Amelioration of Steatohepatitis with Pentoxifylline in a Novel Nonalcoholic Steatohepatitis Model Induced by High-Fat Diet

Yalnız, Mehmet; Bahçecıoğlu, İbrahim Halil; Kuzu, Nalan; Çelebi, Selman; Ataseven, Hüseyin; Üstündağ, Bilal; Özercan, İbrahim Hanifı; Şahin, Kazım

doi:10.1007/s10620-006-9194-1

Cited by 32 publications

(28 citation statements)

References 25 publications

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“…The results showed decreased AST levels but not ALT, and improvements in basal glucose but not HOMAIR index [19] . Additionally, in a previous study of Sprague-Dawley fed HFD for 10 wk and treated with pentoxifylline for 6 wk (50 mg/kg per day), hepatic steatosis and plasma levels of TNF-α were reduced [20] . In our work, we evaluated both hepatic and adipose tissue TNF-α levels and found that pentoxifylline treatment reduced both.…”

Section: Metabolic and Anthropometric Parameters After Pentoxifyllinementioning

confidence: 87%

Role of pentoxifylline in non-alcoholic fatty liver disease in high-fat diet-induced obesity in mice

Acedo¹

2015

WJH

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AIM: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 highfat 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 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 nontreated 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. CONCLUSION: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.

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Section: Metabolic and Anthropometric Parameters After Pentoxifyllinementioning

confidence: 87%

Role of pentoxifylline in non-alcoholic fatty liver disease in high-fat diet-induced obesity in mice

Acedo¹

2015

WJH

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“…They determined that after 2 weeks of 4.5 mg/ kg/day intraperitoneal pentoxifylline treatment, AST and ALT levels were significantly decreased in the pentoxifylline group compared to the group receiving placebo. When evaluated histopathologically, the density of steatosis inflammatory cells (/mm³) and ballooning degeneration were significantly lower in pentoxifylline group (26).…”

Section: Yalcin Et Al Non-alcoholic Steatohepatitismentioning

confidence: 94%

“…In rat models and human studies, pentoxifylline has been shown to improve transaminase levels and liver histopathology (23,24,25,26).…”

Section: Original Articlementioning

confidence: 99%

A comparison of the effects of infliximab, adalimumab, and pentoxifylline on rats with non-alcoholic steatohepatitis

Yalçın

Akarsu²,

Çelik³

et al. 2015

Turk J Gastroenterol

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Background/Aims: Non-alcoholic steatohepatitis (NASH) lacks effective medical treatment.Since tumor necrosis factor alpha (TNF-α) plays an important role in NASH pathogenesis, we aimed to investigate drugs affecting TNF-α as possible treatment options during the development of NASH. Materials and Methods: A total of 35 rats were divided into five groupsand evaluated over a 6week period. One group received a normal diet alone or in combination with the administration of infliximab, adalimumab or pentoxifylline Results: NASH was successfully established in the MCD diet group. Levels of TNF-α were effectively suppressed in the three groups that received anti-TNF agents. No statistically significant differences were observed between the three agents in terms of the histological NASH score. Conclusion: Our study showed that the anti-TNF agents infliximab, adalimumab, and pentoxifylline effectively suppress TNF-α. Although these drugs did not prevent the development of NASH, they were able to slightly reverse the NASH histopathology score and positively affect liver function tests

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“…PTX has been reported to be a possible agent for the treatment of steatohepatitis (Yalniz et al, 2007), sepsis (Selim et al, 2004), kidney disease (Ducloux et al, 2001), as well as cancer (Rauko P et al, 1998;Rishi et al, 2009). In the NASH animal model, PTX significantly ameliorated the histopathological lesions associated with NASH and decreased the aminotransferase levels by its antioxidative and anti-TNF-α effects (Yalniz et al, 2007). Prior to these findings, the only clinically confirmed treatment of NASH was weight reduction (Moschen and Tilg, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…PTX also has anti-oxidant activity as well as anti-TNF-α (Zabel et al, 1993) and anti-nuclear factor-κB (NF-κB) effects (Strieter et al, 1988). In a recent study carried out in a nonalcoholic steatohepatitis (NASH) mouse model, PTF administrated intra-abdominally significantly ameliorated NASH by inhibiting TNF-α and suppressing oxidative stress markers (Yalniz et al, 2007). Due to its anti-inflammatory, antioxidant and improved circulatory effects, PTF might improve the chronic inflammatory condition associated with obesity.…”

Section: Introductionmentioning

confidence: 99%

Pentoxifylline Induces Lipolysis and Apoptosis of Human Preadipocytes, Keratinocytes and Fibroblasts In Vitro

Lee¹,

Choi

Shim³

et al. 2010

Biomolecules and Therapeutics

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-Pentoxifylline (PTX) has been used for the local reduction of fat tissue in the clinical setting. However, its safety and efficacy have not been proven. The aim of this study was to evaluate the effects of PTX on cell lines established from fat tissue. Newly cultured human preadipocytes and adipocytes from subcutaneous abdominal fat in addition to purchased human lung fibroblasts and keratinocytes were treated with PTX at different concentrations. Cell viability was determined using the Cell counting kit (CCK)-8 assay and lipolysis was evaluated using an Elisa kit. DNA fragmentation, Western blot analysis, Hoechst and Propidium Iodide (PI) staining and fluorescence activated cell scanning analysis were performed to confirm apoptosis. The viability of adipocytes, preadipocytes, keratinocytes and fibroblasts was markedly decreased at concentrations of PTX above 20 mM. Apoptosis was induced at concentrations of PTX over 40 mM in all cell lines. Lipolysis was increased by 60% at concentrations of PTX of 20 mM compared to the control. In conclusion, the results of this study showed that 20 mM of PTX induced lipolysis. At concentrations over 20 mM, PTX reduced the viability of all cells studied including: adipocytes, preadipocytes, fibroblasts and keratinocytes, in a non-specific manner.

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Amelioration of Steatohepatitis with Pentoxifylline in a Novel Nonalcoholic Steatohepatitis Model Induced by High-Fat Diet

Cited by 32 publications

References 25 publications

Role of pentoxifylline in non-alcoholic fatty liver disease in high-fat diet-induced obesity in mice

Role of pentoxifylline in non-alcoholic fatty liver disease in high-fat diet-induced obesity in mice

A comparison of the effects of infliximab, adalimumab, and pentoxifylline on rats with non-alcoholic steatohepatitis

Pentoxifylline Induces Lipolysis and Apoptosis of Human Preadipocytes, Keratinocytes and Fibroblasts In Vitro

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