Experimental Models of Acute Renal Failure and Erythropoietin: What Evidence of a Direct Effect?

Sturiale, Alessio; Campo, Susanna; Crascì, Eleonora; Aloisi, Carmela; Buemi, Michele

doi:10.1080/08860220701193290

Cited by 8 publications

(4 citation statements)

References 73 publications

(66 reference statements)

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“…Moreover, several angiogenic growth factors, such as VEGF, appear to be essential intermediaries in the mechanisms by which relaxin exerts its vasodilator action in rats, mice and humans . This also applies to erythropoietin, even though the latter is able to stimulate angiogenesis also directly.…”

Section: Relaxin In Fibrosis and Cancer: A New Issue To Be Focusedmentioning

confidence: 99%

Relaxin: New Pathophysiological Aspects and Pharmacological Perspectives for an Old Protein

Cernaro

Lacquaniti

Lupica

et al. 2013

Medicinal Research Reviews

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Human relaxin-2 (hereafter simply defined as "relaxin") is a 6-kDa peptidic hormone best known for the physiological role played during pregnancy in the growth and differentiation of the reproductive tract and in the renal and systemic hemodynamic changes. This factor can also be involved in the pathophysiology of arterial hypertension and heart failure, in the molecular pathways of fibrosis and cancer, and in angiogenesis and bone remodeling. It belongs to the relaxin peptide family, whose members comprehensively exert numerous effects through interaction with different types of receptors, classified as relaxin family peptide (RXFP) receptors (RXFP1, RXFP2, RXFP3, RXFP4). Research looks toward the in-depth examination and complete understanding of relaxin in its various pleiotropic actions. The intent is to evaluate the likelihood of employing this substance for therapeutic purposes, for instance in diseases where a deficit could be part of the underlying pathophysiological mechanisms, also avoiding any adverse effect. Relaxin is already being considered as a promising drug, especially in acute heart failure. A careful study of the different RXFPs and their receptors and the comprehension of all biological activities of these hormones will probably provide new drugs with a potential wide range of therapeutic applications in the near future.

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Section: Relaxin In Fibrosis and Cancer: A New Issue To Be Focusedmentioning

confidence: 99%

Relaxin: New Pathophysiological Aspects and Pharmacological Perspectives for an Old Protein

Cernaro

Lacquaniti

Lupica

et al. 2013

Medicinal Research Reviews

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“…It has been speculated that EPO has anti-apoptotic effects in cardiovascular cells. These novel effects of EPO seem to be independent of its erythropoietic activity (for reviews [ 116,117 ]). Recent in vitro and in vivo studies have demonstrated that EPO attenuates experimental renal ischaemic/toxic cell damage [ 118,119 ] and there is an extensive physiological basis for using EPO also in clinical AKI [ 120 ].…”

Section: Erythropoietin (Epo)mentioning

confidence: 99%

The prevention of acute kidney injury an in-depth narrative review: Part 2: Drugs in the prevention of acute kidney injury

