title: Role of pentoxifylline in non-alcoholic fatty liver disease in high-fat diet-induced obesity in mice.
abstract: OBJECTIVE
  To study pentoxifylline effects in liver and adipose tissue inflammation in obese mice induced by high-fat diet (HFD).
  
  
  METHODS
  Male swiss mice (6-wk old) were fed a high-fat diet (HFD; 60% kcal from fat) or AIN-93 (control diet; 15% kcal from fat) for 12 wk and received pentoxifylline intraperitoneally (100 mg/kg per day) for the last 14 d. Glucose homeostasis was evaluated by measurements of basal glucose blood levels and insulin tolerance test two days before the end of the protocol. Final body weight was assessed. Epididymal adipose tissue was collected and weighted for adiposity evaluation. Liver and adipose tissue biopsies were homogenized in solubilization buffer and cytokines were measured in supernatant by enzyme immunoassay or multiplex kit, respectively. Hepatic histopathologic analyses were performed in sections of paraformaldehyde-fixed, paraffin-embedded liver specimens stained with hematoxylin-eosin by an independent pathologist. Steatosis (macrovesicular and microvesicular), ballooning degeneration and inflammation were histopathologically determined. Triglycerides measurements were performed after lipid extraction in liver tissue.
  
  
  RESULTS
  Pentoxifylline treatment reduced microsteatosis and tumor necrosis factor (TNF)-α in liver (156.3 ± 17.2 and 62.6 ± 7.6 pg/mL of TNF-α for non-treated and treated obese mice, respectively; P < 0.05). Serum aspartate aminotransferase levels were also reduced (23.2 ± 6.9 and 12.1 ± 1.6 U/L for non-treated and treated obese mice, respectively; P < 0.05) but had no effect on glucose homeostasis. In obese adipose tissue, pentoxifylline reduced TNF-α (106.1 ± 17.6 and 51.1 ± 9.6 pg/mL for non-treated and treated obese mice, respectively; P < 0.05) and interleukin-6 (340.8 ± 51.3 and 166.6 ± 22.5 pg/mL for non-treated and treated obese mice, respectively; P < 0.05) levels; however, leptin (8.1 ± 0.7 and 23.1 ± 2.9 ng/mL for non-treated and treated lean mice, respectively; P < 0.05) and plasminogen activator inhibitor-1 (600.2 ± 32.3 and 1508.6 ± 210.4 pg/mL for non-treated and treated lean mice, respectively; P < 0.05) levels increased in lean adipose tissue. TNF-α level in the liver of lean mice also increased (29.6 ± 6.6 and 75.4 ± 12.6 pg/mL for non-treated and treated lean mice, respectively; P < 0.05) while triglycerides presented a tendency to reduction.
  
  
  CONCLUSIONS
  Pentoxifylline was beneficial in obese mice improving liver and adipose tissue inflammation. Unexpectedly, pentoxifylline increased pro-inflammatory markers in the liver and adipose tissue of lean mice.
authors.affiliation: Simone Coghetto Acedo, Cintia Rabelo e Paiva Caria, Érica Martins Ferreira Gotardo, José Aires Pereira, José Pedrazzoli, Marcelo Lima Ribeiro, Alessandra Gambero, Clinical Pharmacology and Gastroenterology Unit, São Francisco University Medical School, Bragança Paulista SP 12916-900, Brazil.
authors.forename: Simone Coghetto
authors.initials: SC
authors.lastname: Acedo
authors.affiliation: Simone Coghetto Acedo, Cintia Rabelo e Paiva Caria, Érica Martins Ferreira Gotardo, José Aires Pereira, José Pedrazzoli, Marcelo Lima Ribeiro, Alessandra Gambero, Clinical Pharmacology and Gastroenterology Unit, São Francisco University Medical School, Bragança Paulista SP 12916-900, Brazil.
authors.forename: Cintia Rabelo E Paiva
authors.initials: CR
authors.lastname: Caria
authors.affiliation: Simone Coghetto Acedo, Cintia Rabelo e Paiva Caria, Érica Martins Ferreira Gotardo, José Aires Pereira, José Pedrazzoli, Marcelo Lima Ribeiro, Alessandra Gambero, Clinical Pharmacology and Gastroenterology Unit, São Francisco University Medical School, Bragança Paulista SP 12916-900, Brazil.
authors.forename: Érica Martins Ferreira
authors.initials: ÉM
authors.lastname: Gotardo
authors.affiliation: Simone Coghetto Acedo, Cintia Rabelo e Paiva Caria, Érica Martins Ferreira Gotardo, José Aires Pereira, José Pedrazzoli, Marcelo Lima Ribeiro, Alessandra Gambero, Clinical Pharmacology and Gastroenterology Unit, São Francisco University Medical School, Bragança Paulista SP 12916-900, Brazil.
authors.forename: José Aires
authors.initials: JA
authors.lastname: Pereira
authors.affiliation: Simone Coghetto Acedo, Cintia Rabelo e Paiva Caria, Érica Martins Ferreira Gotardo, José Aires Pereira, José Pedrazzoli, Marcelo Lima Ribeiro, Alessandra Gambero, Clinical Pharmacology and Gastroenterology Unit, São Francisco University Medical School, Bragança Paulista SP 12916-900, Brazil.
authors.forename: José
authors.initials: J
authors.lastname: Pedrazzoli
authors.affiliation: Simone Coghetto Acedo, Cintia Rabelo e Paiva Caria, Érica Martins Ferreira Gotardo, José Aires Pereira, José Pedrazzoli, Marcelo Lima Ribeiro, Alessandra Gambero, Clinical Pharmacology and Gastroenterology Unit, São Francisco University Medical School, Bragança Paulista SP 12916-900, Brazil.
authors.forename: Marcelo Lima
authors.initials: ML
authors.lastname: Ribeiro
authors.affiliation: Simone Coghetto Acedo, Cintia Rabelo e Paiva Caria, Érica Martins Ferreira Gotardo, José Aires Pereira, José Pedrazzoli, Marcelo Lima Ribeiro, Alessandra Gambero, Clinical Pharmacology and Gastroenterology Unit, São Francisco University Medical School, Bragança Paulista SP 12916-900, Brazil.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Gambero
keywords: Adipokine; Adipose tissue; Obesity; Pentoxifylline; Steatosis; Tumor necrosis factor-α