Pentoxifylline and melatonin in combination with pioglitazone ameliorate experimental non-alcoholic fatty liver disease

Zaitone, Sawsan A.; Hassan, Neven H.; El-Orabi, Naglaa F.; El-Awady, El-Sayed

doi:10.1016/j.ejphar.2011.04.049

Cited by 57 publications

(77 citation statements)

References 55 publications

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“…In this regard, pentoxifylline has been found to be clinically efficacious in a number of inflammatory pathologies characterized by increased TNFα production including alcoholic liver disease and rheumatoid arthritis (Queiroz-Junior et al, 2013; Sidhu et al, 2012; Zaitone et al, 2011). Since TNFα is a key mediator of pulmonary toxicity induced by vesicants (Sunil et al, 2011a), we tested the ability of pentoxifylline to mitigate NM-induced lung toxicity.…”

Section: Discussionmentioning

confidence: 99%

Pentoxifylline attenuates nitrogen mustard-induced acute lung injury, oxidative stress and inflammation

Sunil

Vayas

Cervelli

et al. 2014

Experimental and Molecular Pathology

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Nitrogen mustard (NM) is a toxic alkylating agent that causes damage to the respiratory tract. Evidence suggests that macrophages and inflammatory mediators including tumor necrosis factor (TNF)α contribute to pulmonary injury. Pentoxifylline is a TNFα inhibitor known to suppress inflammation. In these studies, we analyzed the ability of pentoxifylline to mitigate NM-induced lung injury and inflammation. Exposure of male Wistar rats (250 g; 8–10 weeks) to NM (0.125 mg/kg, i.t.) resulted in severe histolopathological changes in the lung within 3 d of exposure, along with increases in bronchoalveolar lavage (BAL) cell number and protein, indicating inflammation and alveolar-epithelial barrier dysfunction. This was associated with increases in oxidative stress proteins including lipocalin (Lcn)2 and heme oxygenase (HO)-1 in the lung, along with pro-inflammatory/cytotoxic (COX-2+ and MMP-9+), and anti-inflammatory/wound repair (CD163+ and Gal-3+) macrophages. Treatment of rats with pentoxifylline (46.7 mg/kg, i.p.) daily for 3 d beginning 15 min after NM significantly reduced NM-induced lung injury, inflammation, and oxidative stress, as measured histologically and by decreases in BAL cell and protein content, and levels of HO-1 and Lcn2. Macrophages expressing COX-2 and MMP-9 also decreased after pentoxifylline, while CD163+ and Gal-3+ macrophages increased. This was correlated with persistent upregulation of markers of wound repair including pro-surfactant protein-C and proliferating nuclear cell antigen by Type II cells. NM-induced lung injury and inflammation were associated with alterations in the elastic properties of the lung, however these were largely unaltered by pentoxifylline. These data suggest that pentoxifylline may be useful in treating acute lung injury, inflammation and oxidative stress induced by vesicants.

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Section: Discussionmentioning

confidence: 99%

Pentoxifylline attenuates nitrogen mustard-induced acute lung injury, oxidative stress and inflammation

Sunil

Vayas

Cervelli

et al. 2014

Experimental and Molecular Pathology

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“…Although downregulation of proinflammatory cytokines seems to be important for the protection or attenuation of injury it is possible that mitochondria were already highly damaged by the ischemic process. Previous studies have shown a beneficial effect of 50 mg/kg PTX supplementation to correct the overproduction of oxidative stress and inflammatory indices in IR-induced spinal cord injury and fatty liver disease 33,34 and a preventive effect for 400 mg/kg NAC was demonstrated in the rat organs against the oxidative damages. 35,36 Results of this study also demonstrated that beneficial effects of PTX were more than NAC.…”

Section: Discussionmentioning

confidence: 99%

Pretreatment with Pentoxifylline andN-Acetylcysteine in Liver Ischemia Reperfusion-Induced Renal Injury

et al. 2012

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“…In a study of PTX and melatonin in combination with pioglitazone in a non-alcoholic fatty liver disease (NAFLD) rat model, Zaitone et al (2011) documented that PTX reduced hepatic MDA and increased hepatic glutathione contents. It also induced a significant reduction in serum ALT activity.…”

Section: Fig 4 (A-i) Photomicrographs Of Liver Sections From (A) Comentioning

confidence: 98%

Hepatoprotective effects of early pentoxifylline administration on hepatic injury induced by concanavalin A in rat

Mohamed

Elmelegy

El-Aziz

et al. 2014

Can. J. Physiol. Pharmacol.

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Tumor necrosis factor alpha (TNF-α) plays an important role in the pathogensis of hepatitis C virus (HCV) infection induced liver injury. This study aimed to evaluate the effects of TNF-α inhibition with pentoxifylline (PTX) on concanavalin A (Con A)-induced hepatic injury in rats. The rats were distributed among 3 groups: (i) control group (1 mL saline·week(-1) by intravenous injection (i.v.)); (ii) Con A treatment group (20 mg Con A·(kg body mass)(-1)·week(-1), i.v.), and (iii) rats treated with Con A and with PTX (200 mg PTX·(kg body mass)(-1)·day(-1), per oral) group. Blood samples and livers were collected at the end of weeks 1, 2, 4, and 8 of Con A treatment. Portal pressure (PP) was measured at the end of week 8. The administration of PTX was found to confer significant protection against the injurious effects of Con A on the liver, by reducing serum levels of aspartate aminotransferase, alanine aminotransferase, hepatic TNF-α, and malondialdehyde. Histopathological examination revealed that treatment with PTX significantly suppressed early inflammation, reduced alpha smooth muscle actin, and the apoptosis of hepatocytes induced by Con A. Moreover, PTX significantly (P < 0.05) reduced PP, and quantitative analyses of the area of fibrosis induced by treatment with Con A showed a significant reduction at the end of week 8. We conclude that rats treated with PTX revealed a more or less normal hepatocyte architecture as well as marked improvement in fibrosis and PP.

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Pentoxifylline and melatonin in combination with pioglitazone ameliorate experimental non-alcoholic fatty liver disease

Cited by 57 publications

References 55 publications

Pentoxifylline attenuates nitrogen mustard-induced acute lung injury, oxidative stress and inflammation

Pentoxifylline attenuates nitrogen mustard-induced acute lung injury, oxidative stress and inflammation

Pretreatment with Pentoxifylline andN-Acetylcysteine in Liver Ischemia Reperfusion-Induced Renal Injury

Hepatoprotective effects of early pentoxifylline administration on hepatic injury induced by concanavalin A in rat

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