Potent antioxidant role of Pirfenidone in experimental cirrhosis

Salazar-Montes, Adriana; Ruiz-Corro, Luis; López‐Reyes, Alberto; Castrejón-Gómez, Eugenio; Armendáriz‐Borunda, Juan

doi:10.1016/j.ejphar.2008.06.110

Cited by 88 publications

(69 citation statements)

References 35 publications

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“…Hepatic growth factor (22), halofuginone (32) and adenovirus with urokinase plasminogen activator (25) induced collagen reduction in cirrhosis models. It should be pointed out that treatment with pirfenidone reduced 40% of the fibrosis induced by CCl 4 (23).…”

Section: Discussionmentioning

confidence: 99%

Modulation of extracellular matrix by nutritional hepatotrophic factors in thioacetamide-induced liver cirrhosis in the rat

Guerra

Trotta

Parra

et al. 2009

Braz J Med Biol Res

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Section: Discussionmentioning

confidence: 99%

Modulation of extracellular matrix by nutritional hepatotrophic factors in thioacetamide-induced liver cirrhosis in the rat

Guerra

Trotta

Parra

et al. 2009

Braz J Med Biol Res

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“…It gives the fibrosis index by calculating the ratio of type I collagen fibers (immunostained areas) to the whole liver area on a slide. 25,26 Histopathological evaluation was performed in four different sites per section for each treatment (n=7). The average value was then calculated for each experimental group to give the fibrosis index for each group.…”

Section: Fibrosis Index Calculationmentioning

confidence: 99%

MRI-based texture analysis: a potential technique to assess protectors against induced-liver fibrosis in rats

Mahmoud‐Ghoneim¹,

Amin²,

Corr³

2009

Radiology and Oncology

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“…PFD was reported to have exhibited anti-oxidative stress effects in mesangial cells and in a cirrhosis model (27,30). In the present study, a total antioxi-…”

Section: Effects Of Pfd Treatment On Antioxidant Activitymentioning

confidence: 73%

“…Oxidative stress is related to progressive renal injury (28). PFD is reported to exert antioxidative stress in mesangial cells and in a cirrhosis model (27,30). Therefore, the anti-inflammatory and anti-oxidative stress effects of PFD are also expected to ameliorate renal injury.…”

mentioning

confidence: 99%

Renoprotective mechanisms of pirfenidone in hypertension-induced renal injury: through anti-fibrotic and anti-oxidative stress pathways

Naito

Weng

et al. 2013

Biomed. Res.

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Pirfenidone (PFD) is a novel anti-fibrotic agent that targets TGFβ. However, the mechanisms underlying its renoprotective properties in hypertension-induced renal injury are poorly understood. We investigated the renoprotective properties of PFD and clarified its renoprotective mechanisms in a rat hypertension-induced renal injury model. Dahl salt-sensitive rats were fed a high-salt diet with or without 1% PFD for 6 weeks. During the administration period, we examined the effects of PFD on blood pressure and renal function. After the administration, the protein levels of renal TGFβ, Smad2/3, TNFα, MMP9, TIMP1, and catalase were examined. In addition, total serum antioxidant activity was measured. Compared to untreated rats, PFD treatment significantly attenuated blood pressure and proteinuria. Histological study showed that PFD treatment improved renal fibrosis. PFD may exert its anti-fibrotic effects via the downregulation of TGFβ-Smad2/3 signaling, improvement of MMP9/TIMP1 balance, and suppression of fibroblast proliferation. PFD treatment also increased catalase expression and total serum antioxidant activity. In contrast, PFD treatment did not affect the expression of TNFα protein, macrophage or T-cell infiltration, or plasma interleukin 1β levels. PFD prevents renal injury via its anti-fibrotic and anti-oxidative stress mechanisms. Clarifying the renoprotective mechanisms of PFD will help improve treatment for chronic renal diseases.Pirfenidone (PFD; 5-methyl-1-phenylpyridin-2-one) is an anti-fibrotic agent. PFD has been considered as an antagonist of transforming growth factor β (TGFβ), and has anti-fibrotic, anti-inflammatory, and antioxidative stress activities (6, 12-14, 27, 36). PFD has demonstrated an anti-fibrotic effect via the downregulation of TGFβ expression in several animal nephropathy models, including unilateral ureteral obstruction (36), diabetic nephropathy (24, 27), nephrectomy (35, 38), vanadate-induced renal fibrosis (1), and calcineurin inhibitor-induced nephrotoxicity (5,6,34). In addition, the clinical effectiveness of PFD has been evaluated in human diabetic nephropathy (32) and focal segmental glomerulosclerosis (7). The anti-fibrotic effect of PFD might also be due to the regulation of the balance of matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs) (6,10,20,36). Furthermore, PFD may also exert its anti-fibrotic effect via the suppression of fibroblast proliferation (14). PFD has demonstrated anti-inflammatory effects via the inhibition of the expressions of inflammatory mediators such as tumor necrosis factor α (TNFα) and interleukin 1β (IL1β) both in vivo and vitro (2,

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Potent antioxidant role of Pirfenidone in experimental cirrhosis

Cited by 88 publications

References 35 publications

Modulation of extracellular matrix by nutritional hepatotrophic factors in thioacetamide-induced liver cirrhosis in the rat

Modulation of extracellular matrix by nutritional hepatotrophic factors in thioacetamide-induced liver cirrhosis in the rat

MRI-based texture analysis: a potential technique to assess protectors against induced-liver fibrosis in rats

Renoprotective mechanisms of pirfenidone in hypertension-induced renal injury: through anti-fibrotic and anti-oxidative stress pathways

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