Abstract:Ischemic reperfusion kidney injury (IRKI) is a complex pathophysiological event, which is the most common cause of the acute kidney injury. The key characteristic of IRKI is a reduction in glomerular filtration rate, which implies an underlying impairment in hemodynamic regulation. In recent decades, convincing evidence illuminated the molecular and pathological events in the acute kidney injury, revealing the role of ischemia/reperfusion, oxidative stress, apoptosis, inflammation, fibrosis and changes in gene… Show more
“…Recently, miRNAs have been involved in the cell response to I/R in kidney30. Related to this, here we demonstrated that in vivo HIF-1α interference leads to a lower expression of miR-127-3p and, consequently, increased expression of its target gene Bcl6, a transcriptional repressor involved in apoptosis31 and survival regulation32.…”
Ischemia/reperfusion (I/R) leads to Acute Kidney Injury. HIF-1α is a key factor during organ response to I/R. We previously demonstrated that HIF-1α is induced during renal reperfusion, after ischemia. Here we investigate the role of HIF-1α and the HIF-1α dependent mechanisms in renal repair after ischemia. By interference of HIF-1α in a rat model of renal I/R, we observed loss of expression and mis-localization of e-cadherin and induction of α-SMA, MMP-13, TGFβ, and collagen I. Moreover, we demonstrate that HIF-1α inhibition promotes renal cell infiltrates by inducing IL-1β, TNF-α, MCP-1 and VCAM-1, through NFkB activity. In addition, HIF-1α inhibition induced proximal tubule cells proliferation but it did not induce compensatory apoptosis, both in vivo. In vitro, HIF-1α knockdown in HK2 cells subjected to hypoxia/reoxygenation (H/R) promote cell entry into S phase, correlating with in vivo data. HIF-1α interference leads to downregulation of miR-127-3p and induction of its target gene Bcl6 in vivo. Moreover, modulation of miR-127-3p in HK2 cells subjected to H/R results in EMT regulation: miR127-3p inhibition promote loss of e-cadherin and induction of α-SMA and collagen I. In conclusion, HIF-1α induction during reperfusion is a protector mechanism implicated in a normal renal tissue repair after I/R.
“…Recently, miRNAs have been involved in the cell response to I/R in kidney30. Related to this, here we demonstrated that in vivo HIF-1α interference leads to a lower expression of miR-127-3p and, consequently, increased expression of its target gene Bcl6, a transcriptional repressor involved in apoptosis31 and survival regulation32.…”
Ischemia/reperfusion (I/R) leads to Acute Kidney Injury. HIF-1α is a key factor during organ response to I/R. We previously demonstrated that HIF-1α is induced during renal reperfusion, after ischemia. Here we investigate the role of HIF-1α and the HIF-1α dependent mechanisms in renal repair after ischemia. By interference of HIF-1α in a rat model of renal I/R, we observed loss of expression and mis-localization of e-cadherin and induction of α-SMA, MMP-13, TGFβ, and collagen I. Moreover, we demonstrate that HIF-1α inhibition promotes renal cell infiltrates by inducing IL-1β, TNF-α, MCP-1 and VCAM-1, through NFkB activity. In addition, HIF-1α inhibition induced proximal tubule cells proliferation but it did not induce compensatory apoptosis, both in vivo. In vitro, HIF-1α knockdown in HK2 cells subjected to hypoxia/reoxygenation (H/R) promote cell entry into S phase, correlating with in vivo data. HIF-1α interference leads to downregulation of miR-127-3p and induction of its target gene Bcl6 in vivo. Moreover, modulation of miR-127-3p in HK2 cells subjected to H/R results in EMT regulation: miR127-3p inhibition promote loss of e-cadherin and induction of α-SMA and collagen I. In conclusion, HIF-1α induction during reperfusion is a protector mechanism implicated in a normal renal tissue repair after I/R.
“…In oxygen deprivation, anaerobic glycolysis is enhanced, lactic acid is accumulated, mitochondrial dysfunction is enhanced, and production of ROS and superoxide is upregulated [53]. The injury expands after reperfusion that is characterized by inflammatory response with leukocyte and complements activation that progresses to an oxidant environment that cannot be counterbalanced by antioxidant mechanisms [54] and uneventfully leads to excessive cell death [53]. …”
Acute kidney injury (AKI) is a multifactorial entity that occurs in a variety of clinical settings. Although AKI is not a usual reason for intensive care unit (ICU) admission, it often complicates critically ill patients' clinical course requiring renal replacement therapy progressing sometimes to end-stage renal disease and increasing mortality. The causes of AKI in the group of ICU patients are further complicated from damaged metabolic state, systemic inflammation, sepsis, and hemodynamic dysregulations, leading to an imbalance that generates oxidative stress response. Abundant experimental and to a less extent clinical data support the important role of oxidative stress-related mechanisms in the injury phase of AKI. The purpose of this article is to present the main pathophysiologic mechanisms of AKI in ICU patients focusing on the different aspects of oxidative stress generation, the available evidence of interventional measures for AKI prevention, biomarkers used in a clinical setting, and future perspectives in oxidative stress regulation.
“…1 The damage is further complicated by the release of oxygen-derived free radicals into the tissue, although reperfusion is necessary for ischemic tissue survival. 2 Renal ischemia-reperfusion (R-IR) injury may be resulted in due to renal transplantation, shock, sepsis and surgical procedures despite great clinical efforts. 3 IR injury is the primary cause of high mortality in acute renal insuffi ciency, the R-IR model in fi ghting against this injury is used in experimental studies widely.…”
Aim The aim of this study is to evaluate the antioxidant effect of p-Coumaric Acid (p-CA) on tissue damage due to ischemia-reperfusion in rat kidney tissue. ( Sakarya Med J 2018, 8(3):625-631)Methods Thirty-two 12-16 week-old Wistar Albino female rats weighing 200-250 g were used in this study. Rats underwent right nephrectomy intraperitoneally with an incision made in the dorsal region under ketamine (75 mg/kg) and xylazine (8 mg/kg) anesthesia. These rats were randomly divided into four groups in equal numbers (n = 8). Groups were classifi ed as the sham (S), renal ischemia-reperfusion (R-IR), 50 mg/kg p-CA with R-IR (p-CA 50), and 100 mg/kg p-CA with R-IR (p-CA 100). After the dorsum of all rats was opened and the right nephrectomy was performed, all groups except sham were clamped on the left renal artery and ischemia and reperfusion protocol was performed. P-CA was administered in two doses, 60 min before ischemia and 30 min before reperfusion. Total antioxidant levels (TAS), total oxidant level (TOS), superoxide dismutase (SOD), malondialdehyde (MDA), and myeloperoxidase (MPO) levels of left kidney were measured spectrophotometrically, and oxidative stress index (OSI) was calculated.Results TOS, MDA, MPO, and OSI values increased in R-IR group compared to S (p <0.01), while TAS and SOD values decreased. Increase in TAS and SOD values, a decrease in TOS, MDA, MPO, and OSI values were observed in P-CA applied groups (p <0.05).Conclusion Our fi ndings indicate that p-CA administration in renal ischemia-reperfusion injury may play a role in protecting tissue by reducing oxidant damage.
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