Lameire¹,

Biesen²,

Hoste

et al. 2009

Clinical Kidney Journal

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The second part of this in-depth clinical review focuses on drugs used in the prevention of AKI in the patient at risk and/or in the management of the patient with incipient AKI. Among the drugs used to maintain a normal renal perfusion pressure, norepinephrine and vasopressin are most commonly used in hypotensive critically ill patients. The most recent RCT did not find a difference between low-dose vasopressin plus norepinephrine and norepinephrine alone in patients with septic shock, suggesting that either approach is reasonable. However, vasopressin may be beneficial in the less severe septic shock subgroup. Loop diuretics may convert an oliguric into a non-oliguric form of AKI that may allow easier fluid and/or nutritional support of the patient. Volume overload in AKI patients is common and diuretics may provide symptomatic benefit in that situation. However, loop diuretics are neither associated with improved survival, nor with better recovery of renal function in AKI. Among the renal vasodilating drugs, the routine administration of dopamine to patients for the prevention of AKI or incipient AKI is no longer justified. On the other hand, although additional studies may be warranted, fenoldopam may appear to be a likely candidate for the prevention of AKI, particularly in critically ill patients, if the positive results obtained in some recent studies are confirmed. Trials with natriuretic peptides were in general inconclusive but despite the fact that nesiritide is currently approved by the FDA only for the treatment of heart failure, this vasodilator may in the future play a role in the prevention of AKI, particularly in association with heart failure and cardiac surgery. The most recent trials seem to confirm a potential positive preventive effect of N-acetylcysteine (NAC), particularly in contrast-induced nephropathy (CIN), NAC alone should never take the place of IV hydration in patients at risk for CIN; fluids likely have a more substantiated benefit. At present, initiation of statin therapy for the prevention of CIN cannot be recommended, but these drugs should not be stopped before a radiological intervention in patients on chronic statin therapy. Rasburicase is very effective in the prevention of acute tumour lysis syndrome. Erythropoietin (EPO) has tissue-protective effects and prevents tissue damage during ischaemia and inflammation, and currently trials are performed with EPO in the prevention of AKI post-cardiac surgery, CIN and post-kidney transplantation. From this review it becomes clear that single-drug therapy will probably never be effective in the prevention of AKI and that multiple agents may be needed to improve outcomes. In addition, drugs should be administered early during the course of the disease.

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“…By contrast, STAT3 also has anti-apoptotic properties. [88] In view of current clinical practice, drugs, hormones, receptor targeting or physical therapy could prevent apoptosis of neuronal cells by activating the signaling pathway with STAT3. Activated by JAK2/STAT3 pathway, STAT3 exerts the neuroprotective function.…”

Section: The Mechanism Of Ciri Based On Jak/stat Signaling Pathwaymentioning

confidence: 99%

The role of JAK/STAT signaling pathway in cerebral ischemia-reperfusion injury and the therapeutic effect of traditional Chinese medicine: A narrative review

Song,

Zhang,

Zhu

et al. 2023

Medicine

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Cerebral ischemia is a cerebrovascular disease with symptoms caused by insufficient blood or oxygen supply to the brain. When blood supplied is restored after cerebral ischemia, secondary brain injury may occur, which is called cerebral ischemia-reperfusion injury (CIRI). In this process, the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway plays an important role. It mediates neuroinflammation and participates in the regulation of physiological activities, such as cell proliferation, differentiation, and apoptosis. After CIRI, M1 microglia is activated and recruited by the damaged tissue. The inflammatory factors are produced by M1 microglia through the JAK/STAT pathway, eventually leading to cell apoptosis. Meanwhile, the JAK2/STAT3 signaling pathway and the expression of lipocalin-2 and caspase-3 could increase. In the pathway, phosphorylated JAK2 and phosphorylated STAT3 function of 2 ways. They not only promote the proliferation of neurons, but also affect the differentiation direction of neural stem cells by further acting on the Notch signaling pathway. Recently, traditional Chinese medicine (TCM) is a key player in CIRI, through JAK2, STAT3, STAT1 and their phosphorylation. Therefore, the review focuses on the JAK/STAT signaling pathway and its relationship with CIRI as well as the influence of the TCM on this pathway. It is aimed at providing the basis for future clinical research on the molecular mechanism of TCM in the treatment of CIRI.

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Experimental Models of Acute Renal Failure and Erythropoietin: What Evidence of a Direct Effect?

Cited by 8 publications

References 73 publications

Relaxin: New Pathophysiological Aspects and Pharmacological Perspectives for an Old Protein

Relaxin: New Pathophysiological Aspects and Pharmacological Perspectives for an Old Protein

The prevention of acute kidney injury an in-depth narrative review: Part 2: Drugs in the prevention of acute kidney injury

The role of JAK/STAT signaling pathway in cerebral ischemia-reperfusion injury and the therapeutic effect of traditional Chinese medicine: A narrative review

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