Long-term protective effect of UR-12670 after warm renal ischemia in uninephrectomized rats

Torrás, Joan; Cruzado, Josep M.; Riera, Marta; Condom, Enric; Duque, Natalia; Herrero, I.; Espinosa, Lluis; Lloberas, Núria; Egido, Jesús; Grinyó, Josep M.

doi:10.1046/j.1523-1755.1999.00724.x

Cited by 31 publications

(18 citation statements)

References 35 publications

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“…This is in accordance with previous studies that showed, in isolated perfused rat kidney, that the addition of PAF induced proteinuria, at similar levels to that induced by angiotensin II. 35 In addition, Torras et al 36 showed that longterm pharmacological blockade of PAFR protects from progressive renal injury. On the other hand, another work did not observe any difference concerning albuminuria levels between animals treated or not with PAFR antagonist in the ablation model of CKD.…”

Section: Discussionmentioning

confidence: 99%

Activation of platelet-activating factor receptor exacerbates renal inflammation and promotes fibrosis

Corrêa-Costa

Andrade-Oliveira

Braga

et al. 2014

Laboratory Investigation

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Platelet-activating factor (PAF) is a lipid mediator with important pro-inflammatory effects, being synthesized by several cell types including kidney cells. Although there is evidence of its involvement in acute renal dysfunction, its role in progressive kidney injury is not completely known. In the present study, we investigated the role of PAF receptor (PAFR) in an experimental model of chronic renal disease. Wild-type (WT) and PAFR knockout (KO) mice underwent unilateral ureter obstruction (UUO), and at kill time, urine and kidney tissue was collected. PAFR KO animals compared with WT mice present: (a) less renal dysfunction, evaluated by urine protein/creatinine ratio; (b) less fibrosis evaluated by collagen deposition, type I collagen, Lysyl Oxidase-1 (LOX-1) and transforming growth factor b (TGF-b) gene expression, and higher expression of bone morphogenetic protein 7 (BMP-7) (3.3-fold lower TGF-b/BMP-7 ratio); (c) downregulation of extracellular matrix (ECM) and adhesion molecule-related machinery genes; and (d) lower levels of pro-inflammatory cytokines. These indicate that PAFR engagement by PAF or PAF-like molecules generated during UUO potentiates renal dysfunction and fibrosis and might promote epithelial-to-mesenchymal transition (EMT). Also, early blockade of PAFR after UUO leads to a protective effect, with less fibrosis deposition. In conclusion, PAFR signaling contributes to a pro-inflammatory environment in the model of obstructive nephropathy, favoring the fibrotic process, which lately will generate renal dysfunction and progressive organ failure.

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Section: Discussionmentioning

confidence: 99%

Activation of platelet-activating factor receptor exacerbates renal inflammation and promotes fibrosis

Corrêa-Costa

Andrade-Oliveira

Braga

et al. 2014

Laboratory Investigation

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“…si on in jury to the he art musc le, 19 a pro tec ti on against isc he mic in jury to the kid ney, 20 a re duc ti on of the isc he mi a-re per fu si on da ma ge to the lung, 21 and an ame li o ra ti on of the isc he mi a-re per fu si on in jury to the li ver. 22 The se re sults ha ve led us to at tempt to tre at ment by a PAF an ta go nist ABT-491 in models of HI.…”

Section: Fi Gu Rementioning

confidence: 99%

Protective Effects of Platelet-Activating Factor Antagonist ABT-491 on the Peripheral Nerves in Hypoxic Ischemia-Induced Neonatal Rat Model

