Protective effect of lyophilized recombinant human brain natriuretic peptide on renal ischemia/reperfusion injury in mice

Abstract

ABSTRACT. Brain natriuretic peptide (BNP) has a protective effect on acute injury of the heart, brain, and lung. However, its role in acute kidney injury (AKI) remains unclear. The aim of this study was to investigate the effect of lyophilized recombinant human BNP (lrh-BNP) on AKI and the underlying molecular mechanisms. An experimental model for AKI was established using an ischemia/reperfusion (I/R) procedure. Healthy adult BALB/c mice were randomized to the sham, I/R, and lrh-BNP-treated post-I/R (BNP + I/R) groups. Post-operatively, the BNP + I/R group was subcutaneously injected with lrh-BNP (0.03 µg·kg -1 ·min -1 ), whereas the other groups received saline at the same dose. Serum creatinine (Scr) and blood urea nitrogen levels were examined; tissue staining was performed to evaluate the degree of I/R injury (IRI). Ki67 positive staining of renal tubular epithelial cells was observed using immunofluorescence confocal laser scanning to assess the effect of BNP on cell proliferation after IRI. Inflammatory factor expression levels were detected to evaluate the effect of BNP on renal inflammation. Compared with the sham group, the I/R 13301 Effect of BNP on renal IRI ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 13300-13311 (2015) group showed increased Scr levels, severe tubular injury of the renal outer medulla, increased Kim-1 mRNA expression, an increased number of infiltrative macrophages in the renal interstitium, and increased TNF-α, IL-1β, IL-6, MCP-1, and HIF-1α mRNA expression. BNP delivery significantly reduced all pathological changes in the I/R group. The protective role of BNP in murine renal IRI may be associated with its inhibition of renal interstitial inflammation and hypoxia and its promotion of renal tubule repair.

Natriuretic Peptides: The Case of Prostate Cancer

“…Given that the ANP-dependent biological responses occur via its binding to NPRA, expressed in different type of immune cells [ 34 ], it has been reasonably suggested that, by autocrine/paracrine mechanisms [ 24 , 35 ], ANP exerts anti-inflammatory and immune-modulatory effects in the tissue microenvironment [ 20 ]. A similar biological effect based on similar molecular mechanisms, i.e., NF-κB and NALP3/ASC/Caspase-1 cascade inhibition, has been recently described for BNP [ 36 ], further supporting the anti-inflammatory role of this peptide [ 8 , 13 , 32 , 37 , 38 , 39 , 40 , 41 ]. As for direct effects on adaptive immunity, ANP/BNP reduce the number of CD4 + CD8 + lymphocytes while increasing the CD4 − CD8 − cells and stimulate the differentiation of naïve CD4 + cells toward the Th2 and/or Th17 phenotype [ 42 ].…”

Recombinant Human Brain Natriuretic Peptide Attenuates Myocardial Ischemia-Reperfusion Injury by Inhibiting CD4+ T Cell Proliferation via PI3K/AKT/mTOR Pathway Activation

“…. Sixty mice were divided into three groups (n = 6 per group): sham + phosphate-buffered saline (PBS), IR + PBS, and IR + rhBNP, consistent with the prior publication [17,18]. The mice were received an intraperitoneal injection of 0.035 mg of rhBNP or isopyknic PBS every other day for a total of three times after performing the IR surgery.…”

“…Recombinant human BNP (rhBNP) is a man-made peptide, developed through gene engineering, that is widely used to manage acute uncompensated congestive heart failure in patients [12]. Recently, rhBNP has also been administered intravenously to guide fluid therapy and predict outcomes of acute illness including IR injury in critical care units [17]. However, the effect of rhBNP on myocardial IR injury and the underlying mechanism for this remains unclear.…”

Perioperative “remote” acute lung injury: recent update

“…It has been reported that in patients, ALI is associated with signifi-cantly increased level of systemic BNP, which may represent up-regulated compensatory response 101-102 . In animal models of ALI, administration of recombinant human BNP has been shown to reduce the severity of lung injury, as well as the associated inflammatory response and oxidative stress 103-104 . However, more studies are needed to further validate both the diagnostic and therapeutic value of BNP in humans.…”