ISSN: 0041-008X
Appears in Collections:DCIR - Artigos publicados em revista científica

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