Büyükakıllı¹,

Atıcı²,

Büyükdereli³

et al. 2011

Turkiye Klinikleri J Med Sci

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A AB BS S T TR RA AC CT T O Ob b j je ec c t ti i v ve e: : Ne o na tal hypo xic-isc he mic (HI) in sult has acu te and long term de le te ri ous ef fects on many tis su es inc lu ding the pe rip he ral ner ves. To da te, no study has in ves ti ga ted the ro le of pla te let-ac ti va ting fac tor (PAF) an ta go nists on pe rip he ral ner ve da ma ge in a ne o na tal rat mo del of HI. In this study, we exa mi ned the ef fects of PAF an ta go nist (ABT-491) on pe rip he ral ner ve da ma ge in rats in the 16th we ek that we re ex po sed to HI on 7th day af ter birth. M Ma a t te e r ri i a al l a an nd d M Me et t h ho od ds s: : Se ven-day-old Wis tar rat pups we re sub jec ted to right com mon ca ro tid ar tery li ga ti on and hypo xi a (92% nit ro gen and 8% oxy gen) for one ho ur. They we re tre a ted eit her with ABT-491 (n=19) or sa li ne (n=20) im me di a tely af ter hypo xi a. In sham gro up (n=20), ne it her li ga ti on nor hypo xi a was per for med. The com po und mo tor ac ti on po ten ti al (CMAP) re cor dings of all ani mals we re ma de in the six te enth we ek fol lo wing the HI. For CMAP re cor dings, bi po lar sti mu la ting elec tro des we re pla ced on the sci a tic ner ve. Upon sti mu la ti on, two sur fa ce elec tro des, pla ced over the gas troc ne mi us musc le, re cor ded com po und musc le ac ti on po ten ti als. R Re e s su ul lt ts s: : The amp li tu de of CMAP re cor ded from the rats tre a ted with sa li ne af ter hypo xi a was smaller com pa red to the sham gro up. However, the CMAP re cor ded from the gro up tre a ted with ABT-491 af ter HI was not sig ni fi cantly dif fe rent from the sham gro up. C Co on nc c l lu u s si i o on n: : This study imp li es that HI has axo nal dama ge on pe rip he ral ner ve but a PAF an ta go nist ABT-491 has a pre ven ti ve ef fect on the axo nal dysfunc ti on af ter HI.K Ke ey y W Wo or rd ds s : : ABT-491; Action potentials; peripheral nerves; ischemia; anoxia Ö ÖZ ZE ET T A Am ma aç ç: : Ne o na tal hi pok sik-is ke mik (Hİ) ha sar pe ri fe rik si nir ler da hil bir çok do ku da kı sa ve uzun va de de za rar lı et ki ler gös te rir. Bu gü ne ka dar, Hİ 'ye ma ruz ka lan ye ni do ğan sı çan la rın pe rife rik si nir ha sa rı üze ri ne pla te let ak ti ve edi ci fak tör (PAF) an ta go nis ti nin ro lü araş tı rıl ma mış tır. Bu ça lış ma da PAF an ta go nis ti nin (ABT-491) do ğum dan son ra ki yedinci gün de Hİ' ye ma ruz ka lan sı -çan lar da 16. haf ta da ki pe ri fe rik si nir ha sa rı na et ki le ri ni in ce le dik. G Ge er re eç ç v ve e Y Yö ön nt te em ml le er r: : Ye di gün-lük Wis tar sı çan yav ru la rı sağ or tak ka ro tid ar ter li gas yo nu na ve bir sa at sü rey le hi pok si ye (%92 nit ro jen ve %8 ok si jen) ma ruz bı ra kıl dı lar. Hi pok si nin he men ar dın dan bir grup sı ça na ABT-491 (ABT Gru bu), di ğer bir grup sı ça na se rum fiz yo lo jik (Sa li n Gru bu) ve ril di. Üçün cü grup sı ça na (Sham Gru bu) li gas yon ve ya hi pok si uy gu lan ma dı. Bü tün hay van lar da Hİ' yi iz le yen onal tın cı hafta da bi le şik mo tor ak ...

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“…9 Treatment with several PAF antagonists has been reported in acute renal failure 10 and chronic renal failure animal models. 11,12 However, problems exist regarding the lack of specificity of PAF antagonists. [13][14][15][16] Therefore, we have developed genetically engineered PAFR-deficient (PAFR-KO) mice to confirm the role of PAF in vivo.…”

mentioning

confidence: 99%

Attenuation of Folic Acid-Induced Renal Inflammatory Injury in Platelet-Activating Factor Receptor-Deficient Mice

Doi

Okamoto

Negishi

et al. 2006

The American Journal of Pathology

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Platelet-activating factor (PAF), a potent lipid mediator with various biological activities, plays an important role in inflammation by recruiting leukocytes. In this study we used platelet-activating factor receptor (PAFR)-deficient mice to elucidate the role of PAF in inflammatory renal injury induced by folic acid administration. PAFR-deficient mice showed significant amelioration of renal dysfunction and pathological findings such as acute tubular damage with neutrophil infiltration, lipid peroxidation observed with antibody to 4-hydroxy-2-hexenal (day 2), and interstitial fibrosis with macrophage infiltration associated with expression of monocyte chemoattractant protein-1 and tumor necrosis factor-␣ in the kidney (day 14). Acute tubular damage was attenuated by neutrophil depletion using a monoclonal antibody (RB6-8C5), demonstrating the contribution of neutrophils to acute phase injury. Macrophage infiltration was also decreased when treatment with a PAF antagonist (WEB2086) was started after acute phase. In vitro chemotaxis assay using a Boyden chamber demonstrated that PAF exhibits a strong chemotactic activity for macrophages. These results indicate that PAF is involved in pathogenesis of folic acid-induced renal injury by activating neutrophils in acute phase and macrophages in chronic interstitial fibrosis. Inhibiting the PAF pathway might be therapeutic to kidney injury from inflammatory cells.

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Long-term protective effect of UR-12670 after warm renal ischemia in uninephrectomized rats

Cited by 31 publications

References 35 publications

Activation of platelet-activating factor receptor exacerbates renal inflammation and promotes fibrosis

Activation of platelet-activating factor receptor exacerbates renal inflammation and promotes fibrosis

Protective Effects of Platelet-Activating Factor Antagonist ABT-491 on the Peripheral Nerves in Hypoxic Ischemia-Induced Neonatal Rat Model

Attenuation of Folic Acid-Induced Renal Inflammatory Injury in Platelet-Activating Factor Receptor-Deficient Mice

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