The protective effect of erythropoietin pretreatment on ischemic acute renal failure in rats

Role of erythropoietin in methotrexate-induced nephrotoxicity in adult male albino rats

“…The renoprotective effect of EPO is verified by Baek et al, Brøchner et al, Khalid et al who detected an excessive release of interleukins and tumor necrosis factor in case of IRI both in local renal tissue and generalized in the blood and interpreted that EPO diminished the contents of these inflammatory mediators in both locations through extrahematopoietic inhibitory action of EPO on the release of these mediators (35)(36)(37). Additionally, as mentioned before, Lee et al (38); O'Neill et al (39), Chen et al (40), Ozbilgin et al ( 41) , and Liao et al (16) confirmed that ischemic reperfusion of the kidney was associated with local (in the renal tissue) overexpressed TLR4 receptor which triggers NK-kB and local overexpressed NF-kB protein receptor that enhances the interleukins and tumor necrosis factor transcriptions and they accounted that the expression of these inflammatory mediators was suppressed with EPO management indicating that EPO could minimize the synthesis of these mediators through inhibition of the TLR4/NFkB pathway.…”

“…Our results simulated those of Liao et al who found a decrease of BUN and serum creatinine levels in EPO-treated group of rats within 4, 12 and 24 hours following renal reperfusion than their values in rat group having renal ischemic injury and therefore, they confirmed the defensive EPO effect on the renal ischemia. In addition, they verified that the pathologic renal ischemic changes have been attributed to renal cellular apoptosis, endothelial injury of the renal vessels, oxidative stress of the renal tissue and the inflammatory reaction within the kidney (16). Our group 3 results were identical to those of Zafirov et al who distinguished a decreased proteinuria in the group of rats treated with EPO which exerted its renoprotective action due to an induction of proliferative and regenerative capacities of the tubular cells and consequently avoid the renal damaging effect of cisplatin drug (29).…”

“…These findings coincided with those detected by Sharbaf et al who stated that the amount of oncotherapeutic drug in the tubular cells of the kidney exceeds several times its amount in the extracellular compartment and its major uptake occurs in the proximal renal tubules (24). In addition, Liao et al found a significant rise in both blood BUN and creatinine levels in the ischemic rat kidney at 4, 12 and 24 hours following renal reperfusion and they indicated a damage of the renal parenchymal tissue after reperfusion of ischemia so that the renal excretory capacity of urea nitrogen and creatinine was largely diminished (16). Smeland et al together with Messmann and Allegra stated that MTX-induced renal nephrotoxicity occurs due to either renal tubular precipitation of the drug or its metabolites or direct renal tubular damaging effect of the drug (25,26).…”

“…However, toll-like receptors (TLRs) are thought to be the keystone molecules in the regulation of inflammatory responses. Also, significantly increased expression of TLR4 from the renal tubular epithelial cells is confirmed and therefore, it activates the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and helps the expression of various inflammatory factors detected in IRI (16).…”

Correction of morphofunctional disorders with asialoerythropoietin and selective inhibitor of arginase II KUD975 in cases of ischemic kidney damage in the experiment

“…The main targets of erythropoietin when causing a renoprotective effect are mitochondrial K + ATP channels (ATP-dependent K + channels) and NO biosynthesis. Activation of mitochondrial K + ATP channels not only protects mitochondria from damage, but also affects the activity of transcription factors: increases the expression of HIF (Bahlmann and Fliser 2009), reduces the activity of NF-κB (Liao et al 2016), and has anti-apoptotic effects (Moore and Bellomo 2011). Renoprotective effects of erythropoietin were confirmed in a clinical study: the use of erythropoietin at a dose of 300 IU/kg in patients during coronary artery bypass surgery reduced the incidence of acute kidney injury (Song et al 2009).…”