Effects of sirolimus alone or in combination with cyclosporine A on renal ischemia/reperfusion injury

Pereira, Benedito Jamilson Araújo; Castro, Isac de; Burdmann, Emmanuel A.; Malheiros, Denise Maria Avancini Costa; Yu, Liang

doi:10.1590/s0100-879x2010007500058

Cited by 10 publications

(13 citation statements)

References 32 publications

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“…Since the ROS production is exceedingly high during IR, free radicals damage nephron epithelia as well as alter the microcirculatory system (afferent and efferent), and thus reduce the glomerular filtration rate (GFR) (22,23). Animals pretreated with SAB (20 and 40 mg·kg -1 ·day -1 ) showed a considerable decrease in the levels of Cr and BUN, due to its free radical scavenging activity.…”

Section: Discussionmentioning

confidence: 99%

“…During renal ischemic condition, neutrophils start to infiltrate into the damaged renal tissue (due to elevated oxidative stress) and stimulate pro-inflammatory markers, which would further promote neutrophil infiltration. This process blocks the microcirculation in the renal tissue, resulting in further renal damage and thereby affecting GFR (22,23). Both SAB 20 and 40 concomitantly reduced the MPO levels to near normal, due to its anti-inflammatory and antioxidant activity.…”

Section: Discussionmentioning

confidence: 99%

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Attenuation of renal ischemic reperfusion injury by salvianolic acid B via suppressing oxidative stress and inflammation through PI3K/Akt signaling pathway

Ma¹,

Xia²,

Cui³

et al. 2017

Braz J Med Biol Res

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Salvianolic acid B (SAB) is one the major phytocomponents of Radix Salvia miltiorrhiza and exhibit numerous health promoting properties. The objective of the current study was to examine whether SAB exerts a renoprotective effect by attenuating oxidative stress and inflammatory response through activating phosphatidylinositol 3-kinase/serine-threonine kinase B (PI3K/ Akt) signaling pathway in a renal ischemic reperfusion rat model. Forty Sprague-Dawley male rats (250-300 g) were obtained and split into four groups with ten rats in each group. The right kidney of all rats was removed (nephrectomy). The rats of the Control group received only saline (occlusion) and served as a sham control group, whereas rats subjected to ischemic reperfusion (IR) insult by clamping the left renal artery served as a postitive control group. The other 2 groups of rats were pretreated with SAB (20 and 40 mg Á kg -1 Á day -1 ) for 7 days prior IR induction and served as treatment groups (SAB 20+IR; SAB 40+IR). Renal markers creatinine (Cr) and blood urea nitrogen (BUN) were significantly lower in the groups that received SAB. Pretreatment with SAB appears to attenuate oxidative stress by suppressing the production of lipid peroxidation products like malondialdehyde as well as elevating antioxidant activity. The concentration of inflammatory markers and neutrophil infiltration (myeloperoxidase) were significantly decreased. Meanwhile, PI3K protein expression and pAkt/Akt ratio were significantly upregulated upon supplementation with SAB, indicating its renoprotective activity. Taken together, these results indicate that SAB can therapeutically alleviate oxidative stress and inflammatory process via modulating PI3K/Akt signaling pathway and probably ameliorate renal function and thus act as a renoprotective agent.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Attenuation of renal ischemic reperfusion injury by salvianolic acid B via suppressing oxidative stress and inflammation through PI3K/Akt signaling pathway

Ma¹,

Xia²,

Cui³

et al. 2017

Braz J Med Biol Res

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“…This intrinsic ‘stress system’ provokes transcription of genes such as glucose‐related protein‐78 (GRP‐78) or BiP, with the aim of re‐establishing normal function. Pereira et al41,42 demonstrated that the calcineurin inhibitor, cyclosporine (CsA), may trigger upregulation of the ER stress marker, BiP, in kidney transplant biopsies 41,42. If stress is overwhelming or prolonged, apoptotic pathways activate CHOP or GADD‐153, inducing DNA damage and downregulating Bcl‐2 while enhancing the actions of tumor necrosis factor receptor‐associated factor‐2 (TRAF‐2) and caspase 12 43.…”

Section: Mechanisms and Pathophysiology Of Kidney Injurymentioning

confidence: 99%

Ischemic kidney injury and mechanisms of tissue repair

Sabbahy

Vaidya

2010

WIREs Mechanisms of Disease

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Acute kidney injury (AKI) may result from ischemia or by the use of nephrotoxic agents. The incidence of AKI is variable, depends on comorbidities, and ranges from 5 to 35% in all hospitalized patients. The mechanisms of kidney injury exist within a large network of signaling pathways driven by interplay of inflammatory cytokines/chemokines, reactive oxygen species (ROS), and apoptotic factors. The effects and progression of injury overlap extensively with the remarkable ability of the kidney to repair itself both by intrinsic and extrinsic mechanisms that involve specific cell receptors/ligands as well as possible paracrine influences. The fact that kidney injury is usually part of a generalized comorbid condition makes it all the more challenging in terms of assessment of severity. In this review, we attempt to analyze the mechanisms of ischemic injury and repair in acute and chronic kidney disease from the perspectives of both preclinical and human studies.

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“…10,48 Cyclosporine minimization using sirolimus may improve the renal function in short term 49,50 and long term, 51 but its maintained exposure is still progressively nephrotoxic over time. 50 On the other hand, sirolimus can synergize with CNIs, 52,53 increase the nephrotoxicity of cyclosporine, 9,10,12,13,54 and decrease the glomerular filtration rate. 6 In renal allograft recipients, early and complete withdrawal of cyclosporine is more preferable than continuing this regimen.…”

Section: Combination Therapy By Cyclosporine and Sirolimusmentioning

confidence: 99%

“…31,48,55 Calcineurin inhibitors exacerbate ischemic injury in transplanted kidneys, but sirolimus has no such direct hypoxic effects yet it prevents cyclosporine-induced toxicity in the ischemic kidneys. 52 Effects of sirolimus on mycophenolate mofetil Some studies revealed the advantages of sirolimus and the disadvantages of cyclosporine on mycophenolate mofetil. Low-dose sirolimus therapy in combination with concentration-adjusted mycophenolate mofetil therapy leads to the improvement of organ function late after renal transplant.…”

Section: Combination Therapy By Cyclosporine and Sirolimusmentioning

confidence: 99%

Conversion of Calcineurin Inhibitors With Mammalian Target of Rapamycin Inhibitors After Kidney Transplant

Nikoueinejad

Soleimani²,

Mirshafiey³

et al. 2012

Exp Clin Transplant

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One way to overcome chronic allograft nephropathy induced by calcineurin inhibitors in immunosuppression protocols for organ transplants is to replace such inhibitors with mammalian target of rapamycin inhibitors, which are not clinically nephrotoxic because they have better renal function. If patients tolerate replacement, there could be a clear preference for mammalian target of rapamycin inhibitors as a maintenance immunosuppressant after renal transplant. This replacement could be sufficient if it were used for a certain time after calcineurin inhibitors. This review considers the conversion effects of calcineurin inhibitors with mammalian target of rapamycin inhibitors from the view point of kidney function during different periods after a kidney transplant.

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Effects of sirolimus alone or in combination with cyclosporine A on renal ischemia/reperfusion injury

Cited by 10 publications

References 32 publications

Attenuation of renal ischemic reperfusion injury by salvianolic acid B via suppressing oxidative stress and inflammation through PI3K/Akt signaling pathway

Attenuation of renal ischemic reperfusion injury by salvianolic acid B via suppressing oxidative stress and inflammation through PI3K/Akt signaling pathway

Ischemic kidney injury and mechanisms of tissue repair

Conversion of Calcineurin Inhibitors With Mammalian Target of Rapamycin Inhibitors After Kidney Transplant

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